Current methods for diagnosing primary aldosteronism (PA) are limited by their invasiveness and diagnostic accuracy. This study aimed to develop nuclear medicine imaging tracers targeting CYP11B2, which is overexpressed in patients with PA.
Results
We successfully synthesized iodinated and fluoroethoxynated pyridinyldihydroquinolinone (PDHQ) derivatives, among which PDHQ-1 exhibited the highest selectivity for CYP11B2. Furthermore, [125I]PDHQ-1 accumulated in the adrenal gland soon after administration, reaching its highest saturation compared to that in other organs 5 min after administration; however, its radioactivity decreased over time. Autoradiographic analysis revealed that [125I]PDHQ-1 displayed a 4.4-fold higher accumulation in the CYP11B2 region of adrenal sections from human patients with aldosterone-producing adenomas than in the CYP11B1 region. In contrast, [125I]IMTO, which is a highly specific radiotracer for imaging adrenocortical tissue, displayed similar accumulation in the CYP11B2 and CYP11B1 regions.
Conclusions
Collectively, our results suggest that [125I]PDHQ-1, featuring a pyridinyldihydroquinolinone scaffold, shows potential as an imaging tracer for PA.
{"title":"Development of a CYP11B2 imaging tracer for primary aldosteronism: basic evaluation of iodine- and fluorine-incorporated pyridinyldihydroquinolinone derivatives","authors":"Yusuke Yagi, Hiroyuki Kimura, Riko Fuseda, Takaaki Murakami, Marina Omokawa, Kaito Ohta, Satoko Kise, Masakatsu Sone, Hiroyuki Yasui, Nobuya Inagaki, Hideo Saji","doi":"10.1186/s41181-025-00361-8","DOIUrl":"10.1186/s41181-025-00361-8","url":null,"abstract":"<div><h3>Background</h3><p>Current methods for diagnosing primary aldosteronism (PA) are limited by their invasiveness and diagnostic accuracy. This study aimed to develop nuclear medicine imaging tracers targeting CYP11B2, which is overexpressed in patients with PA.</p><h3>Results</h3><p>We successfully synthesized iodinated and fluoroethoxynated pyridinyldihydroquinolinone (PDHQ) derivatives, among which PDHQ-1 exhibited the highest selectivity for CYP11B2. Furthermore, [<sup>125</sup>I]PDHQ-1 accumulated in the adrenal gland soon after administration, reaching its highest saturation compared to that in other organs 5 min after administration; however, its radioactivity decreased over time. Autoradiographic analysis revealed that [<sup>125</sup>I]PDHQ-1 displayed a 4.4-fold higher accumulation in the CYP11B2 region of adrenal sections from human patients with aldosterone-producing adenomas than in the CYP11B1 region. In contrast, [<sup>125</sup>I]IMTO, which is a highly specific radiotracer for imaging adrenocortical tissue, displayed similar accumulation in the CYP11B2 and CYP11B1 regions.</p><h3>Conclusions</h3><p>Collectively, our results suggest that [<sup>125</sup>I]PDHQ-1, featuring a pyridinyldihydroquinolinone scaffold, shows potential as an imaging tracer for PA.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-03DOI: 10.1186/s41181-025-00360-9
Simran Deep Kaur, Deepak N. Kapoor
{"title":"Cancer in translation: cyanine carborane salts: a multifunctional theranostic approach to cancer treatment","authors":"Simran Deep Kaur, Deepak N. Kapoor","doi":"10.1186/s41181-025-00360-9","DOIUrl":"10.1186/s41181-025-00360-9","url":null,"abstract":"","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as a promising class of therapeutics, particularly in the treatment of cancers with defective DNA repair mechanisms, such as those with breast cancer genes (BRCA) mutations. Their effectiveness in cancer therapy is now well-established, but the ongoing advancements in radiochemistry are expanding their potential to combine both therapeutic and imaging capabilities. Radiolabelled PARP inhibitors, used in conjunction with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), might enable precise imaging of PARP expression in tumours, potentially providing invaluable insights into treatment response, tumor heterogeneity, and molecular profiling.
Main body
The radiochemistry of PARP inhibitors involves incorporating radioisotopes (most of all Fluorine-18) into the molecular structure of these molecules. The first strategy used to achieve this goal was the use of prosthetic groups bearing the fluorine-18. Then, the development of radioisotopologue have gained ground, followed later by the replacement with other halogens such as bromine, iodine, or astatine has taken place. Another frontier is represented by the metal radiolabelling of these inhibitors through the introduction of a chelator moiety to these molecules, thus further expanding both imaging and therapy applications.
Conclusion
Finally, emerging evidence suggest the possibility to involve PARP-related radiopharmaceuticals in theranostics approaches. Despite challenges such as the complexity of radiolabelling, regulatory hurdles, and the need for more robust clinical validation, the continued exploration of the radiochemistry of PARP inhibitors promises to revolutionize both the diagnosis and treatment of cancer, offering hope for more effective and personalized cancer care.
