EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Development of NOTA-based antibody-fragment labeling agent that reduces early renal radioactivity levels","authors":"Shunsuke Katamoto,&nbsp;Hiroyuki Suzuki,&nbsp;Madoka Kobayashi,&nbsp;Shota Kise,&nbsp;Kento Kannaka,&nbsp;Nobuki Kazuta,&nbsp;Tomoya Uehara","doi":"10.1186/s41181-026-00460-0","DOIUrl":"10.1186/s41181-026-00460-0","url":null,"abstract":"<div><h3>Background</h3><p>Gallium-68 (⁶⁸Ga) and copper-64 (⁶⁴Cu) are radiometals used for nuclear medicine imaging and therapy. The compound 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) forms stable complexes with these radiometals. However, ⁶⁸Ga/⁶⁴Cu-labeled-low molecular weight proteins show high radioactivity levels in the kidneys. To address this problem, a NOTA-conjugated Met-Val-Lys (MVK)-maleimide (Mal) (NOTA-MVK-Mal), was recently designed to reduce renal radioactivity levels. The agent achieved this by releasing radiometal-NOTA-methionine as a radiometabolite via the action of renal brush border enzymes. As ⁶⁸Ga and ⁶⁴Cu have short half-lives, it is crucial to reduce renal radioactivity from the early post-injection-period. Based on this molecular strategy, this study designed and synthesized a new NOTA-based radiometal-labeling agent, designated NOTA-conjugated Phe-Gly-Lys (FGK)-Mal (NOTA-FGK-Mal), which reduced renal radioactivity in the earlier post-injection period.</p><h3>Results</h3><p>Considering that the FGK sequence is a substrate of enzymes on the renal brush border, isothiocyanatobenzyl-NOTA was conjugated to an antibody Fab fragment through a FGK linkage to produce [⁶⁷Ga]Ga-NOTA-FGK-Fab. Enzymatic recognition of the linkage was evaluated using a low-molecular-weight [⁶⁷Ga]Ga-NOTA-FGK derivative. The biodistribution of radioactivity after the injection of [⁶⁷Ga]Ga-NOTA-FGK-Fab into mice was compared with that of [⁶⁷Ga]Ga-NOTA-MVK-Fab. The FGK linkage was recognized by brush border membrane enzymes to liberate [⁶⁷Ga]Ga-NOTA-Phe-Gly. This indicated that the recognition of the FGK sequence in the [⁶⁷Ga]Ga-NOTA-FGK derivative was the GK sequence, not the expected FG sequence. When injected into mice, [⁶⁷Ga]Ga-NOTA-FGK-Fab resulted in lower renal radioactivity levels than those induced by [⁶⁷Ga]Ga-NOTA-MVK-Fab without a reduction in tumor radioactivity levels.</p><h3>Conclusion</h3><p>These results suggest that NOTA-FGK(Mal) is a useful radiometal labeling agent for low-molecular-weight proteins that reduces renal radioactivity levels from as early as post-injection. This molecular design is not dependent on the type of antibody or its constructs, it is expected that NOTA-FGK(Mal) will also be applicable to a variety of target molecules.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00460-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196802","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":"Design and development of a semi-automated solid target assembly for the indigenous production of medical radioisotopes in the PETrace-800 cyclotron","authors":"Kanchan Kushwaha,&nbsp;Kavindra Pathak,&nbsp;Tejinder P. Sabharwal,&nbsp;Sunil Kamble,&nbsp;Arpit Mitra,&nbsp;Sudeep Sahu,&nbsp;Pravind Maletha,&nbsp;Nand Kishore Prasad,&nbsp;Manish Kumar,&nbsp;Sharmila Banerjee","doi":"10.1186/s41181-026-00448-w","DOIUrl":"10.1186/s41181-026-00448-w","url":null,"abstract":"<div><h3>Background</h3><p>Molecular imaging enables the non-invasive visualization of physiological processes at the cellular and molecular levels and is central to diagnostic nuclear medicine. Among clinically important theranostic radionuclides, ⁶⁴Cu and ¹¹¹In are of particular interest due to their favourable decay characteristics and applications in radiopharmaceutical development. Their cyclotron production via the ⁶⁴Ni(p,n)⁶⁴Cu and ¹¹¹Cd(p,n)¹¹¹In reactions generally require irradiation of enriched solid targets to achieve adequate yields. Although liquid target approaches have been explored, solid targets remain preferable for radiometal production due to higher yields and more efficient utilization of enriched target material.