EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"eFAP-51, a novel FAPI dimer with enhanced tumor uptake and retention for theranostic applications.","authors":"Le Li, Hanyue Ma, Amber Piet, Corrina de Ridder, Debra Stuurman, Priciana Paraïso, Yann Seimbille","doi":"10.1186/s41181-026-00481-9","DOIUrl":"https://doi.org/10.1186/s41181-026-00481-9","url":null,"abstract":"<p><strong>Background: </strong>Overexpression of fibroblast activation protein (FAP) in cancer-associated fibroblasts enables a highly selective targeting strategy using FAP inhibitors. However, radiolabeled small-molecule FAP inhibitors (FAPIs) show limited tumor retention, restricting therapeutic applications. Multimerization represents a promising strategy to enhance tumor uptake and retention through polyvalent binding. Here, we report the rational design and evaluation of dimeric FAP-targeted radiopharmaceuticals for theranostic applications.</p><p><strong>Results: </strong>Based on the (4-quinolinoyl)-glycyl-2-cyanopyrrolidine (QCP) scaffold, a series of monomeric FAPIs were assembled into dimeric radioligands using three distinct tripod-based platforms and equipped with a DOTA-GA chelator for efficient radiolabeling with indium-111 and lutetium-177; systematic in vitro and in vivo evaluation of binding affinity, stability, cellular uptake, and tumor targeting identified eFAP-51 and eFAP-52 as lead candidates, both showing high radiochemical yield and purity, favorable stability, and sub-nanomolar affinity for FAP with strong selectivity over DPP4. Further studies demonstrated superior tumor targeting and pharmacokinetics for eFAP-51 compared with the clinical reference FAPI-46, with [¹¹¹In]In-eFAP-51 exhibiting more than 4-fold higher tumor uptake at 48 h post-injection (3.2 ± 0.5 vs. 0.71 ± 0.1%ID/g) and prolonged retention. eFAP-51 was subsequently radiolabeled with lutetium-177 to yield a stable therapeutic candidate, and dose-dependent studies revealed that intermediate molar doses (0.3-0.6 nmol) provided an optimal balance between tumor uptake and tumor-to-background contrast.</p><p><strong>Conclusions: </strong>The FAPI dimer eFAP-51 showed favorable tumor targeting and pharmacokinetics, supporting its potential for clinical translation in theranostic oncology.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223114","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":"Radiosynthesis and quality control testing of two ¹⁸F-labeled radiopharmaceuticals for α-synuclein imaging in clinical investigations.","authors":"Hiroki Hashimoto, Takayuki Ohkubo, Kazunori Kawamura, Tomoya Fujishiro, Daisuke Arashi, Tatsuto Sato, Takeru Seki, Masatoshi Muto, Kaito Tsukagoe, Masanao Ogawa, Yusuke Kurihara, Nobuki Nengaki, Wakana Mori, Masayuki Fujinaga, Makoto Higuchi, Ming-Rong Zhang","doi":"10.1186/s41181-026-00480-w","DOIUrl":"10.1186/s41181-026-00480-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;&lt;sup&gt;18&lt;/sup&gt;F-Labeled (E)-1-fluoro-3-((2-(4-(5-(methylamino)pyrazin-2-yl)but-1-en-3-yn-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([&lt;sup&gt;18&lt;/sup&gt;F]SPAL-T-06) and (E)-1-fluoro-3-((2-(4-(6-(methylamino)pyridine-3-yl)but-1-en-3-yn-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol ([&lt;sup&gt;18&lt;/sup&gt;F]C05-05) are positron emission tomography (PET) imaging agents for α-synuclein pathologies. Recently, we demonstrated the utility of PET imaging with [&lt;sup&gt;18&lt;/sup&gt;F]SPAL-T-06 for α-synuclein pathologies in patients with multiple system atrophy and with [&lt;sup&gt;18&lt;/sup&gt;F]C05-05 for α-synuclein pathologies in Parkinson's disease and related disorders. In this study, to establish [&lt;sup&gt;18&lt;/sup&gt;F]SPAL-T-06 and [&lt;sup&gt;18&lt;/sup&gt;F]C05-05 as PET radiopharmaceuticals for clinical investigations, we developed routine radiosynthetic procedures using an &lt;sup&gt;18&lt;/sup&gt;F-labeling synthesizer and performed quality control (QC) testing of these two PET