{"title":"Expression of concern “cross sections of the 226Ra(p,xn) reactions relevant for 225Ac production“","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109598"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.nucmedbio.2025.109594
Siran Qian, Surendra Reddy Gundam, Carol Garcia, Shihong Li, Hsiaoju Lee, Jay S. Wright
Positron emission tomography (PET) fluorine-18 radiosynthesis primarily relies on operationally robust, albeit scope-limited methodologies. Therefore, a marked scientific need remains for new PET-compatible labelling protocols to expand radiochemical space. In this context, α-fluoroamides are a well-established motif in drug molecules that have yet to be extensively adopted for fluorine-18 PET. Accordingly, this Article describes the nucleophilic substitution of amide α-C–H bonds with (radio)fluoride via base-mediated cyclisation of N-sulphonyloxyamides under conditions conducive to PET production. Radiolabelling proceeds with excellent radiochemical conversions (RCC, up to 91%), radiochemical purities (RCP, up to >99%), isolated radiochemical yields (RCY, up to 23%), and molar activities (Am, up to 85.1 GBq/μmol) under manual and fully automated conditions. Divergent access to 19F-standards for imaging agent characterisation is efficiently realised under an analogous protocol, which was modified to selectively deliver α-lactams (aziridinones) with unprecedented resistance to decomposition. A fluorination mechanism involving NO scission, lactamisation, and strain-release-driven CN ionisation is proposed. These protocols provide a versatile platform for the radiosynthesis of fluoroamides with high PET production utility.
{"title":"C–H (radio)fluorination of hydroxamides via strained and electronically tunable α-lactams enabled by N–O scission","authors":"Siran Qian, Surendra Reddy Gundam, Carol Garcia, Shihong Li, Hsiaoju Lee, Jay S. Wright","doi":"10.1016/j.nucmedbio.2025.109594","DOIUrl":"10.1016/j.nucmedbio.2025.109594","url":null,"abstract":"<div><div>Positron emission tomography (PET) fluorine-18 radiosynthesis primarily relies on operationally robust, albeit scope-limited methodologies. Therefore, a marked scientific need remains for new PET-compatible labelling protocols to expand radiochemical space. In this context, α-fluoroamides are a well-established motif in drug molecules that have yet to be extensively adopted for fluorine-18 PET. Accordingly, this Article describes the nucleophilic substitution of amide α-C–H bonds with (radio)fluoride via base-mediated cyclisation of <em>N</em>-sulphonyloxyamides under conditions conducive to PET production. Radiolabelling proceeds with excellent radiochemical conversions (RCC, up to 91%), radiochemical purities (RCP, up to >99%), isolated radiochemical yields (RCY, up to 23%), and molar activities (A<sub>m</sub>, up to 85.1 GBq/μmol) under manual and fully automated conditions. Divergent access to <sup>19</sup>F-standards for imaging agent characterisation is efficiently realised under an analogous protocol, which was modified to selectively deliver α-lactams (aziridinones) with unprecedented resistance to decomposition. A fluorination mechanism involving N<img>O scission, lactamisation, and strain-release-driven C<img>N ionisation is proposed. These protocols provide a versatile platform for the radiosynthesis of fluoroamides with high PET production utility.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109594"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.nucmedbio.2025.109601
Jordy Akkermans , Alan Miranda , Jeroen Verhaeghe , Filipe Elvas , Franziska Zajicek , Jonathan Bard , Longbin Liu , Vinod Khetarpal , Robert Doot , Steven Staelens , Daniele Bertoglio
Background
Huntington's disease is a neurodegenerative condition resulting from an expanded CAG repeat in the huntingtin gene that produces a mutant form of the huntingtin protein (mHTT). In this study we estimated the radiation safety of two structurally related mHTT radioligands, [18F]CHDI-385 and [18F]CHDI-386, by evaluating the in vivo and ex vivo dosimetry of both radioligands using CD-1 Swiss mice.
Methods
We used adult male and female CD-1 Swiss mice (n = 15 per sex/radioligand) to assess in vivo positron emission tomography/computed tomography (PET/CT) imaging-based and ex vivo biodistribution-based tracer distribution of the radioligands at 30-, 60-, 120-, 240-, and 360-min post-radioligand injection. Organ activity was quantified, and the residence time was extrapolated to human phantoms. The absorbed and effective doses were estimated using OLINDA/EXM 2.2 and IDAC-Dose2.1.
Results
Both radioligands, [18F]CHDI-385 and [18F]CHDI-386, showed high uptake in the gallbladder and urinary bladder, with a slow washout in most organs. The colon wall received the highest equivalent organ dose for both modalities. Ex vivo effective dose estimates were 15.4 μSv/MBq for [18F]CHDI-385 and 16.3 μSv/MBq for [18F]CHDI-386, while in vivo effective dose estimates were 18.5 μSv/MBq and 18.7 μSv/MBq, respectively.
Conclusion
[18F]CHDI-385 and [18F]CHDI-386 dosimetry results showed absorbed and effective doses in acceptable range and below the recommended limits. An injection of 370 MBq (10 mCi) in humans is estimated to result in highest (in vivo) effective doses of 6.85 mSv for [18F]CHDI-385 and 6.92 mSv for [18F]CHDI-386.
