EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Development and evaluation of a ^99mTc-labeled olaparib analog for PARP imaging.","authors":"Wei Xu, Junjie Yan, Xinlin Zhong, Donghui Pan, Xinyu Wang, Yuping Xu, Lizhen Wang, Chongyang Chen, Min Yang","doi":"10.1186/s41181-025-00373-4","DOIUrl":"https://doi.org/10.1186/s41181-025-00373-4","url":null,"abstract":"<p><strong>Background: </strong>Poly(ADP-ribose) polymerase (PARP) is an important therapeutic target in cancer treatment, and dynamic assessment of its expression level is essential for achieving precision therapy. Although ¹⁸F-labeled PARP-targeted radiotracers have demonstrated remarkable tumor-imaging capabilities in preclinical studies, their high lipophilicity leads to increased non-specific uptake in abdominal organs, which has severely hindered their clinical translation. Furthermore, while PET imaging provides superior resolution and sensitivity, its infrastructure and operational demands may limit widespread accessibility in certain regions. Therefore, the development of SPECT-based PARP radiotracers could offer a complementary approach, potentially expanding access to PARP imaging in a broader range of clinical settings. To provide a more affordable and accessible alternative to PET probes, hydrazinonicotinamide (HYNIC)-olaparib was radiolabeled with technetium-99m (^99mTc) and evaluated both in vitro and in vivo using the MDA-MB-453 breast cancer model.</p><p><strong>Results: </strong>[^99mTc][Tc-HYNIC/EDDA]-olaparib exhibits a high radiochemical yield (> 90%), excellent radiochemical purity (> 90%), and good in vitro stability. The introduction of ethylenediamine-N, N'-diacetic acid (EDDA) and tricine facilitated the synthesis of ^99mTc complex, and improved the hydrophilicity (logP = 0.63 ± 0.25) of the probe as well, resulting in reduced the accumulation of radiation in the abdomen. In vitro results indicated that [^99mTc][Tc-HYNIC/EDDA]-olaparib could target PRAP-1 in MDA-MB-453 cells. In vivo experiments, micro SPECT/CT imaging provided clear visualization of MDA-MB-453 tumors with significant tumor-to-background distinction, and accumulation of [^99mTc][Tc-HYNIC/EDDA]-olaparib was quantified at 3.45 ± 0.17%ID/g at 1 h post intravenous injection.</p><p><strong>Conclusion: </strong>These findings suggest that [^99mTc][Tc-HYNIC/EDDA]-olaparib holds great promise as a novel radiotracer for PARP imaging.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"46"},"PeriodicalIF":4.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifactorial analysis of radiochemical purity in high-activity ¹⁷⁷Lu-labeled theranostics: impact of precursor source, ¹⁷⁷Lu form, and production parameters.","authors":"William Hunt, Mathew Long, Usama Kamil, Sunil Kellapatha, Wayne Noonan, Peter D Roselt, Nathan Papa, Brittany Emmerson, Michael S Hofman, Mohammad B Haskali","doi":"10.1186/s41181-025-00372-5","DOIUrl":"https://doi.org/10.1186/s41181-025-00372-5","url":null,"abstract":"<p><strong>Background: </strong>Lutetium-177 (¹⁷⁷Lu) theranostics have revolutionized personalized cancer treatment, particularly with FDA-approved therapies like [¹⁷⁷Lu]Lu-DOTA-TATE for neuroendocrine tumors and [¹⁷⁷Lu]Lu-PSMA for prostate cancer. Despite growing clinical adoption, there is limited understanding of how different production variables affect radiochemical purity, especially when scaling to high activities for multi-patient batches. This study evaluates the impact of precursor sources, ¹⁷⁷Lu forms (carrier-added (C.A) vs. non- carrier-added (N.C.A)), and radiochemical concentration on product quality.</p><p><strong>Results: </strong>We analyzed 355 clinical batches of [¹⁷⁷Lu]Lu-DOTA-TATE (n = 101), [¹⁷⁷Lu]Lu- PSMA-617 (n = 169), and [¹⁷⁷Lu]Lu-PSMA-I&T (n = 85) produced with standardized protocols using lutetium-177 from multiple suppliers in both carrier-added and non-carrier-added forms. All radiopharmaceuticals demonstrated consistently high yields (≥ 98%) and met release criteria regardless of starting materials. [¹⁷⁷Lu]Lu-DOTA-TATE and [¹⁷⁷Lu]Lu-PSMA-617 maintained radiochemical purity above 90% throughout 24 h, while [¹⁷⁷Lu]Lu-PSMA-I&T showed stability for 8 h but fell below specifications at 24 h. Negative correlations between bulk activity/concentration and