Nuclear medicine and biology最新文献

{"title":"Longitudinal multi-tracer imaging of hepatocellular carcinoma identifies novel stage- and oncogene-specific changes","authors":"Mari Teuter ,&nbsp;Yuhai Hu ,&nbsp;Tobias L. Ross ,&nbsp;Kelsey Lolatte ,&nbsp;Michael Ott ,&nbsp;Frank M. Bengel ,&nbsp;Asha Balakrishnan ,&nbsp;Jens P. Bankstahl","doi":"10.1016/j.nucmedbio.2025.109000","DOIUrl":"10.1016/j.nucmedbio.2025.109000","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, globally. There is a need for novel biomarkers for early detection and novel, effective targeted therapies. Molecular imaging can faithfully visualize, characterize and quantify specific relevant biological processes.</div></div><div><h3>Basic procedure</h3><div>We performed longitudinal dedicated small-animal positron emission tomography–computed tomography (PET/CT) imaging to analyze changes in glucose metabolism using [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG), amino acid turnover with [¹⁸F]fluoroethyltyrosine ([¹⁸F]FET), and chemokine receptor expression using [⁶⁸Ga]pentixafor targeting CXCR4, during stages of early tumor development, overt HCC and regression. We used two conditional transgenic mouse models of HCC, driven by clinically relevant oncogenes c-MYC (LT2/MYC) or HRASV12 (LT2/RAS). Conditional doxycycline-regulated mouse models, enable liver-specific oncogene activation or inhibition, leading to liver tumor development and regression, respectively. Correlation of our PET/CT findings with our gene expression and metabolomics data and with histological analyses followed.</div></div><div><h3>Main findings</h3><div>We show PET/CT identifies HCC stage-specific and oncogene-specific molecular changes that may serve as potential novel biomarkers and therapeutic targets. Glucose metabolism and CXCR4 chemokine expression are differentially deregulated during HCC development in an oncogene-specific manner. Our [¹⁸F]FDG results correlated with glucose transporter GLUT1 gene expression and with our metabolomics data. Increased expression of CXCR4 and CD68 inflammatory markers mirrored [⁶⁸Ga]pentixafor results in LT2/MYC mice. FET-based measurement of amino acid turnover are insensitive to stages of HCC-development, in our studies. Concurrently, no significant changes in expression of tyrosine metabolism genes were observed.</div></div><div><h3>Principal conclusions</h3><div>Our study highlights that identified changes in targeted molecular imaging can facilitate a better understanding of underlying biological processes and may help guide novel oncogene-specific targeted anti-tumor therapies in HCC, with promising translational potential.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 109000"},"PeriodicalIF":3.6,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the fate of Zirconium-89 labelled antibody in cynomolgus macaques","authors":"Takanori Sasaki ,&nbsp;Sadaaki Kimura ,&nbsp;Akihiro Noda ,&nbsp;Yoshihiro Murakami ,&nbsp;Sosuke Miyoshi ,&nbsp;Masaru Akehi ,&nbsp;Kazuhiko Ochiai ,&nbsp;Masami Watanabe ,&nbsp;Takahiro Higuchi ,&nbsp;Eiji Matsuura","doi":"10.1016/j.nucmedbio.2025.109001","DOIUrl":"10.1016/j.nucmedbio.2025.109001","url":null,"abstract":"<div><h3>Background</h3><div>Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of ⁸⁹Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies.</div></div><div><h3>Methods</h3><div>Selected IgG was conjugated to desferrioxamine (DFO), labelled with ⁸⁹Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, ⁸⁹Zr-labelled Fab, as well as that of [⁸⁹Zr]Zr-DFO and [⁸⁹Zr]Zr-oxalate, the expected metabolites of ⁸⁹Zr- labelled IgG, was also assessed.</div></div><div><h3>Results</h3><div>After ⁸⁹Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the ⁸⁹Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the ⁸⁹Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in ⁸⁹Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [⁸⁹Zr]Zr-DFO was rapidly excreted into the urine, whereas [⁸⁹Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body.</div></div><div><h3>Conclusion</h3><div>In the non-human primate cynomolgus macaque, ⁸⁹Zr- labelled IgG accumulated in the kidneys and the liver. However, [⁸⁹Zr]Zr-DFO and ⁸⁹Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of ⁸⁹Zr- labelled IgG.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 109001"},"PeriodicalIF":3.