{"title":"Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging","authors":"Gianluca Destro, Rebecca Rizzo, Chiara Rua, Raha Rouhbakhsh Azimi, Silvia Morbelli","doi":"10.1186/s41181-025-00364-5","DOIUrl":"10.1186/s41181-025-00364-5","url":null,"abstract":"<div><h3>Background</h3><p>Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as a promising class of therapeutics, particularly in the treatment of cancers with defective DNA repair mechanisms, such as those with breast cancer genes (BRCA) mutations. Their effectiveness in cancer therapy is now well-established, but the ongoing advancements in radiochemistry are expanding their potential to combine both therapeutic and imaging capabilities. Radiolabelled PARP inhibitors, used in conjunction with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), might enable precise imaging of PARP expression in tumours, potentially providing invaluable insights into treatment response, tumor heterogeneity, and molecular profiling.</p><h3>Main body</h3><p>The radiochemistry of PARP inhibitors involves incorporating radioisotopes (most of all Fluorine-18) into the molecular structure of these molecules. The first strategy used to achieve this goal was the use of prosthetic groups bearing the fluorine-18. Then, the development of radioisotopologue have gained ground, followed later by the replacement with other halogens such as bromine, iodine, or astatine has taken place. Another frontier is represented by the metal radiolabelling of these inhibitors through the introduction of a chelator moiety to these molecules, thus further expanding both imaging and therapy applications.</p><h3>Conclusion</h3><p>Finally, emerging evidence suggest the possibility to involve PARP-related radiopharmaceuticals in theranostics approaches. Despite challenges such as the complexity of radiolabelling, regulatory hurdles, and the need for more robust clinical validation, the continued exploration of the radiochemistry of PARP inhibitors promises to revolutionize both the diagnosis and treatment of cancer, offering hope for more effective and personalized cancer care.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1186/s41181-025-00363-6
Rosalba Mansi, Natalie Bertarelli, Luigi Del Pozzo, Sandra Zanger, Tais Basaco Bernabeu, Helmut Maecke, Melpomeni Fani
<div><h3>Background</h3><p>The radiolabeled somatostatin receptor subtype 2 (SST<sub>2</sub>) antagonists LM3 (Phe(4-Cl)<sup>1</sup>‐c(<span>d</span>Cys<sup>2</sup>‐Tyr<sup>3</sup>‐<span>d</span>Aph(Cbm)<sup>4</sup>‐Lys<sup>5</sup>‐Thr<sup>6</sup>‐Cys<sup>7</sup>)-<span>d</span>Tyr<sup>8</sup>-NH<sub>2</sub>) and JR11 (Phe(4-Cl)<sup>1</sup>‐c(<span>d</span>Cys<sup>2</sup>‐Aph(Hor)<sup>3</sup>‐<span>d</span>Aph(Cbm)<sup>4</sup>‐Lys<sup>5</sup>‐Thr<sup>6</sup>‐Cys<sup>7</sup>)-<span>d</span>Tyr<sup>8</sup>-NH<sub>2</sub>) are under clinical evaluation for imaging and treatment of neuroendocrine tumors. These peptides differ at position 3, where LM3 contains Tyr<sup>3</sup>, while JR11 incorporates Aph(Hor)<sup>3</sup>. The amino acid at this position is crucial in the design of somatostatin ligands, agonists and antagonists, influencing affinity and receptor subtype specificity. Pyridylalanine, a nonnatural amino acid, presents three regioisomers 2-pyridylalanine (2Pal), 3-pyridylalanine (3Pal), and 4-pyridylalanine (4Pal), which differ only in the nitrogen atom’s position in the aromatic ring, allowing minimal chemical modification. We investigated whether the new somatostatin antagonists DOTA-[2Pal<sup>3</sup>]-LM3, DOTA-[3Pal<sup>3</sup>]-LM3 and DOTA-[4Pal<sup>3</sup>]-LM3, radiolabeled with Lu-177, differ among them and how they compare with the clinically used [<sup>177</sup>Lu]Lu-DOTA-LM3.</p><h3>Results</h3><p>The synthesis of the DOTA-[2Pal<sup>3</sup>]-LM3 resulted in the formation of two diastereomers, with the <span>d</span>2Pal derivative lacking receptor recognition and affinity, contrary to the enantiomer <span>l (l</span>2Pal) derivative. The hydrophilicity of [<sup>177</sup>Lu]Lu-DOTA-[xPal<sup>3</sup>]-LM3 increased in the order of <span>l</span>2Pal < 3Pal < 4Pal (log<i>D</i> = -2.3 ± 0.1 -2.5 ± 0.1 and -2.6 ± 0.1, respectively), being similar or significantly higher than [<sup>177</sup>Lu]Lu-DOTA-LM3 (log<i>D</i> = -2.3 ± 0.1). Saturation binding studies indicated a trend of affinity improvement by <span>l</span>2Pal < 3Pal < 4Pal (K<sub>D</sub> = 0.18 ± 0.02, 0.15 ± 0.01 and 0.11 ± 0.01 nM, respectively), which is similar to [<sup>177</sup>Lu]Lu-DOTA-LM3 (K<sub>D</sub> = 0.09 ± 0.02 nM). Surprisingly, despite similar accumulation in SST<sub>2</sub>-positive tumors, differences were observed in the body distribution. The hydrophilicity of the Pal amino acids is likely responsible for the higher kidney uptake of the three <sup>177</sup>Lu-Pal-radioligands when compared to [<sup>177</sup>Lu]Lu-DOTA-LM3. In particular, [<sup>177</sup>Lu]Lu-DOTA-[3Pal<sup>3</sup>]-LM3 is characterized by high uptake and long retention in kidneys, probably due to its high stability in renal tissue. Chromatographic analysis of kidney homogenates revealed that more than 60% of peptide remained intact 1 h after injection.</p><h3>Conclusions</h3><p>Our study revealed that the replacement of Tyr<sup>3</sup> with Pal<sup>3</sup> isomers does no