{"title":"Rodent biodistribution and dosimetry of the PET radioligands [18F]CHDI-385 and [18F]CHDI-386 targeting mutant huntingtin aggregates","authors":"Jordy Akkermans , Alan Miranda , Jeroen Verhaeghe , Filipe Elvas , Franziska Zajicek , Jonathan Bard , Longbin Liu , Vinod Khetarpal , Robert Doot , Steven Staelens , Daniele Bertoglio","doi":"10.1016/j.nucmedbio.2025.109601","DOIUrl":"10.1016/j.nucmedbio.2025.109601","url":null,"abstract":"<div><h3>Background</h3><div>Huntington's disease is a neurodegenerative condition resulting from an expanded CAG repeat in the huntingtin gene that produces a mutant form of the huntingtin protein (mHTT). In this study we estimated the radiation safety of two structurally related mHTT radioligands, [<sup>18</sup>F]CHDI-385 and [<sup>18</sup>F]CHDI-386, by evaluating the <em>in vivo</em> and <em>ex vivo</em> dosimetry of both radioligands using CD-1 Swiss mice.</div></div><div><h3>Methods</h3><div>We used adult male and female CD-1 Swiss mice (<em>n</em> = 15 per sex/radioligand) to assess <em>in vivo</em> positron emission tomography/computed tomography (PET/CT) imaging-based and <em>ex vivo</em> biodistribution-based tracer distribution of the radioligands at 30-, 60-, 120-, 240-, and 360-min post-radioligand injection. Organ activity was quantified, and the residence time was extrapolated to human phantoms. The absorbed and effective doses were estimated using OLINDA/EXM 2.2 and IDAC-Dose2.1.</div></div><div><h3>Results</h3><div>Both radioligands, [<sup>18</sup>F]CHDI-385 and [<sup>18</sup>F]CHDI-386, showed high uptake in the gallbladder and urinary bladder, with a slow washout in most organs. The colon wall received the highest equivalent organ dose for both modalities. <em>Ex vivo</em> effective dose estimates were 15.4 μSv/MBq for [<sup>18</sup>F]CHDI-385 and 16.3 μSv/MBq for [<sup>18</sup>F]CHDI-386, while <em>in vivo</em> effective dose estimates were 18.5 μSv/MBq and 18.7 μSv/MBq, respectively.</div></div><div><h3>Conclusion</h3><div>[<sup>18</sup>F]CHDI-385 and [<sup>18</sup>F]CHDI-386 dosimetry results showed absorbed and effective doses in acceptable range and below the recommended limits. An injection of 370 MBq (10 mCi) in humans is estimated to result in highest (<em>in vivo</em>) effective doses of 6.85 mSv for [<sup>18</sup>F]CHDI-385 and 6.92 mSv for [<sup>18</sup>F]CHDI-386.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109601"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.nucmedbio.2025.109596
Michael R. Lewis , Claudia G. Chambers , Maryam Heidari-Kharaji , Kanishka Sikligar , Vivian A. Yang , Alexander W. Schaedler , Mojgan Golzy , Lisa D. Watkinson , Terry L. Carmack , Joni M. Lunceford , Colleen Garrett , Christos Papageorgiou , Jessica L. Talbott , Charles A. Maitz , Jeffrey N. Bryan , Charles J. Smith
Background
In the United States, breast cancer is the second leading cause of cancer-related death. Triple-negative breast cancer (TNBC) is of substantial concern, as it lacks the receptors usually targeted by conventional treatments. Triple-negative breast tumors have a high degree of copper metabolism for the synthesis of transporters, enzymes, and chaperones. Tetrathiomolybdate (TM) is a well-tolerated oral therapy that has been investigated for chelating copper from tumors in TNBC patients, resulting in extended remission. The overall goal of this research was to evaluate [64Cu]CuCl2 PET/CT imaging of copper utilization in this disease, in the presence and absence of TM.
Methods
Uptake, internalization, and efflux studies were performed in TNBC cells versus normal cells. Biodistribution experiments were then conducted in TNBC xenograft-bearing mice that were administered TM versus controls. PET/CT imaging of mice carrying TNBC tumors was also performed in the presence and absence of TM. Finally, imaging was performed in a healthy cat and in a cat with mammary carcinoma.
Results
SUM149 TNBC cells selectively took up, internalized, and retained [64Cu]CuCl2 more avidly than normal fibroblasts. When SUM149-bearing mice were given TM, tumor uptake decreased and tracer accumulation shifted predominantly to the liver and kidneys, compared to control mice, in which large quantities of 64Cu were excreted into the intestines. These results were supported by PET/CT imaging of the mice. PET/CT of companion cats gave results similar to those obtained in mice, with high accumulation of radioactivity observed in the liver and gallbladder and moderate intestinal and renal clearance. In a cat with mammary carcinoma, tumor uptake of [64Cu]CuCl2 was highly conspicuous, even in close proximity to the liver.
Conclusions
Utilization of [64Cu]CuCl2 in triple-negative breast cancer can be detected efficiently in cell and animal models of this disease. The tracer was also used successfully to evaluate TM administration in the SUM149 TNBC mouse model. Furthermore, PET/CT imaging of both mice and cats with breast cancer shows the potential to monitor treatment with TM in a facile, noninvasive manner. We are currently conducting a clinical trial of [64Cu]CuCl2 PET/CT in companion cats with mammary carcinoma, with the future goal of evaluating the efficacy of TM in feline patients.