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiolabeling yield dependency of post-dry distillation decay of astatine-211","authors":"Ellinor Hansson ,&nbsp;Chiara Timperanza ,&nbsp;Holger Jensen ,&nbsp;Björn Eriksson ,&nbsp;Sture Lindegren ,&nbsp;Emma Aneheim","doi":"10.1016/j.nucmedbio.2025.108999","DOIUrl":"10.1016/j.nucmedbio.2025.108999","url":null,"abstract":"<div><h3>Aim/introduction</h3><div>Astatine-211 (²¹¹At) is one of the most promising nuclides for targeted alpha therapy. However, while several clinical trials are ongoing worldwide, some aspects of the element remain unexplored. This work aims to investigate changes in radiochemical yield over time, expressed as the number of ²¹¹At decays, post-dry distillation using two common astatination reactions.</div></div><div><h3>Materials and methods</h3><div>²¹¹At was purified from activated bismuth targets via dry distillation and eluted in chloroform. The solvated activity was then either evaporated to dryness or left in the chloroform eluate. Before chemical reactions, both forms of the starting material were allowed to age at room temperature for up to 28 h, correlating to 3 ∙ 10^{12 211}At decays. All chemical reactions were subsequently started from a dry residue. Radiolabeling was carried out either via electrophilic destannylation of tri(methyl)phenylstannane, or via the nucleophilic substitution of bis(4-<em>tert</em>-butylphenyl)iodonium <em>p</em>-toluenesulfonate. Radiochemical yield was determined using a dual flow radiodetection HPLC method allowing direct yield quantification.</div></div><div><h3>Results</h3><div>In both cases, where ²¹¹At was stored either as a dry residue or in chloroform, radiochemical yields decreased with increasing amounts of radioactive decay. This was true both for nucleophilic and electrophilic astatinations. In the case of ²¹¹At stored in chloroform, the dose-yield relationship indicates a more rapid decrease for electrophilic astatination. However, decreases in radiochemical yield could be mitigated by increasing the precursor concentration, keeping yields constant above 80 % even when using ²¹¹At after 28 h, corresponding up to 3 ∙ 10^{12 211}At decays. There is also an indication that higher amounts of oxidizing/reducing agents and redissolution of dry ²¹¹At in fresh chloroform may mitigate the loss in yield to some extent.</div></div><div><h3>Conclusion</h3><div>Radiochemical yields in labeling with ²¹¹At decrease over time post dry distillation independent if the ²¹¹At was kept dry or in chloroform. If high specific activity is a requirement for the final radiolabeled product, the most reliable way to maintain high yields is to perform the radiolabeling close in time after the dry distillation.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 108999"},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terbium-161 in nuclear medicine: Preclinical and clinical progress in comparison with lutetium-177","authors":"František Trejtnar ,&nbsp;Pavel Bárta ,&nbsp;Ján Kozempel ,&nbsp;Martin Vlk ,&nbsp;Anna Ďurinová ,&nbsp;Monika Kuchařová ,&nbsp;Petr Pávek","doi":"10.1016/j.nucmedbio.2025.108998","DOIUrl":"10.1016/j.nucmedbio.2025.108998","url":null,"abstract":"<div><div>The use of new radiopharmaceuticals labeled with lutetium-177 represents a successful translation of experimental results into clinical practice. Recent experimental data suggests that terbium-161 might well follow the example of lutetium-177 regarding applicability in nuclear medicine. Similarly to lutetium-177, the terbium-161 emits beta particles and gamma-radiation, although terbium-161 emits short-ranged conversion and Auger electrons, creating an effect that may eliminate smaller tumor metastases more effectively than lutetium-177. Terbium-161 may exert a higher radiobiological effect in the target tissues in comparison with lutetium-177, a difference which makes possible a reduction in the doses of radioactivity administered. Further, due to the similar chemical properties of lutetium-177 and terbium-161, similar radiolabeling techniques can be used. The differences found in preclinical experiments on radiotoxicity of the counterparts seem to be minor. Despite intensive progress, the number of preclinical studies on ¹⁶¹Tb-labeled agents is still not comparable to studies on lutetium-177. Clinical trials with ¹⁶¹Tb-labeled radiopharmaceuticals focused on the treatment of prostate cancer and selected neuroendocrine tumors have already begun, although none of them have been completed yet.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 108998"},"PeriodicalIF":3.6,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436479","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}