{"title":"Pyridyl-Ala in the third position of radiolabeled somatostatin antagonists: the effect of regioisomeric substitution","authors":"Rosalba Mansi, Natalie Bertarelli, Luigi Del Pozzo, Sandra Zanger, Tais Basaco Bernabeu, Helmut Maecke, Melpomeni Fani","doi":"10.1186/s41181-025-00363-6","DOIUrl":"10.1186/s41181-025-00363-6","url":null,"abstract":"<div><h3>Background</h3><p>The radiolabeled somatostatin receptor subtype 2 (SST<sub>2</sub>) antagonists LM3 (Phe(4-Cl)<sup>1</sup>‐c(<span>d</span>Cys<sup>2</sup>‐Tyr<sup>3</sup>‐<span>d</span>Aph(Cbm)<sup>4</sup>‐Lys<sup>5</sup>‐Thr<sup>6</sup>‐Cys<sup>7</sup>)-<span>d</span>Tyr<sup>8</sup>-NH<sub>2</sub>) and JR11 (Phe(4-Cl)<sup>1</sup>‐c(<span>d</span>Cys<sup>2</sup>‐Aph(Hor)<sup>3</sup>‐<span>d</span>Aph(Cbm)<sup>4</sup>‐Lys<sup>5</sup>‐Thr<sup>6</sup>‐Cys<sup>7</sup>)-<span>d</span>Tyr<sup>8</sup>-NH<sub>2</sub>) are under clinical evaluation for imaging and treatment of neuroendocrine tumors. These peptides differ at position 3, where LM3 contains Tyr<sup>3</sup>, while JR11 incorporates Aph(Hor)<sup>3</sup>. The amino acid at this position is crucial in the design of somatostatin ligands, agonists and antagonists, influencing affinity and receptor subtype specificity. Pyridylalanine, a nonnatural amino acid, presents three regioisomers 2-pyridylalanine (2Pal), 3-pyridylalanine (3Pal), and 4-pyridylalanine (4Pal), which differ only in the nitrogen atom’s position in the aromatic ring, allowing minimal chemical modification. We investigated whether the new somatostatin antagonists DOTA-[2Pal<sup>3</sup>]-LM3, DOTA-[3Pal<sup>3</sup>]-LM3 and DOTA-[4Pal<sup>3</sup>]-LM3, radiolabeled with Lu-177, differ among them and how they compare with the clinically used [<sup>177</sup>Lu]Lu-DOTA-LM3.</p><h3>Results</h3><p>The synthesis of the DOTA-[2Pal<sup>3</sup>]-LM3 resulted in the formation of two diastereomers, with the <span>d</span>2Pal derivative lacking receptor recognition and affinity, contrary to the enantiomer <span>l (l</span>2Pal) derivative. The hydrophilicity of [<sup>177</sup>Lu]Lu-DOTA-[xPal<sup>3</sup>]-LM3 increased in the order of <span>l</span>2Pal < 3Pal < 4Pal (log<i>D</i> = -2.3 ± 0.1 -2.5 ± 0.1 and -2.6 ± 0.1, respectively), being similar or significantly higher than [<sup>177</sup>Lu]Lu-DOTA-LM3 (log<i>D</i> = -2.3 ± 0.1). Saturation binding studies indicated a trend of affinity improvement by <span>l</span>2Pal < 3Pal < 4Pal (K<sub>D</sub> = 0.18 ± 0.02, 0.15 ± 0.01 and 0.11 ± 0.01 nM, respectively), which is similar to [<sup>177</sup>Lu]Lu-DOTA-LM3 (K<sub>D</sub> = 0.09 ± 0.02 nM). Surprisingly, despite similar accumulation in SST<sub>2</sub>-positive tumors, differences were observed in the body distribution. The hydrophilicity of the Pal amino acids is likely responsible for the higher kidney uptake of the three <sup>177</sup>Lu-Pal-radioligands when compared to [<sup>177</sup>Lu]Lu-DOTA-LM3. In particular, [<sup>177</sup>Lu]Lu-DOTA-[3Pal<sup>3</sup>]-LM3 is characterized by high uptake and long retention in kidneys, probably due to its high stability in renal tissue. Chromatographic analysis of kidney homogenates revealed that more than 60% of peptide remained intact 1 h after injection.</p><h3>Conclusions</h3><p>Our study revealed that the replacement of Tyr<sup>3</sup> with Pal<sup>3</sup> isomers does no","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1186/s41181-025-00362-7
Jarred Michael Scaffidi-Muta, Andrew David Abell
Background
The selective delivery of α-emitting radionuclides is emerging as a highly effective form of cancer therapy. With a short range and high cytotoxicity, α-particles can selectively kill cancerous cells whilst minimising harm to surrounding healthy tissue. As the parent of the α-emitter 212Bi, 212Pb has seen increasing therapeutic use on account of its favourable chemistry, half-life, and decay properties. This review comprehensively discusses the clinical development of 212Pb in recent years, particularly its production, chelation chemistry, and therapeutic adoption.
Main body
Improvements in generator technology and supply have overcome the historically limited availability of 212Pb, enabling a surge of research in the field. Numerous bifunctional chelators have since been developed, which enable facile conjugation of 212Pb to a plethora of tumour targeting carriers. Advancements in nuclear imaging techniques, and the use 203Pb as an imaging surrogate, have enabled accurate biodistribution and dosimetry information to inform preclinical studies. These factors have attracted considerable commercial interest in 212Pb, culminating in the rapid translation of this radionuclide into the clinic, where it is being investigated in the treatment of a range of malignancies.