radiopharmaceuticals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;[&lt;sup&gt;18&lt;/sup&gt;F]SPAL-T-06 and [&lt;sup&gt;18&lt;/sup&gt;F]C05-05 were synthesized by direct &lt;sup&gt;18&lt;/sup&gt;F-fluorination of their respective tetrahydropyranyl-protected tosylated precursors, followed by deprotection, using an &lt;sup&gt;18&lt;/sup&gt;F-labeling synthesizer. The non-decay-corrected radiochemical yields of [&lt;sup&gt;18&lt;/sup&gt;F]SPAL-T-06 and [&lt;sup&gt;18&lt;/sup&gt;F]C05-05 from &lt;sup&gt;18&lt;/sup&gt;F&lt;sup&gt;-&lt;/sup&gt; at the end of synthesis (EOS) were 11 ± 4.6% (n = 19) and 20 ± 6.8% (n = 37), respectively. The radiochemical purities of both PET radiopharmaceuticals exceeded 99%. The molar activities of each PET radiopharmaceutical at EOS exceeded 68 GBq/µmol, and the total synthesis times were within 100 min after irradiation. In addition, [&lt;sup&gt;18&lt;/sup&gt;F]SPAL-T-06 and [&lt;sup&gt;18&lt;/sup&gt;F]C05-05 were efficiently separated from byproducts using a semi-preparative high-performance liquid chromatography system. All QC results for the two PET radiopharmaceuticals complied with in-house QC and quality assurance specifications. The stabilities of the two PET radiopharmaceuticals were evaluated under standard fluorescent light in a general laboratory environment and under UV-cutoff light in a natural light-shielded environment. After 10 min of exposure to the standard fluorescent light, the radiochemical purity of each tracer decreased to approximately 86%. In contrast, the radiochemical purity of each tracer exceeded 99% after 60 min under UV-cutoff light in a natural light-shielded environment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;We successfully prepared two PET radiopharmaceuticals, [&lt;sup&gt;18&lt;/sup&gt;F]SPAL-T-06 and [&lt;sup&gt;18&lt;/sup&gt;F]C05-05, for clinical investigation. The radiosynthesis and QC findings provide a practical basis for establishing standardized production procedures and facilitating technology transfer to other PET centers. In particularly, all post-deprotection radiosynthesis steps and QC testing for [&lt;sup&gt;18&lt;/sup&gt;F]SPAL-T-06 and [&lt;sup&gt;18&lt;/sup&gt;F]C05-05 should be performed under UV-cutoff ","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219831","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":"Automated radiosynthesis and biodistribution of [¹⁸F]fluoroflutamide.","authors":"Gina Kaup, Jason Anthony Witek, Shelbie Jaylene Cingoranelli, Jenelle Stauff, David Raffel, Allen Frederick Brooks, Peter James Henry Scott, Jay Samuel Wright","doi":"10.1186/s41181-026-00453-z","DOIUrl":"10.1186/s41181-026-00453-z","url":null,"abstract":"<p><strong>Background: </strong>The androgen receptor (AR) is upregulated in multiple cancers, such as salivary gland cancer, glioblastoma, triple-negative breast cancer, and, most commonly, prostate cancer. Imaging expression of the AR using a radiolabeled AR antagonist would enable non-invasive clinical staging and assessment of tumor heterogeneity via positron emission tomography (PET), complementing the findings of a [⁶⁸Ga]PSMA-11 scan. Previous efforts described the radiolabeling of enzalutamide with fluorine-18 but were limited by low molar activity. In this study, we showcase an efficient, reproducible automated synthesis of [¹⁸F]fluoroflutamide via zinc-mediated radiofluorination and assess its biodistribution in preclinical models of prostate cancer.</p><p><strong>Results: </strong>From 1.87 Ci (69.19 GBq) of [¹⁸F]fluoride, [¹⁸F]fluoroflutamide was isolated with a non-decay-corrected radiochemical yield of 3.46 ± 1.30% (n = 4) and a radiochemical purity of > 99% in an average 79 min from end-of-beam using a bromoamide precursor. The average A_m was 1.57 Ci/µmol (or 58.23 GBq/µmol) at the end of synthesis, and the radiochemical purity after 4 h was > 97%, indicating negligible radiolysis. A biodistribution and imaging study was performed using nude athymic mice with 22Rv1 human prostate cancer xenografts. From the results of this study, we observed a 'mass effect' in which carrier-added mice displayed an increased uptake of the tracer across most organs.