{"title":"PET imaging of [64Cu]copper(II) chloride and tetrathiomolybdate administration in animal models of triple-negative breast cancer","authors":"Michael R. Lewis , Claudia G. Chambers , Maryam Heidari-Kharaji , Kanishka Sikligar , Vivian A. Yang , Alexander W. Schaedler , Mojgan Golzy , Lisa D. Watkinson , Terry L. Carmack , Joni M. Lunceford , Colleen Garrett , Christos Papageorgiou , Jessica L. Talbott , Charles A. Maitz , Jeffrey N. Bryan , Charles J. Smith","doi":"10.1016/j.nucmedbio.2025.109596","DOIUrl":"10.1016/j.nucmedbio.2025.109596","url":null,"abstract":"<div><h3>Background</h3><div>In the United States, breast cancer is the second leading cause of cancer-related death. Triple-negative breast cancer (TNBC) is of substantial concern, as it lacks the receptors usually targeted by conventional treatments. Triple-negative breast tumors have a high degree of copper metabolism for the synthesis of transporters, enzymes, and chaperones. Tetrathiomolybdate (TM) is a well-tolerated oral therapy that has been investigated for chelating copper from tumors in TNBC patients, resulting in extended remission. The overall goal of this research was to evaluate [<sup>64</sup>Cu]CuCl<sub>2</sub> PET/CT imaging of copper utilization in this disease, in the presence and absence of TM.</div></div><div><h3>Methods</h3><div>Uptake, internalization, and efflux studies were performed in TNBC cells versus normal cells. Biodistribution experiments were then conducted in TNBC xenograft-bearing mice that were administered TM versus controls. PET/CT imaging of mice carrying TNBC tumors was also performed in the presence and absence of TM. Finally, imaging was performed in a healthy cat and in a cat with mammary carcinoma.</div></div><div><h3>Results</h3><div>SUM149 TNBC cells selectively took up, internalized, and retained [<sup>64</sup>Cu]CuCl<sub>2</sub> more avidly than normal fibroblasts. When SUM149-bearing mice were given TM, tumor uptake decreased and tracer accumulation shifted predominantly to the liver and kidneys, compared to control mice, in which large quantities of <sup>64</sup>Cu were excreted into the intestines. These results were supported by PET/CT imaging of the mice. PET/CT of companion cats gave results similar to those obtained in mice, with high accumulation of radioactivity observed in the liver and gallbladder and moderate intestinal and renal clearance. In a cat with mammary carcinoma, tumor uptake of [<sup>64</sup>Cu]CuCl<sub>2</sub> was highly conspicuous, even in close proximity to the liver.</div></div><div><h3>Conclusions</h3><div>Utilization of [<sup>64</sup>Cu]CuCl<sub>2</sub> in triple-negative breast cancer can be detected efficiently in cell and animal models of this disease. The tracer was also used successfully to evaluate TM administration in the SUM149 TNBC mouse model. Furthermore, PET/CT imaging of both mice and cats with breast cancer shows the potential to monitor treatment with TM in a facile, noninvasive manner. We are currently conducting a clinical trial of [<sup>64</sup>Cu]CuCl<sub>2</sub> PET/CT in companion cats with mammary carcinoma, with the future goal of evaluating the efficacy of TM in feline patients.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109596"},"PeriodicalIF":3.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Scandium-47 (47Sc), a medium-energy β− emitter with a half-life of 3.35 days and associated γ emission (159 keV, 68.1 %), is an attractive radionuclide for targeted radionuclide therapy and theranostics. Production of 47Sc via neutron irradiation of enriched 46Ca targets through the 46Ca(n,γ)47Ca → 47Sc decay pathway offers advantages such as thermal neutron utilisation and minimised contaminant co-production. Efficient separation and repeated recovery of 47Sc in a quasi-generator system are crucial for enabling its medical application.
Results
Neutron irradiations of calcium carbonate targets 46Ca-enriched (5.2 % and 10.5 %) at the Maria research reactor yielded up to 5.18 GBq 47Sc and 5.60 GBq 47Ca at the end of bombardment. Separation of 47Sc from 47Ca was performed using DGA resin with recovery efficiencies of 81–97 % for 47Sc and 98–99 % for 47Ca in up to five consecutive elutions within 18 days. Radiochemical purity of eluted [47Sc]ScCl3 exceeded 95 % in initial separations. Radiolabelling studies with DOTA-TATE demonstrated effective molar activities up to 20 MBq/nmol and radiochemical purities >98 %. Stability tests confirmed that the [47Sc]ScCl3 eluate remained suitable for radiolabelling for the entire testing period of up to 4 days post-elution. Trace metal analysis showed predominantly low contamination levels, with sporadic impurities attributed to handling conditions.
Conclusions
The 47Ca/47Sc quasi-generator system based on neutron irradiation of enriched 46Ca targets offers a reliable source of high-quality 47Sc for radiopharmaceutical applications. Multiple elutions from a single target enable sustained production of 47Sc with excellent radionuclidic and radiochemical purity. These results support further development of 47Sc as a theranostic radionuclide for larger-scale production. A preliminary specification for 47Sc as a radionuclide precursor was proposed following the European Pharmacopoeia guidelines, providing a groundwork for future standardisation.