{"title":"Production and purification of radiolabeling-ready 132/135La from the irradiation of metallic natBa targets with low energy protons","authors":"E.S. Kurakina ,&nbsp;B.L. McNeil ,&nbsp;J. Khushvaktov ,&nbsp;N.T. Temerbulatova ,&nbsp;N.A. Mirzayev ,&nbsp;E.P. Magomedbekov ,&nbsp;C. Hoehr ,&nbsp;C.F. Ramogida ,&nbsp;D.V. Filosofov ,&nbsp;V. Radchenko","doi":"10.1016/j.nucmedbio.2025.108994","DOIUrl":"10.1016/j.nucmedbio.2025.108994","url":null,"abstract":"<div><h3>Introduction</h3><div>Radiolanthanides ¹³²La and ¹³⁵La form a promising chemically matched theranostic pair. With a half-life of 18.95 h, ¹³⁵La acts as the therapeutic isotope as it releases approximately 11 Auger electrons per decay, making it compatible with targeted Auger electron therapy (TAET), whereas ¹³²La with half-life of 4.58 h undergoes positron emission making it compatible with imaging via positron emission tomography (PET).</div></div><div><h3>Methods</h3><div>^132/135La were produced via irradiation of natural barium targets (99.9 %) with 12.8 MeV protons. A two-step separation scheme using extraction chromatographic resin TK200 (50–100 μm) and cation exchange resin Dowex 50Wx4 (200–400 mesh) was designed. Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify non-radioactive impurities in each fraction of the separation method. The distribution coefficients of La³⁺ in HNO₃ on the TK200 resin and on both Dowex 50Wx8 (200–400 mesh) and Dowex 50Wx4 resins in ammonium α-hydroxyisobutyrate (pH 4.8) were determined, respectively.</div></div><div><h3>Results</h3><div>This novel separation scheme allowed for reliable separation of [^132/135La]La³⁺ from the Ba²⁺ target material, resulting in a high radiochemical yield of 98.3 ± 2.1 % (<em>n</em> = 3) with the final elute being directly compatible with subsequent radiolabeling due to the use of ammonium α-hydroxyisobutyrate to eliminate steps in the radiopharmaceutical synthetic process.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 108994"},"PeriodicalIF":3.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075026","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}

{"title":"Quantitative imaging using [18F]F-TZ3108 to assess metabolic-associated fatty liver disease progression and low-carbohydrate diet efficacy","authors":"Zongping Han ,&nbsp;Min Yang ,&nbsp;Lei Bi ,&nbsp;Peizhen Ye ,&nbsp;Yongshan Liu ,&nbsp;Pengyuan He ,&nbsp;Guolong Huang ,&nbsp;Hongjun Jin ,&nbsp;Jinyu Xia","doi":"10.1016/j.nucmedbio.2025.108997","DOIUrl":"10.1016/j.nucmedbio.2025.108997","url":null,"abstract":"<div><h3>Objective</h3><div>The Sigma-1 receptor (Sig-1R), located in the mitochondrion-associated membranes (MAMs), is an important biomarker for endoplasmic reticulum (ER) stress and plays a crucial role in the advancement of metabolic-associated fatty liver disease (MAFLD). Despite its significance, current methods to monitor MAFLD progression and treatment response are limited. This study aims to address this gap by utilizing [¹⁸F]F-TZ3108, an effecient tracer targeting Sig-1R, to quantitatively assess MAFLD progression and the efficacy of a low-carbohydrate diet (LCD) as a potential therapeutic intervention.</div></div><div><h3>Methods</h3><div>The C57 BL/6 J mice were fed either a high-fat diet (HFD) or regular diet (CTR) for 12 weeks, and the progression of MAFLD was continuously monitored at 0, 4, 8, 12 weeks via [¹⁸F]F-TZ3108 positron emission tomography/computed tomography (PET/CT) and ex vivo assessment. After confirming successful induction, LDC intervention was administered in the HFD group for 2 weeks. And relevant post-treatment evaluations were also performed.</div></div><div><h3>Results</h3><div>PET/CT revealed a continuous decline in the hepatic binding potential (BP_ND) of [¹⁸F]F-TZ3108 in mice in the HFD group during the induction period, when compared with the BP_ND in the CTR group. This reduction was significant after the 4th week of induction (<em>p</em> &lt; 0.05). Furthermore, following intervention with LCD, there was a significant improvement in BP_ND (LCD vs HFD, <em>p</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>The results of this study demonstrate that LCD therapy effectively mitigates MAFLD progression. Furthermore, the use of PET imaging with [¹⁸F]F-TZ3108 provides a reliable, non-invasive method for monitoring the progression and treatment response of MAFLD, offering significant potential for early detection and personalized treatment evaluation.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"144 ","pages":"Article 108997"},"PeriodicalIF":3.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350265","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}