Conclusion
Radiotherapy with 212Pb has shown enormous promise in preclinical and clinical studies. While challenges still remain before 212Pb can be more widely adopted, remarkable progress has been made in addressing these. At present, the therapeutic potential of 212Pb is only beginning to be realised.
{"title":"212Pb in targeted radionuclide therapy: a review","authors":"Jarred Michael Scaffidi-Muta, Andrew David Abell","doi":"10.1186/s41181-025-00362-7","DOIUrl":"10.1186/s41181-025-00362-7","url":null,"abstract":"<div><h3>Background</h3><p>The selective delivery of α-emitting radionuclides is emerging as a highly effective form of cancer therapy. With a short range and high cytotoxicity, α-particles can selectively kill cancerous cells whilst minimising harm to surrounding healthy tissue. As the parent of the α-emitter <sup>212</sup>Bi, <sup>212</sup>Pb has seen increasing therapeutic use on account of its favourable chemistry, half-life, and decay properties. This review comprehensively discusses the clinical development of <sup>212</sup>Pb in recent years, particularly its production, chelation chemistry, and therapeutic adoption.</p><h3>Main body</h3><p>Improvements in generator technology and supply have overcome the historically limited availability of <sup>212</sup>Pb, enabling a surge of research in the field. Numerous bifunctional chelators have since been developed, which enable facile conjugation of <sup>212</sup>Pb to a plethora of tumour targeting carriers. Advancements in nuclear imaging techniques, and the use <sup>203</sup>Pb as an imaging surrogate, have enabled accurate biodistribution and dosimetry information to inform preclinical studies. These factors have attracted considerable commercial interest in <sup>212</sup>Pb, culminating in the rapid translation of this radionuclide into the clinic, where it is being investigated in the treatment of a range of malignancies.</p><h3>Conclusion</h3><p>Radiotherapy with <sup>212</sup>Pb has shown enormous promise in preclinical and clinical studies. While challenges still remain before <sup>212</sup>Pb can be more widely adopted, remarkable progress has been made in addressing these. At present, the therapeutic potential of <sup>212</sup>Pb is only beginning to be realised.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-01DOI: 10.1186/s41181-025-00359-2
Fabian Krutzek, Cornelius K. Donat, Sven Stadlbauer
Background
Immune checkpoint inhibitor therapy addressing the PD-1/PD-L1 axis is a promising approach in cancer treatment. A clinically suitable radiotracer would allow molecular imaging of the temporospatial changes in tumor PD-L1 expression. This could enable the clinicians to select eligible patients for checkpoint therapy and monitor therapeutic efficacy.
Results
Four biphenyl-based small-molecule PD-L1 ligands were synthesized using a convergent synthetic route, with a linear sequence of up to eleven steps. Two candidates were covalently labeled with 18F via either an azido glycosyl or PEG2 moiety, while the other two were modified with a RESCA chelator for Al[18F]F2+-labeling. The lipophilicity was assessed through determination of log D7.4 values. In vitro binding affinities (inhibition constant, Ki) toward PD-L1 were determined in competition with one of our previously published biphenyl-based small-molecule (KD = ~ 21 nM). Compared to this compound, both covalently labeled 18F-ligands exhibited decreased water solubility (log D7.4 ~ − 2.5 and − 2.7), along with a markedly reduced (Ki = 200‒500 nM) affinity. This was in line with in vivo small animal PET, where both compounds were characterized by a negligible tumor uptake, lack of contrast between target-positive/negative tumors and exclusively unfavorable hepatobiliary excretion. Similar results were observed for the chelator-modified ligands with slightly increased hydrophilicity (log D7.4 ~ − 2.8 and − 2.9), showing a binding affinity of 150 nM for one compound, while binding was lost completely for the other. Again, a poor in vivo performance was observed, characterized by hepatobiliary clearance and lack of specific tumor uptake in the PD-L1 positive tumor.
Conclusion
Four biphenyl-based, 18F-labeled PD-L1 radioligands were developed using prosthetic groups (azido glycosyl or PEG2) for covalent fluorination and Al[18F]F2⁺-complexation with the RESCA chelator. Despite limited in vitro and in vivo performance, these fluorination approaches offer a foundation for developing improved PD-L1 radioligands after increasing the hydrophilicity and the spacing between the radiolabel and binding motif.