{"title":"Scandium-47 as a radionuclide precursor: Feasibility of production in a 47Ca/47Sc generator-like system","authors":"Izabela Cieszykowska, Małgorzata Żółtowska, Dariusz Pawlak, Łukasz Sochaczewski, Zbigniew Tymiński, Justyna Marganiec-Gałązka, Renata Mikołajczak","doi":"10.1016/j.nucmedbio.2025.109595","DOIUrl":"10.1016/j.nucmedbio.2025.109595","url":null,"abstract":"<div><h3>Background</h3><div>Scandium-47 (<sup>47</sup>Sc), a medium-energy β<sup>−</sup> emitter with a half-life of 3.35 days and associated γ emission (159 keV, 68.1 %), is an attractive radionuclide for targeted radionuclide therapy and theranostics. Production of <sup>47</sup>Sc via neutron irradiation of enriched <sup>46</sup>Ca targets through the <sup>46</sup>Ca(n,γ)<sup>47</sup>Ca → <sup>47</sup>Sc decay pathway offers advantages such as thermal neutron utilisation and minimised contaminant co-production. Efficient separation and repeated recovery of <sup>47</sup>Sc in a quasi-generator system are crucial for enabling its medical application.</div></div><div><h3>Results</h3><div>Neutron irradiations of calcium carbonate targets <sup>46</sup>Ca-enriched (5.2 % and 10.5 %) at the Maria research reactor yielded up to 5.18 GBq <sup>47</sup>Sc and 5.60 GBq <sup>47</sup>Ca at the end of bombardment. Separation of <sup>47</sup>Sc from <sup>47</sup>Ca was performed using DGA resin with recovery efficiencies of 81–97 % for <sup>47</sup>Sc and 98–99 % for <sup>47</sup>Ca in up to five consecutive elutions within 18 days. Radiochemical purity of eluted [<sup>47</sup>Sc]ScCl<sub>3</sub> exceeded 95 % in initial separations. Radiolabelling studies with DOTA-TATE demonstrated effective molar activities up to 20 MBq/nmol and radiochemical purities >98 %. Stability tests confirmed that the [<sup>47</sup>Sc]ScCl<sub>3</sub> eluate remained suitable for radiolabelling for the entire testing period of up to 4 days post-elution. Trace metal analysis showed predominantly low contamination levels, with sporadic impurities attributed to handling conditions.</div></div><div><h3>Conclusions</h3><div>The <sup>47</sup>Ca/<sup>47</sup>Sc quasi-generator system based on neutron irradiation of enriched <sup>46</sup>Ca targets offers a reliable source of high-quality <sup>47</sup>Sc for radiopharmaceutical applications. Multiple elutions from a single target enable sustained production of <sup>47</sup>Sc with excellent radionuclidic and radiochemical purity. These results support further development of <sup>47</sup>Sc as a theranostic radionuclide for larger-scale production. A preliminary specification for <sup>47</sup>Sc as a radionuclide precursor was proposed following the European Pharmacopoeia guidelines, providing a groundwork for future standardisation.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109595"},"PeriodicalIF":3.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.nucmedbio.2025.109597
Cyril O.Y. Fong , Ejike V. Iweha , Fabio Gallazzi , Anupam Mathur , Olivia Heyne , Jodi Mootz , Madison Mayher , David S. Tatum , Darren Magda , Carolyn J. Anderson
<div><div>There is a need for chelators that are versatile for complexing multiple radiometals. We previously demonstrated that the macrocyclic 1,2-HOPO chelator, L804, has utility for complexing <sup>177</sup>Lu(III) for radiopharmaceutical therapy and <sup>89</sup>Zr(IV) for PET imaging with antibody-based agents. Here, we investigated whether <sup>89</sup>Zr-radiolabelled peptidomimetic LLP2A could function as a diagnostic surrogate for [<sup>177</sup>Lu]Lu-LLP2A therapy in the targeting of VLA-4 overexpressed in melanoma, with and without an albumin-binding moiety (pIBA) for biological half-life extension.</div></div><div><h3>Methods</h3><div>L804-LLP2A (<strong>1</strong>) and L804-pIBA-LLP2A (<strong>2</strong>) were synthesized and radiolabelled with <sup>89</sup>Zr and <sup>177</sup>Lu. Distribution coefficients, in vitro binding affinity, biodistribution, and PET/SPECT imaging data in the B16F10 tumor-bearing mice model of metastatic melanoma were collected.</div></div><div><h3>Results</h3><div>Quantitative radiochemical yield (>99 %) was achieved with <sup>89</sup>Zr and <sup>177</sup>Lu within 30 min at 25 °C. Through a shake flask method, the LogD<sub>7.4</sub> distribution coefficients of [<sup>89</sup>Zr]Zr-<strong>2</strong> and [<sup>177</sup>Lu]Lu-<strong>2</strong> (−0.67 ± 0.06 and − 1.05 ± 0.10, respectively) indicated greater lipophilicity compared to their non-albumin binder containing analogues, [<sup>89</sup>Zr]Zr-<strong>1</strong> and [<sup>177</sup>Lu]Lu-<strong>1</strong> (−1.67 ± 0.19 and − 1.26 ± 0.12, respectively). The addition of pIBA to the tracer scaffold did not appreciably affect binding affinity of <sup>89</sup>Zr- or <sup>177</sup>Lu-labeled LLP2A to VLA-4, with the K<sub>d</sub> values for [<sup>89</sup>Zr]Zr-<strong>1</strong> vs [<sup>89</sup>Zr]Zr-<strong>2</strong> (2.2 ± 0.2 vs 1.6 ± 0.2 nM) and [<sup>177</sup>Lu]Lu-<strong>1</strong> vs [<sup>177</sup>Lu]Lu-<strong>2</strong> (8.4 ± 1.0 vs 10.8 ± 2.6 nM) being comparable. In B16F10 melanoma tumor-bearing mice, both [<sup>89</sup>Zr]Zr-<strong>1</strong> and [<sup>177</sup>Lu]Lu-<strong>1</strong> exhibited rapid blood clearance but had distinctly different biodistribution profiles. [<sup>89</sup>Zr]Zr-<strong>1</strong> was retained more in the tumor, kidney, and spleen out to 48 h compared to [<sup>177</sup>Lu]Lu-<strong>1</strong>. There was a rapid clearance from both tumor and normal tissues for [<sup>177</sup>Lu]Lu-<strong>1</strong> out to 48 h, and aside from the muscle, tumor: non-tumor ratios were overall greater for [<sup>177</sup>Lu]Lu-<strong>1</strong> than those obtained for [<sup>89</sup>Zr]Zr-<strong>1</strong>. The albumin-binding [<sup>89</sup>Zr]Zr-<strong>2</strong> and [<sup>177</sup>Lu]Lu-<strong>2</strong> displayed more similar distribution profiles, with higher tumor and non-tumor tissue accumulation, and significantly slower blood clearance. Both tracers gradually cleared out of tumor and non-tumor tissues, although [<sup>