</p><h3>Results</h3><p>To enhance the capability of the two-decade old commercial medical cyclotron (PETtrace 800) at the Radiation Medicine Centre (RMC), originally configured only for liquid and gaseous targets, an indigenously designed and fabricated solid target irradiation assembly was developed and integrated into the Medical Cyclotron Facility (MCF). This work demonstrates the successful routine production of pharmaceutical-grade ⁶⁴Cu and ¹¹¹In, achieving yields of 74 MBq µA^{− 1} h^{− 1} and 4.88 MBq µA^{− 1} h^{− 1}, respectively.</p><h3>Conclusion</h3><p>This development significantly broadens the functional scope of the existing cyclotron infrastructure and establishes a dependable local production pathway for clinically important theranostic radionuclides.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154828","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":"Quality and pratical determinants in [99mTc]Tc-tetrofosmin preparation: hygrometry, syringe sorption & maximal activity per kit","authors":"Quentin Buon,&nbsp;Hugo Tep,&nbsp;Eli Bassi,&nbsp;Pr Alessio Imperiale,&nbsp;Anne Dory,&nbsp;Bénédicte Gourieux,&nbsp;Alice Ressault","doi":"10.1186/s41181-026-00454-y","DOIUrl":"10.1186/s41181-026-00454-y","url":null,"abstract":"<div><h3>Background</h3><p>Tetrofosmin, labelled with technetium-99m ([^99mTc]Tc-tetrofosmin), is a widely used radiopharmaceutical for myocardial perfusion imaging. Despite its routine use, several practical aspects of its preparation remain insufficiently characterized. This study addressed three operational issues: (i) the potential impact of environmental hygrometry on radiochemical purity assessment using ITLC-SA, as current guidelines provide no recommendations for humidity during quality control; (ii) the extent of sorption in medical syringes, comparing two-part and lubricated three-part syringes due to the lipophilic nature of tetrofosmin; and (iii) the radiochemical conformity of preparations performed with activities exceeding the 12-GBq limit stated in the manufacturer’s instructions.</p><h3>Results</h3><p>Hygrometry &gt; 60% brings 99.7% nonconformities with ITLC-SA test strip of the [^99mTc]Tc-tetrofosmin quality control. Measures show significant superiority of 3P syringe mean sorptions over 2P syringes, with successive rinses and two different infusion time points. However, all measured sorption was under 10%, considered as clinically acceptable. Median activity was 17.31 GBq over a 1-year period, while the product instructions allow for a maximum 12 GBq per kit. All quality controls were conforms, demonstrating possibility to overcharge kits and improve maximal activity.</p><h3>Conclusion</h3><p>Hygrometry is clearly a major parameter and should be not only monitored but controlled like pressure or temperature. There is a significant superiority about [^99mTc]Tc-tetrofosmin sorption in 3P syringes compared to 2P syringes. However, less than 10% sorption difference cannot be considered as clinically significant. 3P syringes are probably not as problematic as it seems for [^99mTc]Tc-tetrofosmin preparations. The increase of maximal activity per tetrofosmin kit doesn’t shows nonconformities about [^99mTc]Tc-tetrofosmin preaparation and conserve safety of use for professionals and patients.