{"title":"Structure–activity relationship of 18F-labeled PD-L1-targeting small molecule ligands: impact of radiolabeling strategy on affinity and in vivo performance","authors":"Fabian Krutzek, Cornelius K. Donat, Sven Stadlbauer","doi":"10.1186/s41181-025-00359-2","DOIUrl":"10.1186/s41181-025-00359-2","url":null,"abstract":"<div><h3>Background</h3><p>Immune checkpoint inhibitor therapy addressing the PD-1/PD-L1 axis is a promising approach in cancer treatment. A clinically suitable radiotracer would allow molecular imaging of the temporospatial changes in tumor PD-L1 expression. This could enable the clinicians to select eligible patients for checkpoint therapy and monitor therapeutic efficacy.</p><h3>Results</h3><p>Four biphenyl-based small-molecule PD-L1 ligands were synthesized using a convergent synthetic route, with a linear sequence of up to eleven steps. Two candidates were covalently labeled with <sup>18</sup>F via either an azido glycosyl or PEG2 moiety, while the other two were modified with a RESCA chelator for Al[<sup>18</sup>F]F<sup>2+</sup>-labeling. The lipophilicity was assessed through determination of log <i>D</i><sub>7.4</sub> values. In vitro binding affinities (inhibition constant, <i>K</i><sub>i</sub>) toward PD-L1 were determined in competition with one of our previously published biphenyl-based small-molecule (<i>K</i><sub>D</sub> = ~ 21 nM). Compared to this compound, both covalently labeled <sup>18</sup>F-ligands exhibited decreased water solubility (log <i>D</i><sub>7.4</sub> ~ − 2.5 and − 2.7), along with a markedly reduced (<i>K</i><sub>i</sub> = 200‒500 nM) affinity. This was in line with in vivo small animal PET, where both compounds were characterized by a negligible tumor uptake, lack of contrast between target-positive/negative tumors and exclusively unfavorable hepatobiliary excretion. Similar results were observed for the chelator-modified ligands with slightly increased hydrophilicity (log <i>D</i><sub>7.4</sub> ~ − 2.8 and − 2.9), showing a binding affinity of 150 nM for one compound, while binding was lost completely for the other. Again, a poor in vivo performance was observed, characterized by hepatobiliary clearance and lack of specific tumor uptake in the PD-L1 positive tumor.</p><h3>Conclusion</h3><p>Four biphenyl-based, <sup>18</sup>F-labeled PD-L1 radioligands were developed using prosthetic groups (azido glycosyl or PEG2) for covalent fluorination and Al[<sup>18</sup>F]F<sup>2</sup>⁺-complexation with the RESCA chelator. Despite limited in vitro and in vivo performance, these fluorination approaches offer a foundation for developing improved PD-L1 radioligands after increasing the hydrophilicity and the spacing between the radiolabel and binding motif.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-21DOI: 10.1186/s41181-025-00356-5
Abdelrahman Homedan, Darpan N. Pandya, Nicholas J. Schnicker, Thaddeus J. Wadas
Background
Fibroblast activation protein alpha (FAP) is a serine protease that is expressed at basal levels in benign tissues but is overexpressed in a variety of pathologies, including cancer. Consequently, significant research efforts have been expended to develop diagnostic radiopharmaceuticals and effective radiotherapies that target this protein. The aim of this review is to summarize the current progress on the development of protein-based radiopharmaceuticals that target FAP.
Main body
A literature survey spanning nearly 40 years was conducted to assess the historical development and current progress in protein-based radiopharmaceuticals that target FAP. To date, more than 20 publications have been introduced that describe these agents in preclinical and clinical settings. This review summarizes the development and evaluation of radiopharmaceuticals involving antibodies, antibody fragments, and single domain antibodies.
Conclusion
The results of this literature review demonstrate that while significant research efforts have been expended on peptide-based radiopharmaceuticals and small molecule FAP inhibitors, the development of protein-based radiopharmaceuticals that target FAP remains an active research area that has yet to reach its full potential.
{"title":"Protein-based Radiopharmaceuticals that target fibroblast activation protein alpha: a review of current progress","authors":"Abdelrahman Homedan, Darpan N. Pandya, Nicholas J. Schnicker, Thaddeus J. Wadas","doi":"10.1186/s41181-025-00356-5","DOIUrl":"10.1186/s41181-025-00356-5","url":null,"abstract":"<div><h3>Background</h3><p>Fibroblast activation protein alpha (FAP) is a serine protease that is expressed at basal levels in benign tissues but is overexpressed in a variety of pathologies, including cancer. Consequently, significant research efforts have been expended to develop diagnostic radiopharmaceuticals and effective radiotherapies that target this protein. The aim of this review is to summarize the current progress on the development of protein-based radiopharmaceuticals that target FAP.</p><h3>Main body</h3><p>A literature survey spanning nearly 40 years was conducted to assess the historical development and current progress in protein-based radiopharmaceuticals that target FAP. To date, more than 20 publications have been introduced that describe these agents in preclinical and clinical settings. This review summarizes the development and evaluation of radiopharmaceuticals involving antibodies, antibody fragments, and single domain antibodies.</p><h3>Conclusion</h3><p>The results of this literature review demonstrate that while significant research efforts have been expended on peptide-based radiopharmaceuticals and small molecule FAP inhibitors, the development of protein-based radiopharmaceuticals that target FAP remains an active research area that has yet to reach its full potential. </p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1186/s41181-025-00354-7
Johanna Trommer, Martin Ullrich, Falco Reissig, Santiago Andres Brühlmann, Anne-Kathrin Nitt-Weber, Zbynek Novy, Katarina Hajduova, Daniela Kurfurstova, Romana Hendrychova, Jan Bouchal, Milos Petrik, Christin Neuber, Wiebke Sihver, Sven Stadlbauer, Jens Pietzsch, Martin Kreller, Klaus Kopka, Constantin Mamat, Kristof Zarschler
