EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"cGMP compliant one-step, one-pot automated [18F]FBnTP production for clinical imaging of mitochondrial activity","authors":"Mai Lin,&nbsp;Cong-Dat Pham,&nbsp;Robert T. Ta,&nbsp;H. Charles Manning","doi":"10.1186/s41181-024-00274-y","DOIUrl":"10.1186/s41181-024-00274-y","url":null,"abstract":"<div><h3>Background</h3><p>4-[¹⁸F]fluorobenzyl-triphenylphosphonium ([¹⁸F]FBnTP) is a lipophilic cation PET tracer. The cellular uptake of [¹⁸F]FBnTP is correlated with oxidative phosphorylation by mitochondria, which has been associated with multiple critical diseases. To date, [¹⁸F]FBnTP has been successfully applied for imaging myocardial perfusion, assessment of severity of coronary artery stenosis, delineation of the ischemic area after transient coronary occlusion, and detection/quantification of apoptosis in various animal models. Recent preclinical and clinical studies have also expanded the possibilities of using [¹⁸F]FBnTP in oncological diagnosis and therapeutic monitoring. However, [¹⁸F]FBnTP is typically prepared through a tediously lengthy four-step, three-pot reaction and required multiple synthesizer modules; Thus, such an approach remains a challenge for this promising radiopharmaceutical to be implemented for routine clinical studies. Herein, we report an optimized one-step, one-pot automated approach to produce [¹⁸F]FBnTP through a single standard commercially-available radiosynthesizer that enables centralized production for clinical use.</p><h3>Results</h3><p>The fully automated production of [¹⁸F]FBnTP took less than 55 min with radiochemical yields ranging from 28.33 ± 13.92% (non-decay corrected), apparent molar activity of 69.23 ± 45.62 GBq/µmol, and radiochemical purities of 99.79 ± 0.41%. The formulated [¹⁸F]FBnTP solution was determined to be sterile and colorless with a pH of 4.0–6.0. Our data has indicated no observable radiolysis after 8 h from the time of final product formulation and maximum assay of 7.88 GBq.</p><h3>Conclusions</h3><p>A simplified and cGMP-compliant radiosynthesis of [¹⁸F]FBnTP has been established on the commercially available synthesizer in high activity concentration and radiochemical purity. While the preclinical and clinical studies using [¹⁸F]FBnTP PET are currently underway, the automated approaches reported herein facilitate clinical adoption of this radiotracer and warrant centralized production of [¹⁸F]FBnTP for imaging multiple patients.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454428","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 radiosynthesis and preclinical evaluation of two new PSMA-617 derivatives radiolabelled via [18F]AlF2+ method","authors":"Marco Nicola Iannone,&nbsp;Silvia Valtorta,&nbsp;Stefano Stucchi,&nbsp;Stefano Altomonte,&nbsp;Elia Anna Turolla,&nbsp;Elisa Vino,&nbsp;Paolo Rainone,&nbsp;Valentina Zecca,&nbsp;Alessia Lo Dico,&nbsp;Marco Maspero,&nbsp;Mariangela Figini,&nbsp;Matteo Bellone,&nbsp;Samuele Ciceri,&nbsp;Diego Colombo,&nbsp;Clizia Chinello,&nbsp;Lisa Pagani,&nbsp;Rosa Maria Moresco,&nbsp;Sergio Todde,&nbsp;Patrizia Ferraboschi","doi":"10.1186/s41181-024-00280-0","DOIUrl":"10.1186/s41181-024-00280-0","url":null,"abstract":"<div><h3>Background</h3><p>In the last decade the development of new PSMA-ligand based radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research. The most promising derivative in terms of interaction with the antigen and clinical properties has been found to be “PSMA-617”, and its lutetium-177 radiolabelled version has recently been approved by EU and USA regulatory agencies for therapeutic purposes. For the above reasons, the development of new derivatives of PSMA-617 radiolabelled with fluorine-18 may still be of great interest. This paper proposes the comparison of two different PSMA-617 derivatives functionalized with NODA and RESCA chelators, respectively, radiolabelled via [¹⁸F]AlF²⁺ complexation.</p><h3>Results</h3><p>The organic synthesis of two PSMA-617 derivatives and their radiolabelling via [¹⁸F]AlF²⁺ complexation resulted to proceed efficiently and successfully. Moreover, stability in solution and in plasma has been evaluated. The whole radiosynthesis procedure has been fully automated, and the final products have been obtained with radiochemical yield and purity potentially suitable for clinical studies. The biodistribution of the two derivatives was performed both in prostate cancer and glioma tumour models. Compared with the reference [¹⁸F]F-PSMA-1007 and [¹⁸F]F-PSMA-617-RESCA, [¹⁸F]F-PSMA-617-NODA derivative showed a higher uptake in both tumors, faster clearance in non-target organs, and lower uptake in salivary glands.