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148147843","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":"Scaling the production of bromine-76 and bromine-77 labeled poly-ADP-ribose-polymerase-targeted theranostics for preclinical use","authors":"Taylor R. Johnson,&nbsp;Hong Beom Lee,&nbsp;Yngve Guttormsen,&nbsp;Jason C. Mixdorf,&nbsp;Todd E. Barnhart,&nbsp;Jonathan W. Engle,&nbsp;Paul A. Ellison","doi":"10.1186/s41181-026-00458-8","DOIUrl":"10.1186/s41181-026-00458-8","url":null,"abstract":"<div><h3>Background</h3><p>Bromine-76, a positron emitting radionuclide for positron emission tomography (PET) imaging, and bromine-77, an Auger electron (Ae) emitting radionuclide, make a unique halogen theranostic pair. These isotopes have previously been used to synthesize a rucaparib-derived, poly-ADP-ribose polymerase inhibitor ([^76/77Br]RD1). As [⁷⁷Br]bromide activity in [^76/77Br]RD1 radiosyntheses increased, coincident with solid target hardware changes in our facility, radiopharmaceutical yield became less reproducible. This work describes the modifications to this hardware, distillation procedures, and [^76/77Br]bromide solution chemistry to enable reproducible production of preclinical quantities of [^76/77Br]RD1.</p><h3>Results</h3><p>Isotopically enriched cobalt selenide targets had production yields of 50.7 ± 8.7 MBq/µAh for bromine-76 and 14.5 ± 3.3 MBq/µAh for bromine-77, consistent with previous reports. Adoption of the GE PETtrace Solid Target Platform (STP) increased target backing diameter to 22 mm. Increasing dry distillation duration from 5 to 6 min to 8–9 min and furnace temperature from 1050 to 1055 °C released 94 ± 5% (<i>n</i> = 17) of activity, in agreement with previous smaller targets (92 ± 13%, <i>n</i> = 35). Rinsing glassware and loading the quaternary methyl ammonium (QMA) anion exchange cartridge in 1 mM sodium bicarbonate reduced [^76/77Br]bromide elution volume from 2.9 to 0.9 mL. Across all distillations, when [⁷⁷Br]bromide was isolated in less than 1 mL of QMA eluant, copper-mediated bromodeborylation of a BPin precursor molecule formed [^76/77Br]RD1 with a radiochemical conversion of 98 ± 3% (<i>n</i> = 17) and overall radiopharmaceutical yield of 70 ± 10% (<i>n</i> = 15) following purification and final formulation. Up to 580 MBq of purified [⁷⁷Br]RD1 have been produced with this system.</p><h3>Conclusion</h3><p>The new target production technique made targets suitable for long-term use with the GE PETtrace STP. Following modifications to the distillation process, [^76/77Br]bromide production yields from GE PETtrace STP targets agreed with those previously published. The changes described in this work not only aimed to maximize [^76/77Br]bromide recovery after distillation, but also chemical reactivity in large-scale [^76/77Br]RD1 radiopharmaceutical syntheses. This balancing act resulted in a slightly lower [^76/77Br]bromide recovery yield but more consistently [^76/77Br]RD1 product yield.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136311","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 an automated radiosynthesis for [68Ga]Ga-NODAGA[40Lys]-Exendin-4 in sodium acetate buffer","authors":"Maïlys Ragot,&nbsp;Pauline Reynaud-Orhon,&nbsp;Alban Revy,&nbsp;Marie Batisse-Lignier,&nbsp;Valentin Brusseau,&nbsp;Antony Kelly,&nbsp;Hosameldin Otman,&nbsp;Florent Cachin,&nbsp;Marion Chanchou,&nbsp;Sophie Levesque,&nbsp;Marion Tempier","doi":"10.1186/s41181-026-00452-0","DOIUrl":"10.1186/s41181-026-00452-0","url":null,"abstract":"<div><h3>Background</h3><p>[⁶⁸Ga]Ga-NODAGA[40Lys]-Exendin-4 (⁶⁸Ga-Ex-4) is a new PET radiopharmaceutical targeting GLP-1-R that showed great specificity and sensitivity in the topographic diagnosis of benign insulinoma. We herein report the development of a new method for ⁶⁸Ga-Ex-4 radiolabeling in sodium acetate buffer, automated on the miniAllinOne synthesizer.