需要一种多功能的螯合剂来络合多种放射性金属。我们之前已经证明，大环1,2- hopo螯合剂L804可与177Lu（III）和89Zr（IV）配合使用，用于放射性药物治疗和基于抗体的PET成像。在这里，我们研究了89zr放射标记的拟肽LLP2A是否可以作为[177Lu]Lu-LLP2A治疗的诊断替代品，用于靶向黑色素瘤中过表达的vla4，无论是否具有白蛋白结合片段（pIBA）以延长生物半衰期。方法合成L804-LLP2A(1)和L804-pIBA-LLP2A(2)，分别用89Zr和177Lu进行放射性标记。收集B16F10荷瘤小鼠转移性黑色素瘤模型的分布系数、体外结合亲和力、生物分布及PET/SPECT成像数据。结果：在25°C条件下，89Zr和177Lu在30 min内获得了定量放射化学产率（> 99%）。通过摇瓶法，[89Zr]Zr-2和[177Lu]Lu-2的LogD7.4分布系数（分别为-0.67±0.06和- 1.05±0.10）表明，与不含白蛋白的类似物[89Zr]Zr-1和[177Lu]Lu-1相比，[89Zr]Zr-1和[177Lu]Lu-1的亲脂性更强（分别为-1.67±0.19和- 1.26±0.12）。在示色支架中添加pIBA对89Zr-或177Lu-标记的LLP2A与vla4的结合亲和力没有明显影响，[89Zr]Zr-1与[89Zr]Zr-2的Kd值（2.2±0.2 vs 1.6±0.2 nM）和[177Lu]Lu-1与[177Lu]Lu-2的Kd值（8.4±1.0 vs 10.8±2.6 nM）相当。在B16F10黑色素瘤荷瘤小鼠中，[89Zr]Zr-1和[177Lu]Lu-1均表现出快速的血液清除，但具有明显不同的生物分布谱。与[177Lu]Lu-1相比，[89Zr]Zr-1在肿瘤、肾脏和脾脏中保留的时间长达48 h。在48小时内，[177Lu]Lu-1在肿瘤和正常组织中的清除速度都很快，除肌肉外，[177Lu]Lu-1的肿瘤：非肿瘤比例总体上高于[89Zr]Zr-1。白蛋白结合的[89Zr]Zr-2和[177Lu] Zr-2的分布更为相似，肿瘤组织和非肿瘤组织积累量更高，血液清除率明显较慢。两种示踪剂逐渐从肿瘤组织和非肿瘤组织中清除，尽管与[177Lu]Lu-2相比，[89Zr]Zr-2在96 h时在肾脏和肿瘤中的滞留略多。结论：与不含pIBA的类似物相比，在LLP2A中添加pIBA导致[89Zr]Zr-2和[177Lu]Lu-2之间的分布曲线相似，其中89Zr和177Lu药物表现出明显不同的生物分布，表明白蛋白结合片段对使用这些化学上不同的同位素匹配的小分子治疗对有益。
{"title":"Matched pair suitability of 89Zr and 177Lu-labeled L804-LLP2A theranostics for targeting VLA-4 in melanoma","authors":"Cyril O.Y. Fong , Ejike V. Iweha , Fabio Gallazzi , Anupam Mathur , Olivia Heyne , Jodi Mootz , Madison Mayher , David S. Tatum , Darren Magda , Carolyn J. Anderson","doi":"10.1016/j.nucmedbio.2025.109597","DOIUrl":"10.1016/j.nucmedbio.2025.109597","url":null,"abstract":"<div><div>There is a need for chelators that are versatile for complexing multiple radiometals. We previously demonstrated that the macrocyclic 1,2-HOPO chelator, L804, has utility for complexing <sup>177</sup>Lu(III) for radiopharmaceutical therapy and <sup>89</sup>Zr(IV) for PET imaging with antibody-based agents. Here, we investigated whether <sup>89</sup>Zr-radiolabelled peptidomimetic LLP2A could function as a diagnostic surrogate for [<sup>177</sup>Lu]Lu-LLP2A therapy in the targeting of VLA-4 overexpressed in melanoma, with and without an albumin-binding moiety (pIBA) for biological half-life extension.</div></div><div><h3>Methods</h3><div>L804-LLP2A (<strong>1</strong>) and L804-pIBA-LLP2A (<strong>2</strong>) were synthesized and radiolabelled with <sup>89</sup>Zr and <sup>177</sup>Lu. Distribution coefficients, in vitro binding affinity, biodistribution, and PET/SPECT imaging data in the B16F10 tumor-bearing mice model of metastatic melanoma were collected.</div></div><div><h3>Results</h3><div>Quantitative radiochemical yield (>99 %) was achieved with <sup>89</sup>Zr and <sup>177</sup>Lu within 30 min at 25 °C. Through a shake flask method, the LogD<sub>7.4</sub> distribution coefficients of [<sup>89</sup>Zr]Zr-<strong>2</strong> and [<sup>177</sup>Lu]Lu-<strong>2</strong> (−0.67 ± 0.06 and − 1.05 ± 0.10, respectively) indicated greater lipophilicity compared to their non-albumin binder containing analogues, [<sup>89</sup>Zr]Zr-<strong>1</strong> and [<sup>177</sup>Lu]Lu-<strong>1</strong> (−1.67 ± 0.19 and − 1.26 ± 0.12, respectively). The addition of pIBA to the tracer scaffold did not appreciably affect binding affinity of <sup>89</sup>Zr- or <sup>177</sup>Lu-labeled LLP2A to VLA-4, with the K<sub>d</sub> values for [<sup>89</sup>Zr]Zr-<strong>1</strong> vs [<sup>89</sup>Zr]Zr-<strong>2</strong> (2.2 ± 0.2 vs 1.6 ± 0.2 nM) and [<sup>177</sup>Lu]Lu-<strong>1</strong> vs [<sup>177</sup>Lu]Lu-<strong>2</strong> (8.4 ± 1.0 vs 10.8 ± 2.6 nM) being comparable. In B16F10 melanoma tumor-bearing mice, both [<sup>89</sup>Zr]Zr-<strong>1</strong> and [<sup>177</sup>Lu]Lu-<strong>1</strong> exhibited rapid blood clearance but had distinctly different biodistribution profiles. [<sup>89</sup>Zr]Zr-<strong>1</strong> was retained more in the tumor, kidney, and spleen out to 48 h compared to [<sup>177</sup>Lu]Lu-<strong>1</strong>. There was a rapid clearance from both tumor and normal tissues for [<sup>177</sup>Lu]Lu-<strong>1</strong> out to 48 h, and aside from the muscle, tumor: non-tumor ratios were overall greater for [<sup>177</sup>Lu]Lu-<strong>1</strong> than those obtained for [<sup>89</sup>Zr]Zr-<strong>1</strong>. The albumin-binding [<sup>89</sup>Zr]Zr-<strong>2</strong> and [<sup>177</sup>Lu]Lu-<strong>2</strong> displayed more similar distribution profiles, with higher tumor and non-tumor tissue accumulation, and significantly slower blood clearance. Both tracers gradually cleared out of tumor and non-tumor tissues, although [<sup>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109597"},"PeriodicalIF":3.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sodium–glucose co-transporters (SGLTs), particularly SGLT1 and SGLT2, play an active role in glucose uptake by cancer cells and have gained attention as novel therapeutic targets. However, the development of nuclear medicine imaging agents specific to SGLTs has not yet been explored. This study aimed to develop and evaluate radiolabeled glycoside derivatives targeting SGLT1 and SGLT2 for cancer imaging.
Methods
β-Arbutin, a structural analog of methyl-α-D-glucopyranoside (MDG) which is SGLTs substrate, and phlorizin, a SGLT2 inhibitor, were selected as glycoside compounds for radioiodination, [125I]β-arbutin and [125I]phlorizin were synthesized. The accumulation was measured in HEK293 cells transfected overexpress GLUT1, GLUT3, SGLT1, or SGLT2. Subsequent accumulation studies were conducted in LS180 and DLD-1 cancer cell lines, and the gene expression levels were quantified by real-time polymerase chain reaction (PCR). Biodistribution of both radiotracers was examined in tumor-bearing mice.