<div> <span>AbstractSection</span> Background <p>Targeted alpha therapy represents an advanced and rapidly evolving form of precision cancer treatment with increasing importance in recent years. The alpha-emitter <sup>225</sup>Ac plays a key role in this clinical development due to its attractive physical and chemical properties. In this context, the macropa chelator has favorable characteristics in terms of labeling conditions and complex stability, making its derivatives exceptionally appealing for <sup>225</sup>Ac-labeling of heat-sensitive biomolecules. However, preclinical evaluation of such <sup>225</sup>Ac-containing molecules and comprehensive assessment of their pharmacokinetics, dosimetry and radiobiology necessitate a suitable diagnostic counterpart. Due to its attractive radiation properties, <sup>133</sup>La represents an adequate positron-emitting radionuclide to form a matched pair with <sup>225</sup>Ac for macropa-based radiopharmaceuticals. Herein, we describe the preparation and radiopharmacological characterization of macropa-functionalized, <sup>133</sup>La/<sup>225</sup>Ac-labeled single-domain antibodies (sdAbs) targeting the epidermal growth factor receptor (EGFR) to demonstrate the general suitability of this theranostic pair of radionuclides.</p> <span>AbstractSection</span> Results <p>The synthesis of a clickable, bicyclononyne-modified macropa chelator and its site-specific conjugation to azide-modified, monovalent and biparatopic sdAbs is presented. Subsequent labeling at room temperature (rt) for 15 min resulted in molar activities of 30 MBq/nmol for <sup>133</sup>La and 0.5 MBq/nmol for <sup>225</sup>Ac, respectively. In vitro studies using the <sup>133</sup>La-labeled sdAbs revealed comparable binding characteristics, but an enhanced cellular internalization of the biparatopic variant compared to its monovalent counterparts. This increased uptake consequently resulted in higher cytotoxicity of the <sup>225</sup>Ac-labeled biparatopic conjugate. In vivo PET imaging of the <sup>133</sup>La-labeled conjugates indicated comparable uptake and retention of the mono- and biparatopic variants in liver and kidneys, with the former showing slightly higher tumor accumulation. Ex vivo biodistribution studies conducted with <sup>225</sup>Ac-labeled conjugates largely confirmed the findings obtained by PET imaging, albeit with a marginally higher tumor accumulation of the biparatopic <sup>225</sup>Ac-radioimmunoconjugate. Final histological examinations of tumor and kidney tissues showed DNA damage in the renal cortex of the <sup>225</sup>Ac-radioimmunoconjugate-treated mice, but no differences in the number of γ-H2AX-positive cells in the corresponding tumor tissues could be detected.</p> <span>AbstractSection</span> Conclusions <p>We present a comp
{"title":"It’s a match: use of the radionuclide theranostic pair 133La/225Ac for the radiopharmacological characterization of EGFR-targeted single-domain antibodies","authors":"Johanna Trommer, Martin Ullrich, Falco Reissig, Santiago Andres Brühlmann, Anne-Kathrin Nitt-Weber, Zbynek Novy, Katarina Hajduova, Daniela Kurfurstova, Romana Hendrychova, Jan Bouchal, Milos Petrik, Christin Neuber, Wiebke Sihver, Sven Stadlbauer, Jens Pietzsch, Martin Kreller, Klaus Kopka, Constantin Mamat, Kristof Zarschler","doi":"10.1186/s41181-025-00354-7","DOIUrl":"10.1186/s41181-025-00354-7","url":null,"abstract":"<div>\u0000 \u0000 <span>AbstractSection</span>\u0000 Background\u0000 <p>Targeted alpha therapy represents an advanced and rapidly evolving form of precision cancer treatment with increasing importance in recent years. The alpha-emitter <sup>225</sup>Ac plays a key role in this clinical development due to its attractive physical and chemical properties. In this context, the macropa chelator has favorable characteristics in terms of labeling conditions and complex stability, making its derivatives exceptionally appealing for <sup>225</sup>Ac-labeling of heat-sensitive biomolecules. However, preclinical evaluation of such <sup>225</sup>Ac-containing molecules and comprehensive assessment of their pharmacokinetics, dosimetry and radiobiology necessitate a suitable diagnostic counterpart. Due to its attractive radiation properties, <sup>133</sup>La represents an adequate positron-emitting radionuclide to form a matched pair with <sup>225</sup>Ac for macropa-based radiopharmaceuticals. Herein, we describe the preparation and radiopharmacological characterization of macropa-functionalized, <sup>133</sup>La/<sup>225</sup>Ac-labeled single-domain antibodies (sdAbs) targeting the epidermal growth factor receptor (EGFR) to demonstrate the general suitability of this theranostic pair of radionuclides.</p>\u0000 \u0000 <span>AbstractSection</span>\u0000 Results\u0000 <p>The synthesis of a clickable, bicyclononyne-modified macropa chelator and its site-specific conjugation to azide-modified, monovalent and biparatopic sdAbs is presented. Subsequent labeling at room temperature (rt) for 15 min resulted in molar activities of 30 MBq/nmol for <sup>133</sup>La and 0.5 MBq/nmol for <sup>225</sup>Ac, respectively. In vitro studies using the <sup>133</sup>La-labeled sdAbs revealed comparable binding characteristics, but an enhanced cellular internalization of the biparatopic variant compared to its monovalent counterparts. This increased uptake consequently resulted in higher cytotoxicity of the <sup>225</sup>Ac-labeled biparatopic conjugate. In vivo PET imaging of the <sup>133</sup>La-labeled conjugates indicated comparable uptake and retention of the mono- and biparatopic variants in liver and kidneys, with the former showing slightly higher tumor accumulation. Ex vivo biodistribution studies conducted with <sup>225</sup>Ac-labeled conjugates largely confirmed the findings obtained by PET imaging, albeit with a marginally higher tumor accumulation of the biparatopic <sup>225</sup>Ac-radioimmunoconjugate. Final histological examinations of tumor and kidney tissues showed DNA damage in the renal cortex of the <sup>225</sup>Ac-radioimmunoconjugate-treated mice, but no differences in the number of γ-H2AX-positive cells in the corresponding tumor tissues could be detected.</p>\u0000 \u0000 <span>AbstractSection</span>\u0000 Conclusions\u0000 <p>We present a comp","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-13DOI: 10.1186/s41181-025-00350-x
Mario González-Arjona, Lorena Cussó, Luis Alcalá, María Isabel González, Alexandra de Francisco, María Jesús Fernández-Aceñero, Dag Sehlin, Stina Syvänen, Emilio Bouza, Patricia Muñoz, Manuel Desco, Beatriz Salinas
Background
Clostridioides difficile infection (CDI) is a major healthcare challenge that is associated with high morbidity and mortality. Current diagnostic methods are limited in terms of specificity and invasiveness, necessitating novel, non-invasive imaging techniques. In this study, we develop and evaluate an immunoPET radiotracer targeting C. difficile toxin B for in vivo detection of CDI in a murine model.