</p><h3>Conclusion</h3><p>PSMA-617 NODA and RESCA derivatives were radiolabelled successfully via [¹⁸F]AlF²⁺ chelation, the former being more stable in solution and human plasma. Moreover, preclinical biodistribution studies showed that [¹⁸F]F-PSMA-617-NODA might be of potential interest for clinical applications.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00280-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431065","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":"Recently developed radiopharmaceuticals for bacterial infection imaging","authors":"Maryke Kahts,&nbsp;Beverley Summers,&nbsp;Aadil Gutta,&nbsp;Wilfrid Pilloy,&nbsp;Thomas Ebenhan","doi":"10.1186/s41181-024-00279-7","DOIUrl":"10.1186/s41181-024-00279-7","url":null,"abstract":"<div><h3>Background</h3><p>Infection remains a major cause of morbidity and mortality, regardless of advances in antimicrobial therapy and improved knowledge of microorganisms. With the major global threat posed by antimicrobial resistance, fast and accurate diagnosis of infections, and the reliable identification of intractable infection, are becoming more crucial for effective treatment and the application of antibiotic stewardship. Molecular imaging with the use of nuclear medicine allows early detection and localisation of infection and inflammatory processes, as well as accurate monitoring of treatment response. There has been a continuous search for more specific radiopharmaceuticals to be utilised for infection imaging. This review summarises the most prominent discoveries in specifically bacterial infection imaging agents over the last five years, since 2019.</p><h3>Main body</h3><p>Some promising new radiopharmaceuticals evaluated in patient studies are reported here, including radiolabelled bacterial siderophores like [⁶⁸Ga]Ga-DFO-B, radiolabelled antimicrobial peptide/peptide fragments like [⁶⁸Ga]Ga-NOTA-UBI29-41, and agents that target bacterial synthesis pathways (folic acid and peptidoglycan) like [¹¹C]para-aminobenzoic acid and D-methyl-[¹¹C]-methionine, with clinical trials underway for [¹⁸F]fluorodeoxy-sorbitol, as well as for ¹¹C- and ¹⁸F-labelled trimethoprim.</p><h3>Conclusion</h3><p>It is evident that a great deal of effort has gone into the development of new radiopharmaceuticals for infection imaging over the last few years, with remarkable progress in preclinical investigations. However, translation to clinical trials, and eventually clinical Nuclear Medicine practice, is apparently slow. It is the authors’ opinion that a more structured and harmonised preclinical setting and well-designed clinical investigations are the key to reliably evaluate the true potential of the newly proposed infection imaging agents.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00279-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417132","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":"In vivo stable 211At-labeled prostate-specific membrane antigen-targeted tracer using a neopentyl glycol structure","authors":"Hiroyuki Suzuki,&nbsp;Kento Kannaka,&nbsp;Mizuki Hirayama,&nbsp;Tomoki Yamashita,&nbsp;Yuta Kaizuka,&nbsp;Ryota Kobayashi,&nbsp;Takahiro Yasuda,&nbsp;Kazuhiro Takahashi,&nbsp;Tomoya Uehara","doi":"10.1186/s41181-024-00278-8","DOIUrl":"10.1186/s41181-024-00278-8","url":null,"abstract":"<div><h3>Background</h3><p>Prostate cancer is a common cancer among men worldwide that has a very poor prognosis, especially when it progresses to metastatic castration-resistant prostate cancer (mCRPC). Therefore, novel therapeutic agents for mCRPC are urgently required. Because prostate-specific membrane antigen (PSMA) is overexpressed in mCRPC, targeted alpha therapy (TAT) for PSMA is a promising treatment for mCRPC. Astatine-211 (²¹¹At) is a versatile α-emitting radionuclide that can be produced using a cyclotron. Therefore, ²¹¹At-labeled PSMA compounds could be useful for TAT; however, ²¹¹At-labeled compounds are unstable against deastatination in vivo. In this study, to develop in vivo stable ²¹¹At-labeled PSMA derivatives, we designed and synthesized ²¹¹At-labeled PSMA derivatives using a neopentyl glycol (NpG) structure that can stably retain ²¹¹At in vivo. We also evaluated their biodistribution in normal and tumor-bearing mice.