</p><p><strong>Conclusions: </strong>Herein, we report the optimized automated radiosynthesis of [¹⁸F]fluoroflutamide with high purity and sufficient yield for preclinical evaluation of AR-targeted imaging in mouse models of prostate cancer. The lack of uptake in androgen receptor-rich tissues and xenografts suggests impaired in vivo target engagement. While α-tertiary fluorination may attenuate CYP1A2-mediated oxidation to the higher-affinity 2-hydroxyflutamide metabolite, the observed signal is also consistent with reduced intrinsic AR affinity and/or altered pharmacokinetics of the fluorinated analog.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219847","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":"Assessment of PET drug adverse events in the U.S. since the implementation of 21 CFR part 212.","authors":"Marianna Dakanali, Henry F VanBrocklin, Steven S Zigler, Peter J H Scott","doi":"10.1186/s41181-026-00482-8","DOIUrl":"https://doi.org/10.1186/s41181-026-00482-8","url":null,"abstract":"<p><strong>Background: </strong>Multiple new Positron Emission Tomography (PET) radiopharmaceuticals (RPhs) have recently been approved by the U.S. Food and Drug Administration (FDA). Despite the generally accepted safety profile of PET RPhs supported by millions of doses administered per year, the microdoses used in most injections, and the low incidence of adverse events (AEs), there appear to be elevated concerns from regulatory authorities regarding the safety of PET RPhs in recent years. There have been prior reports on the prevalence of AEs from RPhs, but most of them are outdated and do not reflect the current state-of-the-art and best practices. To address the gap, this retrospective study assesses risks associated with PET RPhs by reviewing AEs reported to the FDA Adverse Events Reporting System (FAERS) since the implementation of the PET good manufacturing practice (GMP) regulations in 21 CFR 212 in 2012. Data for AEs reported for approved PET RPhs were collected from the FAERS database. Data were collected during December 2025 for AEs reported between 2012 and 2024. FDA approved PET RPhs were searched using all known names for each drug. For each RPh, the following tables were downloaded from the database: (a) case count by received year; (b) cases by reaction; and (c) listing of cases. Tables downloaded for each radiopharmaceutical were combined, and duplicated entries removed. AE reports were then categorized based on the manufacturing regulatory oversight and, for the purposes of this report, we focused on AEs reported for 10 PET RPhs manufactured under 21 CFR 212.</p><p><strong>Results: </strong>Almost 24 million adverse event reports for all drug products were transmitted to FDA between 2012 and 2024. Of these, 932 (or 0.0039%) were AEs submitted to FAERS for FDA-approved PET RPhs manufactured in the US. Of these AEs, 451 were reported for PET RPhs manufactured under 21 CFR 212. This represents approximately 7.0 AEs per 10⁵ RPh injections performed in 2024 for all PET RPhs or 4.3/10⁵ for PET RPhs manufactured under the PET GMP regulations. At least one adverse reaction to the RPh was reported in 237 of the 451 cases recorded, and two-thirds of these (157, 66.2%) were characterized as non-serious.</p><p><strong>Conclusions: </strong>The FAERS data confirm that PET RPhs can be generally recognized as safe and effective. The extremely low numbers of AEs for PET RPhs manufactured according to 21 CFR 212 and the lack of correlation between manufacturing issues and safety AEs overall support a low risk profile for this class of drugs. Moreover, these data do not appear to justify significant changes to the existing regulations, or more stringent regulation of PET drug manufacture beyond those currently in place.