Results
[125I]β-Arbutin had affinity for SGLT1 and SGLT2, whereas [125I]phlorizin had affinity for SGLT1 and GLUT3. [125I]β-Arbutin accumulated preferentially in SGLT1-high LS180 cells, whereas [125I]phlorizin accumulated in GLUT3-high DLD-1 cells. In vivo, [125I]β-arbutin exhibited favorable biodistribution with low brain and thyroid accumulation, rapid blood clearance, and high tumor-to-blood ratios in SGLT1-expressing tumors. Although [125I]phlorizin also showed low brain and thyroid accumulation, its blood clearance was slower and tumor-to-blood ratios were lower.
Conclusion
[125I]β-Arbutin is a promising radiopharmaceutical candidate for imaging cancers with high SGLTs expression.
钠-葡萄糖共转运体（sglt），特别是SGLT1和SGLT2，在癌细胞的葡萄糖摄取中发挥积极作用，并作为新的治疗靶点受到关注。然而，针对sglt的核医学显像剂的开发尚未探索。本研究旨在开发和评估靶向SGLT1和SGLT2的放射性标记糖苷衍生物用于癌症成像。方法选择SGLTs底物甲基α- d -葡萄糖吡喃苷（MDG）的结构类似物β-杨梅苷（β-arbutin）和SGLT2抑制剂苯根苷（phlorizin）作为放射性碘化的苷类化合物，合成[125I]β-杨梅苷和[125I]苯根苷。在转染过表达GLUT1、GLUT3、SGLT1或SGLT2的HEK293细胞中测量这种积累。随后在LS180和DLD-1癌细胞中进行积累研究，并通过实时聚合酶链反应（PCR）测定基因表达水平。研究了两种示踪剂在荷瘤小鼠体内的生物分布。结果[125I]β-熊果苷对SGLT1和SGLT2具有亲和力，而[125I]根连素对SGLT1和GLUT3具有亲和力。[125I]β-熊果苷优先在sglt1高的LS180细胞中积累，而[125I]根霉素在glut3高的DLD-1细胞中积累。在体内，[125I]β-熊果苷表现出良好的生物分布，在表达sglt1的肿瘤中具有低脑和甲状腺积聚、快速血液清除和高肿瘤-血液比率的特点。虽然[125I]苯连菌素在脑和甲状腺的蓄积也较低，但其血液清除率较慢，肿瘤与血液比率较低。结论[125I]β-熊果苷是一种很有前途的用于SGLTs高表达肿瘤显像的放射性药物候选物。
{"title":"Development of glycoside-based nuclear medicine imaging agents for the sodium–glucose co-transporters in cancer cells","authors":"Kakeru Sato , Ririka Handa , Jianwei Yao , Jinya Higashino , Taiga Watanabe , Ryotaro Abe , Yuna Hamada , Jundai Yamagata , Yuma Momose , Asuka Mizutani , Masato Kobayashi , Ryuichi Nishii , Keiichi Kawai","doi":"10.1016/j.nucmedbio.2025.109591","DOIUrl":"10.1016/j.nucmedbio.2025.109591","url":null,"abstract":"<div><h3>Introduction</h3><div>Sodium–glucose co-transporters (SGLTs), particularly SGLT1 and SGLT2, play an active role in glucose uptake by cancer cells and have gained attention as novel therapeutic targets. However, the development of nuclear medicine imaging agents specific to SGLTs has not yet been explored. This study aimed to develop and evaluate radiolabeled glycoside derivatives targeting SGLT1 and SGLT2 for cancer imaging.</div></div><div><h3>Methods</h3><div>β-Arbutin, a structural analog of methyl-α-D-glucopyranoside (MDG) which is SGLTs substrate, and phlorizin, a SGLT2 inhibitor, were selected as glycoside compounds for radioiodination, [<sup>125</sup>I]β-arbutin and [<sup>125</sup>I]phlorizin were synthesized. The accumulation was measured in HEK293 cells transfected overexpress GLUT1, GLUT3, SGLT1, or SGLT2. Subsequent accumulation studies were conducted in LS180 and DLD-1 cancer cell lines, and the gene expression levels were quantified by real-time polymerase chain reaction (PCR). Biodistribution of both radiotracers was examined in tumor-bearing mice.</div></div><div><h3>Results</h3><div>[<sup>125</sup>I]β-Arbutin had affinity for SGLT1 and SGLT2, whereas [<sup>125</sup>I]phlorizin had affinity for SGLT1 and GLUT3. [<sup>125</sup>I]β-Arbutin accumulated preferentially in SGLT1-high LS180 cells, whereas [<sup>125</sup>I]phlorizin accumulated in GLUT3-high DLD-1 cells. <em>In vivo</em>, [<sup>125</sup>I]β-arbutin exhibited favorable biodistribution with low brain and thyroid accumulation, rapid blood clearance, and high tumor-to-blood ratios in SGLT1-expressing tumors. Although [<sup>125</sup>I]phlorizin also showed low brain and thyroid accumulation, its blood clearance was slower and tumor-to-blood ratios were lower.</div></div><div><h3>Conclusion</h3><div>[<sup>125</sup>I]β-Arbutin is a promising radiopharmaceutical candidate for imaging cancers with high SGLTs expression.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109591"},"PeriodicalIF":3.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-17DOI: 10.1016/j.nucmedbio.2025.109581
Jaime D. Mondragon , Sofia Marcolini , Bruno Lima Giacobbo , Philip H. Elsinga , Rudi A.J.O. Dierckx , Marleen Tollenaere , Debby van Dam , Peter P. De Deyn
Background
The locus coeruleus (LC) and its noradrenergic projections are among the earliest sites displaying pathology in Alzheimer's disease (AD) and Parkinson's disease (PD). In vivo measures of norepinephrine transporter (NET) availability with [11C]methylreboxetine ([11C]MRB) positron emission tomography (PET) and structural magnetic resonance imaging (MRI) indices of LC integrity provide complementary, but rarely integrated biomarkers.
Methods
13 Healthy controls (HC), individuals with 12 AD or amnestic mild cognitive impairment due to AD (AD/aMCI), and 5 patients with PD underwent [11C]MRB PET and high-resolution T1-weighted MRI. NET availability was quantified using [11C]MRB PET SUV-ratio–based binding potential (SUVr-BP) in the LC and projection regions (hippocampus, amygdala, thalamus, and prefrontal cortex). LC structural integrity was indexed by LC MRI contrast-to-noise ratio (CNR), and projection region volumes were extracted with FreeSurfer. Group differences were assessed with Kruskal–Wallis tests, and PET–MRI associations were examined using Pearson correlations with Yeo–Johnson transformation to reduce outlier influence.