radiochemical purity were observed across all preparations. The lutetium-177 products from various suppliers displayed notably distinct quality profiles. Some suppliers consistently provided higher radiochemical purities, irrespective of the carrier-added or non-carrier-added forms of lutetium-177. However, carrier- added formulations exhibited greater radiostability compared to non-carrier-added ones at elevated concentrations. Furthermore, differences in precursor quality among manufacturers were noted, with certain suppliers offering enhanced radiostability characteristics that may enhance product performance at high activity concentrations.</p><p><strong>Conclusion: </strong>This comprehensive analysis reveals that hospital-based production can be automized resulting in high-quality and efficient multi-dose production. Small differences in radiochemical purity of ¹⁷⁷Lu -labeled theranostics depends on complex interactions between precursor source, ¹⁷⁷Lu supplier, and ¹⁷⁷Lu form, beyond simple activity-dependent radiolysis. These findings underscore the importance of optimizing production parameters for high- activity preparations and highlight the need to explore the various multifactorial variables that impact the quality of ¹⁷⁷Lu-theranostics.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"47"},"PeriodicalIF":4.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Auger electron-emitting EGFR-targeted and non-targeted [¹⁹⁷Hg]Hg-gold nanoparticles for treatment of glioblastoma multiforme (GBM).","authors":"Madeline K Brown, Zhongli Cai, Constantine J Georgiou, Shaohuang Chen, Yumeela Ganga-Sah, Valery Radchenko, James T Rutka, Raymond M Reilly","doi":"10.1186/s41181-025-00367-2","DOIUrl":"10.1186/s41181-025-00367-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;We describe here radiation nanomedicines for glioblastoma multiforme (GBM) composed of gold nanoparticles (AuNPs) that integrate the Auger electron-emitter, &lt;sup&gt;197&lt;/sup&gt;Hg. [&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs were conjugated to anti-epidermal growth factor receptor (EGFR) panitumumab or were non-targeted. Our aim was to compare the cytotoxicity and DNA-damaging properties in vitro of panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs and non-targeted [&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs on U251-Luc human GBM cells and estimate their cellular dosimetry. We further aimed to compare the biodistribution in vivo of panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs and [&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs after convection-enhanced delivery (CED) in NRG mice with U251-Luc tumours in the brain and estimate the absorbed doses in the tumour and surrounding margins of healthy brain.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs (26.8 ± 6.4 nm) were produced with a radiochemical yield of 98 ± 1% by incorporating &lt;sup&gt;197&lt;/sup&gt;Hg into the Turkevich synthesis method, forming a mercury-gold amalgam. Panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs exhibited high affinity (K&lt;sub&gt;D&lt;/sub&gt; = 1.8 × 10&lt;sup&gt;-9&lt;/sup&gt; mol/L) binding to EGFR-positive U251-Luc cells. The binding of panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs to U251-Luc cells was 15-fold higher than [&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs, and internalization and nuclear uptake were 12-fold and 18-fold greater, respectively. Panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs caused 84-fold more DNA double-strand breaks (DSBs) in U251-Luc cells than [&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs. Panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs were ninefold more effective at reducing the clonogenic survival of U251-Luc cells than [&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs. Panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs were twofold more cytotoxic than non-radioactive panitumumab-AuNPs (P = 0.04) and fivefold more cytotoxic than panitumumab (P = 0.01). The absorbed doses in the nucleus of U251-Luc cells treated in vitro with panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs or [&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs were 8.8 ± 2.9 Gy and 0.6 ± 0.1 