{"title":"[18F]BCPP-EF positron emission tomography of rat ovaries for evaluation of mitochondrial function","authors":"Yuki Tomonari,&nbsp;Hiroyuki Ohba,&nbsp;Hideo Tsukada","doi":"10.1016/j.nucmedbio.2025.108996","DOIUrl":"10.1016/j.nucmedbio.2025.108996","url":null,"abstract":"<div><h3>Background</h3><div>The ovary is an important female organ not only for pregnancy but also for the regulation of life activities via hormone release. Ovarian function is measured by blood hormone levels, but the hormone level reflects only the ovarian reserve and no other essential ovarian functions, such as nurturing and expelling follicles. Ovarian fibrosis is related to essential ovarian function; however, the existing methods for evaluating fibrosis are invasive. Ovarian fibrosis has been reported to be associated with mitochondrial function. We hypothesized that positron emission tomography (PET) imaging of mitochondria could be a new, non-invasive method for evaluating essential ovarian function. In this study, we investigated the age-related changes in ovarian fibrosis using the mitochondrial complex-I (MC-I) PET probe, 2-<em>tert</em>-butyl-4-chloro-5-{6-[2-(2-¹⁸F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([¹⁸F]BCPP-EF).</div></div><div><h3>Results</h3><div>Aged rats, whose ovary function decline, exhibited a higher uptake of [¹⁸F]BCPP-EF in the ovary than young rats, and this high uptake in aged rats was suppressed by mitoquinone, a superoxide scavenger. Increased [¹⁸F]BCPP-EF uptake in the ovary was associated with ovarian fibrosis, but not with AMH level which reflects the ovarian reserve. Furthermore, the measurement of MC protein levels showed that the protein levels of MC-I increased with age, whereas those of MC-V decreased.</div></div><div><h3>Conclusions</h3><div>This study demonstrated that [¹⁸F]BCPP-EF can detect age-related changes in essential ovarian function evaluated by ovarian fibrosis. Therefore, [¹⁸F]BCPP-EF-PET is a useful non-invasive method for evaluating essential ovarian functions and will contribute to basic research on ovarian aging as well as drug discovery targeting ovarian dysfunction.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108996"},"PeriodicalIF":3.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040129","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}

{"title":"Cross sections of the 226Ra(p,xn) reactions relevant for 225Ac production","authors":"Ondřej Lebeda,&nbsp;Kateřina Ondrák Fialová,&nbsp;Lukáš Ondrák,&nbsp;Jaroslav Červenák,&nbsp;Jan Ráliš,&nbsp;Jan Štursa","doi":"10.1016/j.nucmedbio.2025.108995","DOIUrl":"10.1016/j.nucmedbio.2025.108995","url":null,"abstract":"<div><div>Limited availability constrains the implementation of ²²⁵Ac, the most promising α emitter for targeted therapy, in clinical practice. Proton activation of ²²⁶Ra is one of few realistic solutions to this problem. We have therefore measured cross sections of relevant ²²⁶Ra(<em>p,xn</em>) nuclear reactions in the energy range of 12.0 to 17.2 MeV. The obtained results allowed us to deduce the yield of ²²⁴Ac, ²²⁵Ac, and ²²⁶Ac. The consequences of our data to predictions of production capacity and radionuclidic purity of ²²⁵Ac are thoroughly discussed, and their comparison with previous measurements and with the prediction of the TALYS 1.96 nuclear reaction model code run with default parameters are provided.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108995"},"PeriodicalIF":3.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029254","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}