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223122","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":"Inline gamma spectroscopy and liquid scintillation HPLC reveal daughters in 225Ac-radiopharmaceutical","authors":"Guilhem Claude,&nbsp;Matthias Balzer,&nbsp;Winfried Brenner,&nbsp;Frank Bruchertseifer,&nbsp;Alfred Morgenstern,&nbsp;David Thonon,&nbsp;Sarah Spreckelmeyer","doi":"10.1186/s41181-026-00476-6","DOIUrl":"10.1186/s41181-026-00476-6","url":null,"abstract":"<div><h3>Background</h3><p>Analytical data for ²²⁵Ac-labeled radiopharmaceuticals are currently obtained using thin-layer chromatography and high-performance liquid chromatography, the latter followed by offline fraction collection and delayed gamma-counting after secular equilibrium with gamma-emitting daughters has been reached. These procedures are slow and do not depict the distribution of daughter radionuclides. An inline HPLC detection setup combining liquid scintillation detection and LaBr₃-based gamma-spectroscopy is presented to enable faster and more informative analysis of a ²²⁵Ac radiopharmaceutical.</p><h3>Results</h3><p>Four chromatographic signals were identified corresponding to uncomplexed ²²¹Fr with at most a minor contribution of free ²¹³Bi, [²¹³Bi]Bi-PSMA I&amp;T, [²²⁵Ac]Ac-PSMA I&amp;T, and [²⁰⁹Pb]Pb-PSMA I&amp;T. The retention times corresponded to those of the non-radioactive analogs determined by UV detection. Assignments were confirmed by fraction collection followed by gamma-spectroscopy and beta liquid scintillation counting. The distribution of these species changed upon heating the reaction mixture or after addition of another ligand.</p><h3>Conclusions</h3><p>The combined detection setup enables rapid observation of isotope distribution and daughter behavior during chromatographic analysis and avoids fraction handling by operating as a closed system, thereby reducing contamination risk and radiation exposure. This approach may contribute to improved quality control procedures for ²²⁵Ac radiopharmaceuticals and other alpha-emitting radionuclides. At the present stage, however, it should be regarded as a qualitative to semi-quantitative proof-of-principle.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547587","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":"Synthesis and in vitro evaluation of pharmacokinetically optimized 99mTc-labeled cholecystokinin-2 receptor-targeted peptides for improved SPECT imaging","authors":"Veronika Felber,&nbsp;Nadine Holzleitner,&nbsp;Thomas Günther","doi":"10.1186/s41181-026-00477-5","DOIUrl":"10.1186/s41181-026-00477-5","url":null,"abstract":"<div><h3>Background</h3><p>Hitherto, clinically applied ^99mTc-based cholecystokinin-2 receptor (CCK-2R) ligands suffer from limited in vivo stability. Therefore, we focused on the development of pharmacokinetically optimized ^99mTc-labeled CCK-2R ligands for improved imaging of CCK-2R-overexpressing malignancies via single-photon emission computed tomography (SPECT). The novel CCK-2R ligands were designed based on the recently published compounds CCK-66, rhCCK-18 and rhCCK-84.</p><h3>Results</h3><p>CCK-2R ligands were prepared by solid-phase peptide synthesis (SPPS) and ^99mTc-labeled via the tetraamine (N₄) chelator (95 °C, 15 min) with final radiochemical purities ≥ 95% (radiochemical yields &gt; 99%, n = 39), as determined by radio-RP-HPLC. Affinity (IC_50,inverse) and internalization experiments were performed using CCK-2R⁺ AR42J cells. Lipophilicity (logD_7.4), human serum albumin (HSA) binding and stability in human serum (4 h, 37 °C) was determined as well. Four of the seven novel CCK-2R ligands, i.e. [^99mTc]Tc-N₄-CCK-66 and [^99mTc]Tc-N₄-CCK-103 to -105, exhibited similar CCK-2R affinities compared to the reference ligands [¹⁷⁷Lu]Lu-DOTA-PP-F11N and [¹⁷⁷Lu]Lu-DOTA-CCK-66 (IC_50,inverse: 28.2–40.3 nM). [^99mTc]Tc-N₄-CCK-66 and [^99mTc]Tc-N₄-CCK-104 demonstrated high CCK-2R-mediated internalization (223.8 ± 0.1% and 145.2 ± 0.1% compared to [¹⁷⁷Lu]Lu-DOTA-PP-F11N, respectively), high stability in human serum (&gt; 95%) and similar lipophilicity (log<i>D</i>_7.4: − 2.09 to − 2.42) and HSA binding (47.5–53.2%) compared with [¹⁷⁷Lu]Lu-DOTA-CCK-66. 