Gy, respectively. SPECT/CT imaging showed that panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs and [&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs were strongly retained at the infusion site in the brain after CED up to 7 d in NRG mice with orthotopic U251-Luc tumours. Uptake of panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs in the tumour-bearing right hemisphere [484.5% injected dose/g (%ID/g)] was 172-fold and 579-fold greater than in the healthy left hemisphere and cerebellum, respectively. The uptake of [&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs (423.9% ID/g) in the tumour-bearing right hemisphere was 85-fold and 64-fold higher than the left hemisphere and cerebellum, respectively. Most normal tissue uptake was &lt; 1% ID/g, except for kidneys (9-20% ID/g), spleen (3.5-6.6% ID/g) and liver (0.6-3.3% ID/g). Dosimetry showed that 58% of the tumour received &gt; 190 Gy for CED of 1.0 MBq of panitumumab-[&lt;sup&gt;197&lt;/sup&gt;Hg]Hg-AuNPs vs. 0.6% of ","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"45"},"PeriodicalIF":4.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658012","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}

{"title":"PET imaging of platelet derived growth factor receptor β in lung fibrosis.","authors":"Olivia Wegrzyniak, Francesco Lechi, Johanna Rokka, Bogdan Mitran, Bo Zhang, Ulrika Thelander, John Löfblom, Fredrik Y Frejd, Olle Korsgren, Gaetano Perchiazzi, Jonas Eriksson, Olof Eriksson","doi":"10.1186/s41181-025-00366-3","DOIUrl":"10.1186/s41181-025-00366-3","url":null,"abstract":"<p><strong>Background: </strong>Lung diseases such as idiopathic pulmonary fibrosis and acute respiratory distress syndrome (ARDS) are associated with significant morbidity and mortality, with limited treatment options. Platelet-derived growth factor receptor beta (PDGFRβ) signaling pathway is a key driver of fibrogenesis in different organs. In the lungs, pericytes have a high PDGFRβ expression, and their role as immune regulators and progenitors of myofibroblasts is increasingly recognized. Non-invasive techniques to assess active lung tissue remodeling are needed to improve disease monitoring and treatment evaluation. This study aimed to evaluate [¹⁸F]TZ-Z09591, targeting PDGFRβ, for imaging pulmonary injuries in human biopsies, and in vivo in animal models of lung injury.</p><p><strong>Results: </strong>[¹⁸F]TZ-Z09591 demonstrated high and specific binding to PDGFRβ-expressing cells. Autoradiography confirmed tracer uptake in lung injuries, including fibrotic foci, from human, rat, and pig lung tissues. In vivo positron emission tomography (PET) imaging of bleomycin-induced lung fibrosis in rats and an ARDS pig model showed significantly increased uptake in diseased lung segments compared to controls, especially in pulmonary injuries with collagen deposition, despite moderate background uptake.</p><p><strong>Conclusions: </strong>This study demonstrated that [¹⁸F]TZ-Z09591 can assess PDGFRβ expression in pulmonary injuries, supporting its potential for non-invasive assessment of lung tissue remodeling. PET imaging targeting PDGFRβ could improve disease monitoring, and provide new insights into pulmonary fibrosis progression.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"44"},"PeriodicalIF":4.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641435","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}

{"title":"Development of a halofluorocarbon, chromatography-free radiosynthesis of fluorine-18 difluorocarbene.","authors":"Catherine G F Dickmann, Andrew D Bond, Selena Milicevic Sephton, Franklin I Aigbirhio","doi":"10.1186/s41181-025-00353-8","DOIUrl":"10.1186/s41181-025-00353-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In recent years, the development of the [&lt;sup&gt;18&lt;/sup&gt;F]difluoromethyl radical ([&lt;sup&gt;18&lt;/sup&gt;F]2-((difluoromethyl)sulfonyl)benzo[d]thiazole, [&lt;sup&gt;18&lt;/sup&gt;F]4), and [&lt;sup&gt;18&lt;/sup&gt;F]difluorocarbene ([&lt;sup&gt;18&lt;/sup&gt;F]1-chloro-4-((difluoromethyl)sulfonyl)benzene, [&lt;sup&gt;18&lt;/sup&gt;F]10) prosthetic groups, has paved the way towards direct &lt;sup&gt;18&lt;/sup&gt;F-difluoromethylation in routine PET tracer synthesis with high molar activity. However, limitations