</p><h3>Results</h3><p>Key parameters were reaction volume, due to low amount of peptide, and pH. At a reaction volume of 2.65 mL and pH 2.9, the reaction yielded 80% of ⁶⁸Ga-Ex-4. The use of polysorbate and cooling of the solution allows to decrease the adsorption on the reaction vial (from 29 to 2% of total activity remaining on the vial). ⁶⁸Ga-Ex-4 is purified on a HLB cartridge. Final product was obtained within 40 min, with a mean radiochemical purity of 97% and a radiochemical yield of 67%.</p><h3>Conclusions</h3><p>We have successfully developed a new radiolabeling method for [⁶⁸Ga]Ga-NODAGA-[40Lys]Exendin-4, automated on a miniAllinOne synthesizer and using sodium acetate buffer, suitable for clinical application.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136385","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":"CXCR4-targeted PET imaging of glioblastoma using [68Ga]Ga-TD-01: from pharmacokinetics and dosimetry to theranostic potential","authors":"Piyapan Suwattananuruk,&nbsp;Stine Figenschau,&nbsp;Angel Moldes-Anaya,&nbsp;Efat Muhammad Arshad,&nbsp;Rodrigo Berzaghi,&nbsp;Lars Kjelsberg Pedersen,&nbsp;Rune Sundset,&nbsp;Pornchai Rojsitthisak,&nbsp;Opa Vajragupta,&nbsp;Mathias Kranz","doi":"10.1186/s41181-026-00457-9","DOIUrl":"10.1186/s41181-026-00457-9","url":null,"abstract":"<div><h3>Background</h3><p>Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis and limited treatment options. Chemokine receptor type 4 (CXCR4) plays a key role in GBM invasion and therapy resistance, making it an attractive target for molecular imaging and theranostics. We developed [⁶⁸Ga]Ga-TD-01, a next-generation positron emission tomography (PET) radiotracer for CXCR4 imaging, and evaluated its pharmacokinetics, dosimetry, and translational potential.</p><h3>Results</h3><p>In mice bearing orthotopic GL261 GBM, dynamic PET/MRI, receptor blocking studies, and kinetic modeling demonstrated a specific binding component and high tumor-to-background contrast. [⁶⁸Ga]Ga-TD-01 showed high tumor uptake (5.4 ± 4.3%ID/g at 9 min), low uptake in normal brain (2.2 ± 1.7%ID/g), and a tumor-to-background ratio of 2.9 ± 0.2 at 60 min, which was significantly reduced by CXCR4 blockade. PET pharmacokinetic modeling confirmed increased tumor retention (Vt of 0.5 ± 0.07 ml/cm³ for tumor; Vt of 0.2 ± 0.05 ml/cm³ for brain). The radiotracer exhibited high in vivo stability, rapid renal clearance, and favorable biodistribution. CXCR4 expression was confirmed in both murine and human GBM tissues by RNAscope. Human dosimetry extrapolation estimated an effective dose of 4.6 mSv for a standard PET scan, comparable to approved tracers.</p><h3>Conclusions</h3><p>When compared with reported data for [⁶⁸Ga]Ga-Pentixafor, [⁶⁸Ga]Ga-TD-01 showed tumor uptake within the reported range and low background accumulation; however, no direct head-to-head comparison was performed. These results support [⁶⁸Ga]Ga-TD-01 as a promising CXCR4-targeted imaging agent and a candidate for further theranostic development.