4-(Di-<i>tert</i>-butyl(hydroxy)silyl)benzoic acid (SiOH-BA)-bearing compounds [^99mTc]Tc-N₄-CCK-100 and [^99mTc]Tc-N₄-CCK-103 showed an elevated lipophilicity (logD_7.4: − 1.89 to − 0.95) and HSA binding (78.1–89.1%) as well as a reduced stability in human serum (87.0–93.0%), but higher internalization than [¹⁷⁷Lu]Lu-DOTA-PP-F11N (145.0 ± 0.1% and 219.5 ± 0.1%, respectively).</p><h3>Conclusions</h3><p>Several ^99mTc-labeled CCK-2R ligands with very favorable in vitro characteristics were successfully developed in this study. In particular, [^99mTc]Tc-N₄-CCK-66 and [^99mTc]Tc-N₄-CCK-104 are highly recommended for further evaluation in in vivo studies to examine their potential as ^99mTc-based SPECT agents for improved imaging of CCK-2R-expressing malignancies. Furthermore, a possible radiotheranostic use of these N₄-conjugated compounds could be explored in future studies using ^186/188Re.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534951","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":"Optimization of [18F]FBPA production for clinical translation through precursor development and manufacturing route evaluation","authors":"Ting-Yu Chang,&nbsp;Yu-Hou Yu,&nbsp;Zhen-Fan You,&nbsp;Ping-Chuan Cho,&nbsp;Yuh-Feng Wang,&nbsp;Chun-Yi Wu","doi":"10.1186/s41181-026-00471-x","DOIUrl":"10.1186/s41181-026-00471-x","url":null,"abstract":"<div><h3>Background</h3><p>4-Borono-2-[¹⁸F]fluorophenylalanine ([¹⁸F]FBPA) is an important imaging agent for identifying suitable candidates for boron neutron capture therapy (BNCT). This study aimed to develop three new precursors for the no-carrier-added synthesis of [¹⁸F]FBPA and to establish corresponding automated radiosynthesis protocols suitable for routine production.</p><h3>Results</h3><p>Following manual optimization, the optimized conditions were successfully translated to automated synthesis, resulting in non-decay-corrected radiochemical yields of 2.6% ± 1.3% for the BNBA-based protocol, 0.3% ± 0.1% for the P-02-based protocol, and 3.1% ± 0.0% for the P-03-based protocol, respectively. MicroPET/MR imaging and biodistribution analyses demonstrated the highest tumor uptake for [¹⁸F]FBPA-sorbitol conjugate ([¹⁸F]FBPA-Sor), followed by [¹⁸F]FBPA and [¹⁸F]FBPA-fructose conjugate ([¹⁸F]FBPA-Fr). Tumor standardized uptake values obtained from microPET/MR imaging were 1.72 ± 0.25 for [¹⁸F]FBPA, 1.29 ± 0.25 for [¹⁸F]FBPA-Fr, and 2.57 ± 0.28 for [¹⁸F]FBPA-Sor, with corresponding tumor-to-muscle (T/M) ratios of 3.34 ± 1.07, 4.64 ± 0.60, and 9.38 ± 0.88, respectively. Biodistribution studies further confirmed enhanced tumor accumulation of [¹⁸F]FBPA-Sor, with tumor uptake values of 10.46 ± 0.61, 11.51 ± 2.75, and 19.32 ± 1.57%ID/g for [¹⁸F]FBPA, [¹⁸F]FBPA-Fr, and [¹⁸F]FBPA-Sor, respectively. In addition, [¹⁸F]FBPA-Sor demonstrated the highest tumor-to-muscle and tumor-to-blood ratios, indicating that alditol conjugation significantly influences tracer pharmacokinetics and biodistribution profiles.</p><h3>Conclusions</h3><p>These findings provide practical insights into precursor design, radiosynthesis optimization, and imaging performance, offering a rational framework to guide future development and clinical translation of [¹⁸F]FBPA as a companion diagnostic for BNCT.