Results
The monoclonal antibody bezlotoxumab, was radiolabeled with [125I]I for in vitro characterization and with [89Zr]Zr for in vivo PET imaging, resulting in high radiochemical yields (75.36 ± 4.11% for [125I]I and 71.58 ± 8.19% for [89Zr]Zr) and purities (> 99.99% in both cases), with stable binding properties. PET/CT imaging 48 h post-infection in an animal model of CDI (C57BL/6 mice and ribotype 027 strain) demonstrated specific accumulation of [89Zr]Zr-DFO-Beztxab in the colon and cecum of infected mice, thus making it possible to distinguish CDI from dysbiosis without specific C. difficile infection and healthy controls. Findings were confirmed by PET-based quantification and ex vivo biodistribution.
Conclusions
We successfully developed an immunoPET radiotracer targeting toxin B for detection of CDI. Its application in an animal CDI model proved its capacity to detect the source of infection with high specificity, while avoiding confusion with non-specific inflammation.
{"title":"Development of a toxin-selective immunotracer for in vivo detection of Clostridioides difficile infection by immunoPET","authors":"Mario González-Arjona, Lorena Cussó, Luis Alcalá, María Isabel González, Alexandra de Francisco, María Jesús Fernández-Aceñero, Dag Sehlin, Stina Syvänen, Emilio Bouza, Patricia Muñoz, Manuel Desco, Beatriz Salinas","doi":"10.1186/s41181-025-00350-x","DOIUrl":"10.1186/s41181-025-00350-x","url":null,"abstract":"<div><h3>Background</h3><p><i>Clostridioides difficile</i> infection (CDI) is a major healthcare challenge that is associated with high morbidity and mortality. Current diagnostic methods are limited in terms of specificity and invasiveness, necessitating novel, non-invasive imaging techniques. In this study, we develop and evaluate an immunoPET radiotracer targeting <i>C. difficile</i> toxin B for in vivo detection of CDI in a murine model.</p><h3>Results</h3><p>The monoclonal antibody bezlotoxumab, was radiolabeled with [<sup>125</sup>I]I for in vitro characterization and with [<sup>89</sup>Zr]Zr for in vivo PET imaging, resulting in high radiochemical yields (75.36 ± 4.11% for [<sup>125</sup>I]I and 71.58 ± 8.19% for [<sup>89</sup>Zr]Zr) and purities (> 99.99% in both cases), with stable binding properties. PET/CT imaging 48 h post-infection in an animal model of CDI (C57BL/6 mice and ribotype 027 strain) demonstrated specific accumulation of [<sup>89</sup>Zr]Zr-DFO-Beztxab in the colon and cecum of infected mice, thus making it possible to distinguish CDI from dysbiosis without specific <i>C. difficile</i> infection and healthy controls. Findings were confirmed by PET-based quantification and ex vivo biodistribution.</p><h3>Conclusions</h3><p>We successfully developed an immunoPET radiotracer targeting toxin B for detection of CDI. Its application in an animal CDI model proved its capacity to detect the source of infection with high specificity, while avoiding confusion with non-specific inflammation.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-10DOI: 10.1186/s41181-025-00352-9
Olivier Fougère, Anne Dencausse, Nicolas Lepareur, Gaetan Van Simaeys, Gilles Doumont, Isabelle Gardin, Elisabeth Renard, Claire Hollenbeck, Coraline De Maeseneire, Nicolas Passon, Olivier Rousseaux, Sarah Catoen
Background
Despite recent therapeutic advances, managing liver cancer remains a significant medical and economic priority for many countries. Patients often present at an advanced stage, preventing them from benefiting from salvage surgery. Consequently, palliative treatments play a crucial role in managing these cancers. Interventional radiology techniques are well-known for providing significant benefits to patients. [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid is a novel transarterial radioembolization formulation designed for selective arterial injection to deliver localized radiation treatment of advanced unresectable liver tumors. This study aimed to confirm the stability of [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid, investigate its biodistribution in an animal model, and conduct an initial dosimetry evaluation.