in their syntheses may be hindering their widespread adoption by the radiochemistry community. Firstly, the synthesis of the precursors 2-((bromofluoromethyl)thio)benzo[d]thiazole (3) and (bromofluoromethyl)(4-chlorophfenyl)sulfane (8) requires the use of the ozone-depleting dibromofluoromethane, a reagent that is not-commercially available. Secondly, the reported syntheses of [&lt;sup&gt;18&lt;/sup&gt;F]4 and [&lt;sup&gt;18&lt;/sup&gt;F]10 are lengthy and require semi-preparative HPLC purification prior to the &lt;sup&gt;18&lt;/sup&gt;F-difluoromethylation step. Finally, in the case of [&lt;sup&gt;18&lt;/sup&gt;F]10, very large amounts of precursor material (200 μmol) are required for difluorocarbene insertion. The aim of this work was to develop a halofluorocarbon-free radiosynthesis of [&lt;sup&gt;18&lt;/sup&gt;F]4 and [&lt;sup&gt;18&lt;/sup&gt;F]10 on the GE TRACERlab FX&lt;sub&gt;FN&lt;/sub&gt; module. Additionally, another aim was to develop a chromatography-free, fully-automated synthesis of [&lt;sup&gt;18&lt;/sup&gt;F]10 on the GE FX&lt;sub&gt;FN&lt;/sub&gt; module.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Precursors 3 and 8 were synthesised in 21% and 54% yield via decarboxylative bromination, which circumvented the need for ozone-depleting dibromofluoromethane. Difluoromethyl reagents [&lt;sup&gt;18&lt;/sup&gt;F]4 and [&lt;sup&gt;18&lt;/sup&gt;F]10 were synthesised on a GE FX&lt;sub&gt;FN&lt;/sub&gt; module with semi-prep HPLC purification in 4% and 3% RCY (decay-corrected), respectively. The synthesis of [&lt;sup&gt;18&lt;/sup&gt;F]10 was further simplified through elimination of the semi-prep HPLC purification in favour of a cartridge-based solid-phase extraction (SPE) trapping and elution approach (on an alumina SPE cartridge loaded in series with a C18 Sep-Pak plus SPE cartridge) to give [&lt;sup&gt;18&lt;/sup&gt;F]10 in 10.1% ± 1.9% (n = 6, decay-corrected) RCY (97% ± 3% RCP, 1.5-11 GBq/μmol). Finally, a fully automated &lt;sup&gt;18&lt;/sup&gt;F-difluoromethylation radiosynthesis with [&lt;sup&gt;18&lt;/sup&gt;F]10 was developed on two GE FX&lt;sub&gt;FN&lt;/sub&gt; modules linked together to yield the model &lt;sup&gt;18&lt;/sup&gt;F-difluoromethylated compound in adequate amounts for biological studies, in under two hours (99.0 MBq, 0.8% RCY {decay-corrected}, 1.5 GBq/μmol, 103 min total synthesis time). Therefore, we have established a path forward for routine automated synthesis of radiotracers via [&lt;sup&gt;18&lt;/sup&gt;F]difluorocarbene insertion with [&lt;sup&gt;18&lt;/sup&gt;F]10.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;A halofluorocarbon, chromatography-free synthesis on the GE FX&lt;sub&gt;FN&lt;/sub&gt; module afforded difluorocarbene reagent [&lt;sup&gt;18&lt;/sup&gt;F]10 in 10.1% ± 1.9% RCY (decay-corrected). Additio","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"43"},"PeriodicalIF":4.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635879","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}

{"title":"To be GMP or not to be- a radionuclide's question.","authors":"Clemens Decristoforo, Renata Mikolajczak, Clive Naidoo, Suzanne Lapi, Ferid Haddad, David Emmanuel Schmid, Lurdes Gano, Ulli Köster, Thierry Stora","doi":"10.1186/s41181-025-00369-0","DOIUrl":"10.1186/s41181-025-00369-0","url":null,"abstract":"<p><strong>Background: </strong>Radionuclides are the essential component of radiopharmaceuticals, their production needs to consider pharmaceutical regulations and guidelines, also for clinical research applications.</p><p><strong>Main body: </strong>In this paper we reflect on the pharmaceutical regulatory landscape for radionuclide production in Europe, with a focus on Good Manufacturing Practices (GMP). The challenges for novel production pathways and the pathways for non-GMP production of radionuclides are discussed.</p><p><strong>Conclusion: </strong>In particular when radionuclides are used as starting materials, exemptions from GMP requirements are essential for clinical innovation and a common understanding is needed to enable the safe use of novel radionuclides for medical applications without unnecessary regulatory hurdles for the user.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"42"},"PeriodicalIF":4.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599049","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}