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00457-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979975","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":"Radiochemistry and comparative in vitro assessment of PSMA-617 labeled with lead-212 (212Pb), actinium-225 (225Ac), and lutetium-177 (177Lu)","authors":"Abhijit Bera,&nbsp;Graham Ragland,&nbsp;Yuhan Zhang,&nbsp;Patricia G. Madel,&nbsp;Jasmine B’Lanton,&nbsp;Atchimnaidu Siriki,&nbsp;Chin-Tu Chen,&nbsp;Russell Z. Szmulewitz,&nbsp;Satish K. Chitneni","doi":"10.1186/s41181-026-00456-w","DOIUrl":"10.1186/s41181-026-00456-w","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;PSMA-targeted radioligand therapy is a promising approach for the treatment of advanced prostate cancer; however, the clinical efficacy of [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617 (Pluvicto&lt;sup&gt;®&lt;/sup&gt;) is limited by the relatively low cytotoxic potency of the β-emitting radionuclide &lt;sup&gt;177&lt;/sup&gt;Lu (t&lt;sub&gt;1/2&lt;/sub&gt;: 6.65 d). This has driven high interest in α-emitting radionuclides, such as &lt;sup&gt;212&lt;/sup&gt;Pb (t&lt;sub&gt;1/2&lt;/sub&gt;: 10.64 h) and &lt;sup&gt;225&lt;/sup&gt;Ac (t&lt;sub&gt;1/2&lt;/sub&gt;: 9.92 d), which deliver high Linear Energy Transfer (LET) and cause more potent tumor cell killing. In this work, we assessed the radiolabeling and in vitro characteristics of &lt;sup&gt;212&lt;/sup&gt;Pb- and &lt;sup&gt;225&lt;/sup&gt;Ac-labeled PSMA-617 compared with [&lt;sup&gt;177&lt;/sup&gt;Lu]LuPSMA-617, using two different PSMA-positive prostate cancer cell lines, LNCaP-AR and DU145-PSMA, along with paired negative controls.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The radioligands were synthesized with an isolated radiochemical yield of &gt; 95% for [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617 and about 45% for [&lt;sup&gt;212&lt;/sup&gt;Pb]Pb-PSMA-617 and [&lt;sup&gt;225&lt;/sup&gt;Ac]Ac-PSMA-617. The molar activity after Sep-Pak purification was about 37.0 MBq/nmol for [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617, 4.4–11.1 MBq/nmol for [&lt;sup&gt;212&lt;/sup&gt;Pb]Pb-PSMA-617, and 0.22–0.55 MBq/nmol for [&lt;sup&gt;225&lt;/sup&gt;Ac]Ac-PSMA-617. In vitro stability studies in PBS, human serum, and whole blood revealed ≥ 90% stability for [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617 (up to 5 days) and [&lt;sup&gt;212&lt;/sup&gt;Pb]Pb-PSMA-617 (24 h), whereas [&lt;sup&gt;225&lt;/sup&gt;Ac]Ac-PSMA-617 exhibited ~ 72% stability in PBS, &gt; 94% in serum, and &gt; 86% in whole blood for 5 days. The uptake of [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617 in LNCaP-AR cells was 7.5 ± 0.6%, with about 33% of the cell-bound activity internalized at 4 h. The uptake and internalization were significantly higher in the PSMA-overexpressing cell line DU145-PSMA (31.1 ± 0.6%, 65% internalized). Compared to [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617, [&lt;sup&gt;212&lt;/sup&gt;Pb]Pb-PSMA-617 showed about 2-fold higher uptake and increased internalization in LNCaP-AR cells at 4 h (14.2 ± 0.0%, 47.1% internalized), but a similar uptake in DU145-PSMA cells (29.3 ± 0.7%, 62% internalized). In contrast, [&lt;sup&gt;225&lt;/sup&gt;Ac]Ac-PSMA-617 exhibited lower uptake in both cell lines, with 1.6 ± 0.2% in LNCaP-AR cells and 4.6 ± 0.2% in DU145-PSMA cells after 4 h incubation. For all 3 radioligands, the uptake could be fully blocked by co-incubation with unlabeled PSMA-617 (300 nM), confirming the specificity of binding to PSMA, and the uptake was minimal in the paired PSMA-negative cell lines CWRR1-EnzR and DU145. In saturation binding assays, the three radioligands exhibited comparable binding affinities (&lt;i&gt;K&lt;/i&gt;&lt;sub&gt;D&lt;/sub&gt;) in LNCaP-AR and DU145-PSMA cell lines, with 5.9 ± 0.7 nM and 2.3 ± 0.3 nM for [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617, 5.7 ± 0.5 nM and 5.8 ± 0.9 nM for [&lt;sup&gt;225&lt;/sup&gt;Ac]Ac-PSMA-617, and 2.7 ± 0.5 nM and 8.0 ± 1.1 nM for [&lt;sup&gt;212&lt;/sup&gt;Pb]Pb-PSMA-617, respectively.