Results
Less than 3% of 90Y was released from the [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid formulation in human serum. The tumor-to-liver activity ratio (T/NT) expressed in %ID/g tissue at 1 h, 24 h, 3 days, and 6 days (5.50 ± 2.42, 3.28 ± 1.94, 4.89 ± 3.41 and 4.77 ± 1.59, respectively) suggests effective targeting of tumor tissue compared to healthy liver tissue. The extrapolated absorbed doses in Gy in humans to the tumor, normal liver, lung, and red marrow per GBq of [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid administered were 54.3, 16.2, 0.69 and 0.89, for males, and 54.3, 22.3, 0.84 and 0.89, respectively, for females.
Conclusion
With good in vitro stability at low activity lasting at least 3 half-lives and a T/NT ratio of 4 in vivo, [90Y]Y-L4-Lipo/Lipiodol® Ultra-Fluid is confirmed as a valid candidate treatment for transarterial radioembolization of hepatocellular carcinoma. High activity stability in both in vitro and in vivo studies is needed to complete the formulation’s safety profile.
背景：尽管最近的治疗取得了进展，但对许多国家来说，肝癌的治疗仍然是一个重要的医疗和经济重点。患者往往出现在晚期，阻止他们从抢救手术中获益。因此，姑息治疗在治疗这些癌症中起着至关重要的作用。介入放射学技术为患者提供了显著的益处。[90Y]Y-L4-Lipo/Lipiodol®Ultra-Fluid是一种新型经动脉放射栓塞制剂，用于选择性动脉注射，为晚期不可切除的肝脏肿瘤提供局部放射治疗。本研究旨在证实[90Y]Y-L4-Lipo/Lipiodol®Ultra-Fluid的稳定性，研究其在动物模型中的生物分布，并进行初步剂量学评价。结果：[90Y]Y-L4-Lipo/Lipiodol®超流体制剂在人血清中释放的90Y不到3%。1 h、24 h、3 d、6 d %ID/g组织中表达的瘤肝活性比（T/NT）分别为5.50±2.42、3.28±1.94、4.89±3.41和4.77±1.59，表明与健康肝组织相比，肿瘤组织具有有效的靶向性。[90Y]Y-L4-Lipo/Lipiodol®Ultra-Fluid每GBq对人体肿瘤、正常肝脏、肺和红骨髓的吸收剂量外推为男性54.3、16.2、0.69和0.89，女性54.3、22.3、0.84和0.89。结论：[90Y]Y-L4-Lipo/Lipiodol®Ultra-Fluid在低活性下具有良好的体外稳定性，至少持续3个半衰期，体内T/NT比值为4，被证实是肝细胞癌经动脉放射栓塞治疗的有效候选治疗方法。需要在体外和体内研究中具有高活性稳定性，以完成配方的安全性。
{"title":"[90Y]Y-L4-Lipo/ ethyl esters of Iodized fatty acids of poppy seed oil (lipiodol® ultra-fluid), a new TARE formulation, designed from a lipophilic ligand for stability and safety","authors":"Olivier Fougère, Anne Dencausse, Nicolas Lepareur, Gaetan Van Simaeys, Gilles Doumont, Isabelle Gardin, Elisabeth Renard, Claire Hollenbeck, Coraline De Maeseneire, Nicolas Passon, Olivier Rousseaux, Sarah Catoen","doi":"10.1186/s41181-025-00352-9","DOIUrl":"10.1186/s41181-025-00352-9","url":null,"abstract":"<div><h3>Background</h3><p>Despite recent therapeutic advances, managing liver cancer remains a significant medical and economic priority for many countries. Patients often present at an advanced stage, preventing them from benefiting from salvage surgery. Consequently, palliative treatments play a crucial role in managing these cancers. Interventional radiology techniques are well-known for providing significant benefits to patients. [<sup>90</sup>Y]Y-L4-Lipo/Lipiodol<sup>®</sup> Ultra-Fluid is a novel transarterial radioembolization formulation designed for selective arterial injection to deliver localized radiation treatment of advanced unresectable liver tumors. This study aimed to confirm the stability of [<sup>90</sup>Y]Y-L4-Lipo/Lipiodol<sup>®</sup> Ultra-Fluid, investigate its biodistribution in an animal model, and conduct an initial dosimetry evaluation.</p><h3>Results</h3><p>Less than 3% of <sup>90</sup>Y was released from the [<sup>90</sup>Y]Y-L4-Lipo/Lipiodol<sup>®</sup> Ultra-Fluid formulation in human serum. The tumor-to-liver activity ratio (T/NT) expressed in %ID/g tissue at 1 h, 24 h, 3 days, and 6 days (5.50 ± 2.42, 3.28 ± 1.94, 4.89 ± 3.41 and 4.77 ± 1.59, respectively) suggests effective targeting of tumor tissue compared to healthy liver tissue. The extrapolated absorbed doses in Gy in humans to the tumor, normal liver, lung, and red marrow per GBq of [<sup>90</sup>Y]Y-L4-Lipo/Lipiodol<sup>®</sup> Ultra-Fluid administered were 54.3, 16.2, 0.69 and 0.89, for males, and 54.3, 22.3, 0.84 and 0.89, respectively, for females.</p><h3>Conclusion</h3><p>With good in vitro stability at low activity lasting at least 3 half-lives and a T/NT ratio of 4 in vivo, [<sup>90</sup>Y]Y-L4-Lipo/Lipiodol<sup>®</sup> Ultra-Fluid is confirmed as a valid candidate treatment for transarterial radioembolization of hepatocellular carcinoma. High activity stability in both in vitro and in vivo studies is needed to complete the formulation’s safety profile.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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