{"title":"First-in-human healthy volunteer dosimetry studies of the excitatory amino acid transporter 2 (EAAT2) PET imaging tracer methyl N4-(7-[18F]fluoro-9H-fluoren-2-yl)asparaginate, [18F]RP-115","authors":"Chih-Kai Chao ,&nbsp;Joseph Blecha ,&nbsp;Ilona Polvoy ,&nbsp;Ryan Michael Nillo ,&nbsp;Youngho Seo ,&nbsp;David M. Wilson ,&nbsp;John R. Forsayeth ,&nbsp;Henry F. VanBrocklin ,&nbsp;John M. Gerdes","doi":"10.1016/j.nucmedbio.2025.108992","DOIUrl":"10.1016/j.nucmedbio.2025.108992","url":null,"abstract":"<div><h3>Objective and background</h3><div>The objective of this first-in-human study was to investigate the radiosynthesis, and the preliminary safety, biodistribution, and organ radiation dosimetry of the positron emission tomography (PET) imaging tracer methyl <em>N</em>⁴-([¹⁸F]7-fluoro-9<em>H</em>-fluoren-2-yl)asparaginate, known as [¹⁸F]RP-115, in a small cohort (n=8) of healthy volunteers. The [¹⁸F]RP-115 tracer is a methyl ester prodrug and undergoes metabolic saponification in the central nervous system to generate the corresponding carboxylic acid form that selectively binds to the excitatory amino acid transporter 2 (EAAT2) protein.</div></div><div><h3>Procedures and methods</h3><div>A multi-step high molar activity tracer radiosynthesis was devised to produce doses. Eight healthy human participants (four male and four female), aged 56–75, received a bolus intravenous injection of [¹⁸F]RP-115 (administered activity range: 70.3–355 MBq) prior to a total of 94 min of PET-MR scanning performed as three sequential scanning sessions. Regional tissue volumes of interest were defined, time-integrated activity coefficients (TIAC) were derived, and then estimates of organ and tissue activities and effective doses (whole body) were calculated, with two versions of OLINDA software (1.1 and 2.0) that incorporated two tissue weighting factor sets (ICRP-60 and -103), respectively.</div></div><div><h3>Main findings</h3><div>Tracer was routinely produced in good radiochemical yields and as suitable high molar activity doses for injection. The [¹⁸F]RP-115 injections and PET-MR scans were well-tolerated and no adverse events were reported (≤48 h). Radioactivity was widely biodistributed with good organ uptake. TIACs and estimated radiation organ doses were determined, for which a few statistically significant estimated organ dose differences between males and females were noted. The kidneys were identified as the critical target organ.</div></div><div><h3>Principal conclusions</h3><div>Injection of [¹⁸F]RP-115 was considered safe. The estimated kidney radiation doses relative to administered radioactivity identified a more optimal human [¹⁸F]RP-115 tracer injected amount of &lt;211 MBq. This more optimal [¹⁸F]RP-115 tracer injected activity definition is similar to the amounts used for other established [¹⁸F]labeled clinical PET tracers such as [¹⁸F]FDG, and it will be used in future RP-115 clinical PET imaging studies.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108992"},"PeriodicalIF":3.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143328928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a novel PET radioligand for mitochondrial complex I in nonhuman primate","authors":"Yulong Xu ,&nbsp;Yiming Xu ,&nbsp;Frederick Andrew Bagdasarian ,&nbsp;Tewodros Mulugeta Dagnew ,&nbsp;Hua Cheng ,&nbsp;Yanli Wang ,&nbsp;Yongle Wang ,&nbsp;Leyi Kang ,&nbsp;Hsiao-Ying Wey ,&nbsp;Can Zhang ,&nbsp;Shijun Zhang ,&nbsp;Changning Wang","doi":"10.1016/j.nucmedbio.2025.108993","DOIUrl":"10.1016/j.nucmedbio.2025.108993","url":null,"abstract":"<div><div>The role of mitochondrial complex I (MC-I) dysfunction is well-documented across a range of neurodegenerative disorders. Recently, a novel positron emission tomography (PET) radioligand, [¹⁸F]CNL02, has been synthesized to target MC-I. In this paper, we provide a comprehensive characterization of [¹⁸F]CNL02, using nonhuman primate as a model system. In the brain of a rhesus macaque, [¹⁸F]CNL02 demonstrated specific binding in regions expressing MC-I. All observed brain regions showed rapid kinetic profiles. Analysis of arterial plasma indicated a swift clearance of [¹⁸F]CNL02 from the bloodstream. Metabolite analysis identified two predominant radiometabolites in the plasma. The regional brain time-activity curves (TACs) for [¹⁸F]CNL02 were effectively characterized through a two-tissue compartment model (2TCM). Furthermore, the total distribution volume was reliably estimated employing the Logan plot method. Consequently, continued development and refinement of [¹⁸F]CNL02 are imperative.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"142 ","pages":"Article 108993"},"PeriodicalIF":3.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009022","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}