Results
No significant group-level differences in [11C]MRB PET SUVr-BP or MRI measures were observed across HC, AD/aMCI, and PD. However, LC [11C]MRB PET SUVr-BP correlated with LC MRI-CNR (r = 0.429, 95 % CI [0.082–0.684], p = 0.018). In contrast, PET–MRI associations in projection regions were weak and non-significant. Exploratory analyses confirmed expected differences in cognition, neuropsychiatric symptoms, and functional measures, most pronounced in AD/aMCI participants.
Conclusions
This proof-of-concept study demonstrates convergent multimodal assessment of LC integrity using [11C]MRB PET and LC MRI-CNR, whereas projection regions showed divergent or absent associations. These findings highlight the potential of the LC as a target for multimodal biomarker development and support further investigation of these imaging strategies in larger, longitudinal cohorts to delineate their role in detecting noradrenergic vulnerability in neurodegeneration.
Significance statement
This study integrates [11C]MRB PET and MRI to examine noradrenergic integrity in Alzheimer's and Parkinson's disease. Results demonstrate strong PET–MRI convergence in the locus coeruleus, but not in projection regions, highlighting the locus coeruleus as a sensitive biomarker target and supporting multimodal imaging approaches for early detection of neurodegenerative vulnerability.
蓝斑（LC）及其去肾上腺素能投射是阿尔茨海默病（AD）和帕金森病（PD）中最早显示病理的部位之一。体内测量去甲肾上腺素转运体（NET）可用性与[11C]甲基瑞波西汀（[11C]MRB）正电子发射断层扫描（PET）和结构磁共振成像（MRI）的LC完整性指标提供互补，但很少整合的生物标志物。方法对13例健康对照（HC）、12例AD或AD所致遗忘性轻度认知障碍患者（AD/aMCI）和5例PD患者进行[11C]MRB PET和高分辨率t1加权MRI检查。使用[11C]MRB PET基于suv比率的结合电位（SUVr-BP）在LC和投射区（海马、杏仁核、丘脑和前额皮质）量化NET可用性。LC MRI对比噪声比（CNR）对LC结构完整性进行索引，并用FreeSurfer提取投影区域体积。使用Kruskal-Wallis检验评估组间差异，使用Pearson相关性与Yeo-Johnson转换检验PET-MRI相关性，以减少异常值影响。结果HC、AD/aMCI和PD组的[11C]MRB、PET、SUVr-BP或MRI测量结果无显著组间差异。LC [11C]MRB PET SUVr-BP与LC MRI-CNR相关（r = 0.429, 95% CI [0.082 ~ 0.684], p = 0.018）。相比之下，PET-MRI在投射区的相关性较弱且不显著。探索性分析证实了认知、神经精神症状和功能测量方面的预期差异，在AD/aMCI参与者中最为明显。这项概念验证研究表明，使用[11C]MRB PET和LC MRI-CNR对LC完整性进行了趋同的多模态评估，而投影区域显示出不同或缺失的关联。这些发现突出了LC作为多模式生物标志物开发目标的潜力，并支持在更大的纵向队列中进一步研究这些成像策略，以描述它们在检测神经退行性变中去甲肾上腺素能易感性方面的作用。本研究结合[11C]MRB PET和MRI检查阿尔茨海默病和帕金森病的去甲肾上腺素能完整性。结果显示，在蓝斑区有很强的PET-MRI收敛，但在投射区没有，突出了蓝斑是一个敏感的生物标志物靶点，并支持多模态成像方法早期检测神经退行性易感性。
{"title":"Integrating [11C]methylreboxetine PET and MRI to map in vivo norepinephrine transporter distribution: A proof-of-concept study of noradrenergic vulnerability in neurodegeneration","authors":"Jaime D. Mondragon , Sofia Marcolini , Bruno Lima Giacobbo , Philip H. Elsinga , Rudi A.J.O. Dierckx , Marleen Tollenaere , Debby van Dam , Peter P. De Deyn","doi":"10.1016/j.nucmedbio.2025.109581","DOIUrl":"10.1016/j.nucmedbio.2025.109581","url":null,"abstract":"<div><h3>Background</h3><div>The locus coeruleus (LC) and its noradrenergic projections are among the earliest sites displaying pathology in Alzheimer's disease (AD) and Parkinson's disease (PD). In vivo measures of norepinephrine transporter (NET) availability with [<sup>11</sup>C]methylreboxetine ([<sup>11</sup>C]MRB) positron emission tomography (PET) and structural magnetic resonance imaging (MRI) indices of LC integrity provide complementary, but rarely integrated biomarkers.</div></div><div><h3>Methods</h3><div>13 Healthy controls (HC), individuals with 12 AD or amnestic mild cognitive impairment due to AD (AD/aMCI), and 5 patients with PD underwent [<sup>11</sup>C]MRB PET and high-resolution T1-weighted MRI. NET availability was quantified using [<sup>11</sup>C]MRB PET SUV-ratio–based binding potential (SUVr-BP) in the LC and projection regions (hippocampus, amygdala, thalamus, and prefrontal cortex). LC structural integrity was indexed by LC MRI contrast-to-noise ratio (CNR), and projection region volumes were extracted with FreeSurfer. Group differences were assessed with Kruskal–Wallis tests, and PET–MRI associations were examined using Pearson correlations with Yeo–Johnson transformation to reduce outlier influence.</div></div><div><h3>Results</h3><div>No significant group-level differences in [<sup>11</sup>C]MRB PET SUVr-BP or MRI measures were observed across HC, AD/aMCI, and PD. However, LC [<sup>11</sup>C]MRB PET SUVr-BP correlated with LC MRI-CNR (<em>r</em> = 0.429, 95 % CI [0.082–0.684], <em>p</em> = 0.018). In contrast, PET–MRI associations in projection regions were weak and non-significant. Exploratory analyses confirmed expected differences in cognition, neuropsychiatric symptoms, and functional measures, most pronounced in AD/aMCI participants.</div></div><div><h3>Conclusions</h3><div>This proof-of-concept study demonstrates convergent multimodal assessment of LC integrity using [<sup>11</sup>C]MRB PET and LC MRI-CNR, whereas projection regions showed divergent or absent associations. These findings highlight the potential of the LC as a target for multimodal biomarker development and support further investigation of these imaging strategies in larger, longitudinal cohorts to delineate their role in detecting noradrenergic vulnerability in neurodegeneration.</div></div><div><h3>Significance statement</h3><div>This study integrates [<sup>11</sup>C]MRB PET and MRI to examine noradrenergic integrity in Alzheimer's and Parkinson's disease. Results demonstrate strong PET–MRI convergence in the locus coeruleus, but not in projection regions, highlighting the locus coeruleus as a sensitive biomarker target and supporting multimodal imaging approaches for early detection of neurodegenerative vulnerability.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109581"},"PeriodicalIF":3.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-16DOI: 10.1016/j.nucmedbio.2025.109582