</p><h3>Results</h3><p>We designed and synthesized ²¹¹At-labeled PSMA derivatives containing two glutamic acid (Glu) linkers between the NpG structure and asymmetric urea (NpG-L-PSMA ((L-Glu)₂ linker used) and NpG-D-PSMA ((D-Glu)₂ linker used)). First, we evaluated the characteristics of ¹²⁵I-labeled NpG derivatives because ¹²⁵I was readily available. [¹²⁵I]I-NpG-L-PSMA and [¹²⁵I]I-NpG-D-PSMA showed low accumulation in the stomach and thyroid, indicating their high in vivo stability against deiodination. [¹²⁵I]I-NpG-L-PSMA was excreted in urine as hydrophilic radiometabolites in addition to the intact form. Meanwhile, [¹²⁵I]I-NpG-D-PSMA was excreted in urine in an intact form. In both cases, no radioactivity was observed in the free iodine fraction. [¹²⁵I]I-NpG-D-PSMA showed higher tumor accumulation than [¹²⁵I]I-NpG-L-PSMA. We then developed ²¹¹At-labeled PSMA using the NpG-D-PSMA structure. [²¹¹At]At-NpG-D-PSMA showed low accumulation in the stomach and thyroid in normal mice, indicating its high stability against deastatination in vivo. Moreover, [²¹¹At]At-NpG-D-PSMA showed high accumulation in tumor similar to that of [¹²⁵I]I-NpG-D-PSMA.</p><h3>Conclusions</h3><p>[²¹¹At]At-NpG-D-PSMA showed high in vivo stability against deastatination and high tumor accumulation. [²¹¹At]At-NpG-D-PSMA should be considered as a potential new TAT for mCRPC.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00278-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330008","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":"Trans-cyclooctene—a Swiss army knife for bioorthogonal chemistry: exploring the synthesis, reactivity, and applications in biomedical breakthroughs","authors":"Karuna Adhikari,&nbsp;Maarten Vanermen,&nbsp;Gustavo Da Silva,&nbsp;Tim Van den Wyngaert,&nbsp;Koen Augustyns,&nbsp;Filipe Elvas","doi":"10.1186/s41181-024-00275-x","DOIUrl":"10.1186/s41181-024-00275-x","url":null,"abstract":"<div><h3>Background</h3><p><i>Trans</i>-cyclooctenes (TCOs) are highly strained alkenes with remarkable reactivity towards tetrazines (Tzs) in inverse electron-demand Diels–Alder reactions. Since their discovery as bioorthogonal reaction partners, novel TCO derivatives have been developed to improve their reactivity, stability, and hydrophilicity, thus expanding their utility in diverse applications.</p><h3>Main body</h3><p>TCOs have garnered significant interest for their applications in biomedical settings. In chemical biology, TCOs serve as tools for bioconjugation, enabling the precise labeling and manipulation of biomolecules. Moreover, their role in nuclear medicine is substantial, with TCOs employed in the radiolabeling of peptides and other biomolecules. This has led to their utilization in pretargeted nuclear imaging and therapy, where they function as both bioorthogonal tags and radiotracers, facilitating targeted disease diagnosis and treatment. Beyond these applications, TCOs have been used in targeted cancer therapy through a \"click-to-release\" approach, in which they act as key components to selectively deliver therapeutic agents to cancer cells, thereby enhancing treatment efficacy while minimizing off-target effects. However, the search for a suitable TCO scaffold with an appropriate balance between stability and reactivity remains a challenge.</p><h3>Conclusions</h3><p>This review paper provides a comprehensive overview of the current state of knowledge regarding the synthesis of TCOs, and its challenges, and their development throughout the years. We describe their wide ranging applications as radiolabeled prosthetic groups for radiolabeling, as bioorthogonal tags for pretargeted imaging and therapy, and targeted drug delivery, with the aim of showcasing the versatility and potential of TCOs as valuable tools in advancing biomedical research and applications.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00275-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282653","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 evaluation of [18F]FBNAF, a STAT3-targeting probe, for PET imaging of tumor microenvironment","authors":"Anna Miyazaki,&nbsp;Yasukazu Kanai,&nbsp;Keita Wakamori,&nbsp;Serina Mizuguchi,&nbsp;Mikiya Futatsugi,&nbsp;Fuko Hirano,&nbsp;Naoya Kondo,&nbsp;Takashi Temma","doi":"10.1186/s41181-024-00276-w","DOIUrl":"10.1186/s41181-024-00276-w","url":null,"abstract":"<div><h3>Background</h3><p>Signal transducer and activator of transcription 3 (STAT3) is a protein that regulates cell proliferation and differentiation, and it is attracting attention as a new index for evaluating cancer pathophysiology, as its activation has been highly correlated with the development and growth of tumors. With the development of STAT3 inhibitors, the demand for imaging probes will intensify. Noninvasive STAT3 imaging can help determine the cancer status and predict the efficacy of STAT3 inhibitors. In this study, we aimed to develop an imaging probe targeting STAT3 and synthesized [¹⁸F]FBNAF, which was derived from a STAT3-selective inhibitor as the lead compound, followed by in vitro and in vivo evaluations of [¹⁸F]FBNAF in positron emission tomography for STAT3.