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00471-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337343","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":"Synthesis and in vivo evaluation of a bifunctional, glutamic acid derived chelator for the 203/212Pb theranostic pair","authors":"Jarred Michael Scaffidi-Muta,&nbsp;Kwong Ching Li,&nbsp;Didier Boucher,&nbsp;Thomas Kryza,&nbsp;William Tieu,&nbsp;Andrew David Abell","doi":"10.1186/s41181-026-00473-9","DOIUrl":"10.1186/s41181-026-00473-9","url":null,"abstract":"<div><h3>Background</h3><p>The biodistributions of radiometalated peptides and small molecules are greatly influenced by the charge conferred by the metal-chelator complex. Careful fine-tuning of this charge thus represents an attractive method to optimise pharmacokinetic properties. For this to be an effective strategy, numerous suitable chelators must be available for a given radiometal; each possessing a different net charge. Herein we report the synthesis of 2-(4,7,10-tris(2-amino-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)pentanedioic acid (DOTAMGA), a bifunctional chelator for the ^203/212Pb theranostic pair containing a single negative charge, previously unattainable with reported radiolead chelators. DOTAMGA was incorporated into a radiopharmaceutical targeting the melanocortin 1 receptor (MC1R), a receptor highly expressed by melanomas, and evaluated in vivo against the commonly used radiolead chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic amide (TCMC).</p><h3>Results</h3><p>DOTAMGA was synthesised and conjugated to the MC1R targeting peptide MC1RL for subsequent investigation alongside TCMC-MC1RL. DOTAMGA-MC1RL and TCMC-MC1RL exhibited comparable affinity for MC1R in a series of competition binding assays with MC1R expressing cells. DOTAMGA-MC1RL was effectively labelled with ²¹²Pb and ²⁰³Pb under standard radiolabelling conditions, and UV–Vis experiments demonstrated more rapid Pb²⁺ complexation than TCMC-MC1RL. Both ²¹²Pb-labelled compounds remained &gt; 90% intact after 24 h incubation in human serum. In B16F0 melanoma bearing C57BL/6 mice, DOTAMGA-MC1RL exhibited reduced hepatic uptake compared to TCMC-MC1RL, though a reduction in tumour uptake and resulting tumour to organ uptake ratios were also observed.</p><h3>Conclusions</h3><p>DOTAMGA represents a promising tool to optimise the pharmacokinetic properties of ^203/212Pb radiopharmaceuticals, and is a useful addition to existing radiolead chelators on account of its unique charge.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387167","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 assessment of target-binding fractions in molecular imaging agents using size-exclusion HPLC","authors":"Ashtyn McAdoo,&nbsp;Kamal Jouad,&nbsp;Eben L. Rosenthal,&nbsp;Adam J. Rosenberg","doi":"10.1186/s41181-026-00469-5","DOIUrl":"10.1186/s41181-026-00469-5","url":null,"abstract":"<div><h3>Background</h3><p>The clinical translation of molecularly targeted therapeutics and imaging agents represents a cornerstone of precision oncology, with the global theranostics market projected to exceed $25 billion by 2030. However, the development of theragnostic agents or diagnostic companions remains constrained by analytical bottlenecks in quality control, such as target-binding fraction, which are increasingly required by regulatory agencies as product release criteria during the translation process. Current methods, including enzyme-linked immunosorbent assay (ELISA), which require specialized resources or external CROs, or bead-based assays for radiolabeled compounds, which involve complex multi-step protocols; these limitations and others hamper their practical implementation in clinical manufacturing environments. Assay delays can postpone clinical trial initiation, increase development costs, and delay patient access to these agents.</p><h3>Results</h3><p>We have developed and validated a rapid, size-exclusion high-performance liquid chromatography (SE-HPLC) method for the determination of target-binding fractions of labeled biologics. The method separates the unbound biologic from the larger antigen-bound complex, allowing for rapid quantification. We validated the method using a panel of fluorescently labeled antibodies (panitumumab-IRDye800CW, nivolumab-IRDye800CW) and radiolabeled biologics ([18F]GEH200521, [18F]NOTA-ABY-030), assessing linearity, specificity, and concentration independence. The SE-HPLC method achieved excellent separation of bound and unbound species with a resolution (Rs) of 3.2. A strong linear relationship (R² = 0.999) was observed between the antigen-to-antibody ratio and the measured binding fraction. The method demonstrated high specificity, with no binding detected with non-target antigens. The total assay and analysis time was less than 35 min, a significant improvement over traditional methods.