&lt;/p&gt;&lt;h3&gt;Conclu","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00456-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969393","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":"Automated GMP production and long-term experience in radiosynthesis of the SV2A tracer [11C]UCB-J","authors":"Saara Wahlroos,&nbsp;Anna Krzyczmonik,&nbsp;Semi Helin,&nbsp;Johan Rajander,&nbsp;Olof Solin,&nbsp;Anna K. Kirjavainen","doi":"10.1186/s41181-025-00377-0","DOIUrl":"10.1186/s41181-025-00377-0","url":null,"abstract":"<div><h3>Background</h3><p>Positron emission tomography (PET) is a non-invasive imaging technique that enables the quantification of specific biological and pharmacological processes in vivo. PET can be used to investigate synaptic density by targeting synaptic vesicle glycoprotein 2A (SV2A), and can measure brain levels of SV2A in patients with epilepsy and other neurologic, neurodegenerative, or psychiatric conditions that involve SV2A. The well-known radiotracer [¹¹C]UCB-J ((<i>R</i>)-1-((3-[¹¹C]methylpyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) targets SV2A and thereby enables visualization of synaptic density in vivo.</p><h3>Results</h3><p>[¹¹C]UCB-J synthesis was performed using [¹¹C]methyl iodide ([¹¹C]CH₃I) produced with a commercial device. Here, we present an in-house-built device for [¹¹C]UCB-J production from [¹¹C]CH₃I and a suitably treated boronated precursor. The whole radiosynthetic procedure was automated, and has now been in clinical production according to GMP for more than four years. We also address several issues encountered during the production process development and tracer utilisation.</p><h3>Conclusions</h3><p>The developed method enables robust [¹¹C]UCB-J production, with a yield of 2.8 ± 0.6 GBq and molar activity of 150 ± 51 GBq/µmol (n = 56) at end of synthesis. The product fulfils all specifications set for a clinical tracer. GMP regulations and guidelines in all aspects of radiopharmaceutical preparation were followed. Although [¹¹C]UCB-J production is challenging, good and reliable radiochemical yields can be obtained by using a carefully designed production protocol.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-025-00377-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969342","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":"GMP-compliant automated synthesis and quality control of [177Lu]Lu-PSMA-I&T using the GAIA/LUNA Elysia-Raytest module for the treatment of metastatic castration-resistant prostate cancer","authors":"Amélie Coussirou,&nbsp;Mélodie Six,&nbsp;Agathe Edet-Sanson,&nbsp;Alice Salles,&nbsp;Pierre Vera,&nbsp;David Tonnelet,&nbsp;Pierre Bohn","doi":"10.1186/s41181-026-00455-x","DOIUrl":"10.1186/s41181-026-00455-x","url":null,"abstract":"<div><h3>Background</h3><p>Prostate cancer (PCa) has been identified as the most prevalent form of cancer among males and the third leading cause of death from cancer in the European male population. Early-stage PCa can be treated with prostatectomy and radiotherapy, whereas metastatic cases require androgen deprivation therapy and may benefit from targeted radionuclide therapy (TRT). The objective of our research is to develop and validate an automated production of [¹⁷⁷Lu]Lu-PSMA I&amp;T for clinical use. [¹⁷⁷Lu]Lu-PSMA I&amp;T is a radioligand therapy (RLT) that targets prostate-specific membrane antigen (PSMA), which is overexpressed in metastatic and castration-resistant prostate cancer.