Ian M. Horn , Anna C. Bitzer , Patrick L. Day , Mark S. Jacobson , Jeffrey M. McEarchern
Background
Gallium-68 (68Ga) is a PET isotope that is finding more use in the clinical setting as a PET diagnostic tool, e.g. 68Ga PSMA is widely used in the diagnosis of prostate cancer, and 68Ga dotatate for the diagnosis of neuroendocrine tumors. Current production is mostly performed using either germanium-68/gallium-68 (68Ge/68Ga) generators or liquid targets containing zinc-68 (68Zn) and irradiated with protons in an accelerator. Recently, GE Healthcare published an article describing the production and purification of 68Ga using solid 68Zn target irradiation. The method described in this study to recover 68Zn from liquid target effluent may also be used to re-purify 68Zn from effluents from 68Ga production using solid targets. Preliminary studies, to be published in a follow-up paper, that result in electroplated solid 68Zn targets are briefly mentioned to demonstrate that such targets can be made from the 68Zn purified using this recovery method.
Method
An ion-exchange based method was used for purifying (or ‘recovering’) target material-containing effluent for future reuse in target preparation. This was accomplished using a column with Bio-Rad AG1-X8 resin bed of approximately 20–25 g of resin in a glass ion-exchange column. Eluted fractions from the ion-exchange column were tested using a NexION 350D ICP-MS to detect the presence of total zinc and trace contaminants Cu, Fe, Pb, Cr, Al, Mn, Ti, Ni, and Ag. The isotopic purity of the 68Zn in the effluent was also measured to confirm the original isotopic ratio.
Results
The results presented indicate that any contaminants in the effluent samples were reduced to levels below the limits of detection of analytical techniques commonly used in PET manufacturing laboratories (including ICP-OES).
Conclusion
This article provides a simple method for recovering 68Zn from liquid target effluent to be used in the plating of 68Zn targets for 68Ga solid target production. This method will allow academic/PET facilities to establish a wet chemistry process for recovering 68Zn and, using separation schemes published or developed elsewhere, and other precursors used for making solid cyclotron targets for isotope production.
{"title":"Recovery of zinc-68 from gallium-68 cyclotron target effluent: A method to establish wet chemistry capabilities for metal precursor recovery in PET radiometals","authors":"Ian M. Horn , Anna C. Bitzer , Patrick L. Day , Mark S. Jacobson , Jeffrey M. McEarchern","doi":"10.1016/j.nucmedbio.2025.109582","DOIUrl":"10.1016/j.nucmedbio.2025.109582","url":null,"abstract":"<div><h3>Background</h3><div>Gallium-68 (68Ga) is a PET isotope that is finding more use in the clinical setting as a PET diagnostic tool, e.g. 68Ga PSMA is widely used in the diagnosis of prostate cancer, and 68Ga dotatate for the diagnosis of neuroendocrine tumors. Current production is mostly performed using either germanium-68/gallium-68 (68Ge/68Ga) generators or liquid targets containing zinc-68 (68Zn) and irradiated with protons in an accelerator. Recently, GE Healthcare published an article describing the production and purification of 68Ga using solid 68Zn target irradiation. The method described in this study to recover 68Zn from liquid target effluent may also be used to re-purify 68Zn from effluents from 68Ga production using solid targets. Preliminary studies, to be published in a follow-up paper, that result in electroplated solid 68Zn targets are briefly mentioned to demonstrate that such targets can be made from the 68Zn purified using this recovery method.</div></div><div><h3>Method</h3><div>An ion-exchange based method was used for purifying (or ‘recovering’) target material-containing effluent for future reuse in target preparation. This was accomplished using a column with Bio-Rad AG1-X8 resin bed of approximately 20–25 g of resin in a glass ion-exchange column. Eluted fractions from the ion-exchange column were tested using a NexION 350D ICP-MS to detect the presence of total zinc and trace contaminants Cu, Fe, Pb, Cr, Al, Mn, Ti, Ni, and Ag. The isotopic purity of the 68Zn in the effluent was also measured to confirm the original isotopic ratio.</div></div><div><h3>Results</h3><div>The results presented indicate that any contaminants in the effluent samples were reduced to levels below the limits of detection of analytical techniques commonly used in PET manufacturing laboratories (including ICP-OES).</div></div><div><h3>Conclusion</h3><div>This article provides a simple method for recovering 68Zn from liquid target effluent to be used in the plating of 68Zn targets for 68Ga solid target production. This method will allow academic/PET facilities to establish a wet chemistry process for recovering 68Zn and, using separation schemes published or developed elsewhere, and other precursors used for making solid cyclotron targets for isotope production.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"152 ","pages":"Article 109582"},"PeriodicalIF":3.0,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.nucmedbio.2025.109118
Frederik Sachse, Markus Laube, Klaus Kopka, Sven Stadlbauer, Austin Craig
{"title":"Exploring Ethyl- and Propylpinacol-Based Arylboronic Acid Esters as Stable Precursors for Copper-Mediated Radiohalogenation","authors":"Frederik Sachse, Markus Laube, Klaus Kopka, Sven Stadlbauer, Austin Craig","doi":"10.1016/j.nucmedbio.2025.109118","DOIUrl":"10.1016/j.nucmedbio.2025.109118","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"150 ","pages":"Article 109118"},"PeriodicalIF":3.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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