{"title":"⁶⁸Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage.","authors":"Jona Wilhelm Gerhards, Laura Schäfer, Daniel Kang, Ute Lindauer, Susanne Lütje, Felix Manuel Mottaghy, Tobias Schmidt, Andreas Theodor Josef Vogg","doi":"10.1186/s41181-025-00348-5","DOIUrl":"10.1186/s41181-025-00348-5","url":null,"abstract":"<p><strong>Background: </strong>Aneurysmal subarachnoid hemorrhage (aSAH) is a distinct type of stroke, primarily caused by the rupture of a brain aneurysm. The underlying mechanisms of aSAH remain incompletely understood, prompting ongoing research in this area. Recent investigations into the perivascular system revealed a distribution disturbance of the dye Alexa Fluor™ 594 during measurements. To further investigate this distribution anomaly, it is proposed to label the dye with a radionuclide for biokinetic tracking in rats by means of positron emission tomography for enhanced imaging and analysis.</p><p><strong>Results: </strong>The fluorescent dye Alexa Fluor™ 594 after chelator conjugation was successfully labeled with the positron-emitting radionuclide ⁶⁸Ga(III) in a no-carrier-added form. Initially, the NODA-GA-NHS ester was employed to react with the amino group of Alexa Fluor™ 594 1,5-diaminopentane, facilitating subsequent radiolabeling with ⁶⁸Ga. The formation of the Alexa Fluor™ 594-chelator conjugate, as well as the radiolabeling, were investigated as a function of reaction time and temperature. For potential animal experiments, it was necessary to increase the reaction temperature from room temperature to 80 °C to optimize the reaction conditions, given the short half-life of ⁶⁸Ga. Optimal labeling conditions were established, achieving a radiochemical yield of > 85%. Separation and purification of n.c.a. [⁶⁸Ga]Ga-NODA-GA-Alexa Fluor™ 594 were conducted, with impurities remaining below 3%.</p><p><strong>Conclusions: </strong>This experimental approach successfully yields the desired radiolabeled dye, which is now available for animal studies, potentially offering enhanced insight into the mechanisms of aSAH.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"41"},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599048","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}

{"title":"Rapid cleavage of 6-[¹⁸F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules.","authors":"Pyry Dillemuth, Abiodun Ayo, Xiaoqing Zhuang, Petter Lövdahl, Heidi Liljenbäck, Salli Kärnä, Tatsiana Auchynnikava, Jonne Kunnas, Jesse Ponkamo, Maxwell W G Miner, Johan Rajander, Jessica M Rosenholm, Anne Roivainen, Anu J Airaksinen, Pirjo Laakkonen, Xiang-Guo Li","doi":"10.1186/s41181-025-00368-1","DOIUrl":"10.1186/s41181-025-00368-1","url":null,"abstract":"<p><strong>Background: </strong>Peptides radiolabeled with fluorine-18 are frequently synthesized using prosthetic groups. Among them, activated esters of 6-[¹⁸F]fluoronicotinic acid ([¹⁸F]FNA) have been prepared and successfully employed for ¹⁸F-labeling of diverse biomolecules, including peptides. The utility of [¹⁸F]FNA as a prosthetic compound has been demonstrated in both preclinical and clinical settings, including radiopharmaceuticals targeting prostate-specific membrane antigen and poly(ADP ribose) polymerase inhibitors. This study aims to evaluate a [¹⁸F]FNA-conjugated nonapeptide, [¹⁸F]FNA-N-CooP, for positron emission tomography imaging of intracranial BT12 glioblastoma xenografts in a mouse model. Additionally, this study highlights the importance of including control experiments with prosthetic compound alone when it constitutes a major radiometabolite.</p><p><strong>Results: </strong>[¹⁸F]FNA-N-CooP successfully delineated intracranial glioblastoma xenografts yielding a standardized uptake value of 0.21 ± 0.03 (n = 4) and a tumor-to-brain ratio of 1.84 ± 0.29. Ex vivo autoradiography of tumor tissue showed a partial co-localization between radioactivity uptake and the target fatty acid binding protein 3 expression. However, in vivo instability of [¹⁸F]FNA-N-CooP was observed, with [¹⁸F]FNA identified as a major radiometabolite. Notably, control studies using [¹⁸F]FNA alone also visualized tumors, producing a standardized uptake value of 0.90 ± 0.10 (n = 4) and a tumor-to-brain ratio of 1.51 ± 0.08.