</p><h3>Conclusions</h3><p>SE-HPLC provides a rapid, specific, and cost-effective alternative to traditional binding fraction assessment methods, reducing quality control timelines from weeks/hours to minutes. The method’s compatibility with both fluorescent and radiolabeled biologics and integration with existing HPLC infrastructure represents a significant advancement in development workflows.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387174","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":"High-yield, standardised automated radiosynthesis process for routine clinical insulinoma PET with [⁶⁸Ga]Ga-NODAGA-exendin-4","authors":"Elodie Duray,&nbsp;Matthieu Sacrez,&nbsp;Marine Hawotte,&nbsp;Charlotte Collet,&nbsp;Christian Vanasschen,&nbsp;Nicolas Veran,&nbsp;Corentin Warnier","doi":"10.1186/s41181-026-00470-y","DOIUrl":"10.1186/s41181-026-00470-y","url":null,"abstract":"<div><h3>Background</h3><p>Insulinoma is a rare pancreatic neuroendocrine tumour characterised by inappropriate insulin secretion and recurrent hypoglycaemia. Owing to their small size and intrapancreatic localisation, insulinomas are frequently difficult to detect using conventional anatomical imaging techniques. Functional imaging based on positron emission tomography has therefore gained increasing interest, particularly through targeting of the glucagon-like peptide-1 receptor, which is highly overexpressed in most insulinomas. Among available tracers, gallium-68-labelled NODAGA-exendin-4 has demonstrated excellent diagnostic performance. However, its routine clinical implementation remains limited by the absence of a harmonised, robust and transferable radiosynthesis protocol compatible with hospital radiopharmacy practice. The aim of this work was to optimise and harmonise the automated preparation of gallium-68-labelled NODAGA-exendin-4 by systematically evaluating critical synthesis parameters and validating the optimised process across multiple commercially available gallium-68 generators. Using an automated synthesis module, key variables including precursor amount, labelling temperature and duration, formulation additives, workflow sequence and quality control conditions were investigated. The optimised protocol was subsequently validated using generators from three different manufacturers.</p><h3>Results</h3><p>Optimisation studies demonstrated that formulation-related parameters, particularly the post-labelling addition of polysorbate 20, resulted in improved radiochemical conversion and reduced residual activity within the synthesis cassette. An optimal precursor amount of 20 µg was identified as a compromise between radiochemical yield and clinical injectability constraints. Radiolabelling at 95 °C for 12 min ensured high conversion while reducing overall synthesis time. Validation runs showed excellent reproducibility, with non-decay-corrected yields ranging from 60 to 73% and decay-corrected yields reaching up to 93%, independent of generator type. Radiochemical purity consistently exceeded 95%, and all quality control parameters complied with established specifications.</p><h3>Conclusions</h3><p>This study establishes a simplified, efficient and generator-independent automated synthesis of gallium-68-labelled NODAGA-exendin-4. By addressing key translational and regulatory constraints, the proposed protocol provides a practical foundation for the routine clinical implementation of glucagon-like peptide-1 receptor imaging in patients with suspected insulinoma.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00470-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358893","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}