</p><h3>Results</h3><p>This work delineates the development and validation of analytical methodologies for the automated production of [¹⁷⁷Lu]Lu-PSMA I&amp;T with a GAIA-LUNA device from Elysia, in addition to the quality control measures implemented to ensure compliance with Good Manufacturing Practices and the European Pharmacopoeia. Three validation batches were produced, and the investigational medicinal product dossier was submitted to the French National Agency of Medicine and Health Products Safety (ANSM) for authorization. PSMA-I&amp;T was radiolabeled with ¹⁷⁷Lu using an automated radiosynthesis device, the GAIA-LUNA, from Elysia. Furthermore, we demonstrated the 72-h stability of the [¹⁷⁷Lu]Lu-PSMA I&amp;T preparations at room temperature, a development that facilitates the potential subcontracting of [¹⁷⁷Lu]Lu-PSMA I&amp;T production to other medical facilities.</p><h3>Conclusions</h3><p>The findings of this study underscore the potential of [¹⁷⁷Lu]Lu-PSMA I&amp;T as a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC) who have contraindications to chemotherapy or hormonotherapy, and highlight the importance of implementing rigorous quality control measures in the development of radiopharmaceuticals.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00455-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969334","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":"MUC1-targeting small peptide radiopharmaceuticals for breast cancer","authors":"Rim Malek,&nbsp;Madeleine Landry,&nbsp;Pierre Cheung,&nbsp;Corinne Beinat","doi":"10.1186/s41181-026-00451-1","DOIUrl":"10.1186/s41181-026-00451-1","url":null,"abstract":"<div><h3>Background</h3><p>Mucin 1 (MUC1) is a transmembrane glycoprotein overexpressed and underglycosylated in numerous epithelial cancers, including breast cancer. Reduced glycosylation leads to the exposure of the variable number tandem repeat (VNTR) region. To the best of our knowledge, all peptides previously described in the literature target the same epitope sequence of the VNTR. Given the high prevalence of breast cancer and the limited treatment options for the aggressive subtype triple-negative breast cancer (TNBC), due to its lack of oestrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2), we sought to develop a small peptide radiopharmaceutical targeting MUC1 by exploring all 3 minimal epitope sequences of the VNTR: RPAPGS, PPAHGVT and PDTRP. We also investigated the influence of linker lipophilicity on the binding affinity to MUC1.</p><h3>Results</h3><p>The reference compound <b>1</b> showed the highest cell uptake among all tested compounds. While some statistically significant differences were observed for the cell uptake between the different peptide sequences and the linkers, the uptake was so low that no reliable structure-activity relationships could be established. We then studied the specificity of all compounds for MUC1 by comparing the uptake in MUC1-expressing and MUC1-knockout (KO) cells, and unexpectedly observed no specificity for any compound. A saturation binding assay of several peptides showed their binding was too low to reliably determine their binding affinity (K_d). Surface plasmon resonance (SPR) further confirmed the absence of binding of all [^NatGa]- and [^NatLu]-labelled peptides tested. Given the discrepancies between our cell data and the previously reported results, we next assessed the specificity of the reference (<b>1</b>) in vivo in mice bearing MUC1-expressing and MUC1-knockdown (KD) tumours, which further proved its non-specificity.</p><h3>Conclusions</h3><p>While MUC1 is a very promising target for the development of breast cancer theranostics, designing peptidomimetics based on its minimal epitopes do not lead to high-affinity binders. Our ongoing efforts involve utilizing phage-display to identify new peptide sequences.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"11 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s41181-026-00451-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809472","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}