</p><p><strong>Conclusions: </strong>Both [¹⁸F]FNA-N-CooP and [¹⁸F]FNA enabled PET visualization of human glioblastoma in the mouse model. However, the prominent presence of [¹⁸F]FNA as radiometabolite complicates the interpretation of [¹⁸F]FNA-N-CooP PET data, suggesting that the observed radioactivity uptake may primarily originate from [¹⁸F]FNA and other radiometabolites. Enhancing peptide stability is essential for improving imaging specificity. This study underscores the critical need to assess the imaging contributions of prosthetic groups when they function as significant radiometabolites.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"40"},"PeriodicalIF":4.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590102","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}

{"title":"Development of new albumin-binding radiotracers for PET imaging of cerebrospinal fluid flow in the glymphatic system.","authors":"Martta Peltoniemi, Surachet Imlimthan, Sonja C Jalonen, Niklas Daniel Åke Persson, Terhi J Lohela, Tuomas O Lilius, Mirkka Sarparanta","doi":"10.1186/s41181-025-00365-4","DOIUrl":"10.1186/s41181-025-00365-4","url":null,"abstract":"<p><strong>Background: </strong>The glymphatic system is a recently discovered brain-wide clearance system that allows the cerebrospinal fluid (CSF) flow to clear metabolic waste, but the tools for the quantitative and non-invasive investigation of its function and activity especially in humans is lacking, hindering studies on glymphatic system physiology and therapeutic potential of glymphatic drug delivery and modulation. We postulated that albumin-binding radiotracers could be used to this end by binding to the endogenous protein in CSF, constituting a macromolecular, biological radiotracer, allowing for the visualization of CSF flow in the central nervous system non-invasively with positron emission tomography (PET).</p><p><strong>Results: </strong>We prepared three albumin-binding tracers based on 4-(p-iodophenyl)butyric acid and truncated Evans Blue radiolabeled with gallium-68 using the NODAGA chelator for in vivo radiolabeling of CSF albumin, and an in vitro radiolabeled reference tracer Al[¹⁸F]F-RESCA-rat serum albumin (RSA) with high radiochemical yield and purity, and acceptable molar activity (A_m). The biological evaluation of the tracers showed high radiolabel stability and rapid binding with albumin in vitro and in vivo with the biological half-life in Swiss mice after intravenous administration matching serum albumin (> 18 h). Dynamic PET imaging in female Sprague Dawley rats under ketamine/dexmedetomidine anesthesia after lumbar and intracisternal infusion showed distribution of the tracers towards intracranial space and along the spinal canal from the infusion site. However, the cervical lymph nodes were only visualized after the infusion of Al[¹⁸F]F-RESCA-RSA, characteristic for macromolecular tracers, indicating that the gallium-68-labeled tracers did not bind fully to endogenous CSF albumin in vivo, but were distributing to different brain areas according to their physicochemical properties.</p><p><strong>Conclusions: </strong>While the relatively low molar activity (A_m) of the [⁶⁸Ga]Ga-NODAGA complex achieved in our setup combined with the limited amount of endogenous albumin at the infusion site (0.012-0.024 nmol) resulted in residual unbound tracer in the rat CSF in vivo, the tracers, especially the Al[¹⁸F]F-RESCA-RSA show promise for tracking CSF flow with PET, constituting the first tailored radiotracers to this end.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"38"},"PeriodicalIF":4.4,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566912","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}

{"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":"<p><strong>Background: </strong>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><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Collectively, our results suggest that [¹²⁵I]PDHQ-1, featuring a pyridinyldihydroquinolinone scaffold, shows potential as an imaging tracer for PA.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"39"},"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}