</p><h3>Results</h3><p>The results revealed that FBNAF concentration-dependently inhibited STAT3 phosphorylation, similar to the lead compound, thereby supporting radiosynthesis. [¹⁸F]FBNAF was easily synthesized from the pinacol boronate ester precursor with suitable radiochemical conversion (46%), radiochemical yield (6.0%), and radiochemical purity (&gt; 97%). [¹⁸F]FBNAF exhibited high stability in vitro and in vivo, and radioactivity accumulated in tumor tissues expressing STAT3 with an increasing tumor/blood ratio over time, peaking at 2.6 ± 0.8 at 120 min after injection in tumor-bearing mice. Tumor radioactivity was significantly reduced by the coinjection of a STAT3-selective inhibitor. Furthermore, the localization of radioactivity was almost consistent with STAT3 expression based on ex vivo autoradiography and immunohistochemistry using adjacent tumor sections.</p><h3>Conclusions</h3><p>Thus, [¹⁸F]FBNAF could be the first promising STAT3-targeting probe for PET imaging. A STAT3 imaging probe provides meaningful information on STAT3-associated cancer conditions and in tumor microenvironment.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00276-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246909","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":"Step-by-step optimisation of the radiosynthesis of the brain HDAC6 radioligand [18F]FSW-100 for clinical applications","authors":"Tetsuro Tago,&nbsp;Jun Toyohara","doi":"10.1186/s41181-024-00277-9","DOIUrl":"10.1186/s41181-024-00277-9","url":null,"abstract":"<div><h3>Background</h3><p>Histone deacetylase 6 (HDAC6) is an emerging target for the treatment and diagnosis of proteinopathies. [¹⁸F]FSW-100 was recently developed as a promising brain-penetrating radioligand for HDAC6 PET imaging and the process validation of [¹⁸F]FSW-100 radiosynthesis for clinical use is complete, but no detailed synthetic strategy nor process optimisation has been reported. Here, we describe the optimisation of several processes in [¹⁸F]FSW-100 radiosynthesis, including the ¹⁸F-fluorination reaction, semipurification of the ¹⁸F-intermediate, and purification of the product by high-performance liquid chromatography (HPLC), to achieve a radiochemical yield (RCY) adequate for clinical applications of the radioligand. Our findings will aid optimisation of radiosynthesis processes in general.</p><h3>Results</h3><p>In the ¹⁸F-fluorination reaction, the amount of copper reagent was reduced without reducing the nonisolated RCY of the intermediate (50%), thus reducing the risk of copper contamination in the product injection solution. Optimising the solid-phase extraction (SPE) conditions for semipurification of the intermediate improved its recovery efficiency. The addition of anti-radiolysis reagents to the mobile phase for the HPLC purification of [¹⁸F]FSW-100 increased its activity yield in radiosynthesis using a high [¹⁸F]fluoride radioactivity of approximately 50 GBq. The SPE-based formulation method and additives for the injection solution were optimised, and the resulting [¹⁸F]FSW-100 injection solution was stable for over 2 h with a radiochemical purity of greater than 95%.</p><h3>Conclusions</h3><p>Of all the reconsidered processes, we found that optimisation of the SPE-based semipurification of the intermediate and of the mobile phase for HPLC purification in particular improved the RCY of [¹⁸F]FSW-100, doubling it compared to that of the original protocol. The radioactivity of [¹⁸F]FSW-100 synthesized using the optimized protocol was sufficient for multiple doses for a clinical study.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00277-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236634","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":"eTFC-01: a dual-labeled chelate-bridged tracer for SSTR2-positive tumors","authors":"Dylan Chapeau,&nbsp;Savanne Beekman,&nbsp;Maryana Handula,&nbsp;Erika Murce,&nbsp;Corrina de Ridder,&nbsp;Debra Stuurman,&nbsp;Yann Seimbille","doi":"10.1186/s41181-024-00272-0","DOIUrl":"10.1186/s41181-024-00272-0","url":null,"abstract":"<div><h3>Background</h3><p>Integrating radioactive and optical imaging techniques can facilitate the prognosis and surgical guidance for cancer patients. Using a single dual-labeled tracer ensures consistency in both imaging modalities. However, developing such molecule is challenging due to the need to preserve the biochemical properties of the tracer while introducing bulky labeling moieties. In our study, we designed a trifunctional chelate that facilitates the coupling of the targeting vector and fluorescent dye at opposite sites to avoid undesired steric hindrance effects. The synthesis of the trifunctional chelate N₃-Py-DOTAGA-(tBu)₃ (<b>7</b>) involved a five-step synthetic route, followed by conjugation to the linear peptidyl-resin <b>8</b> through solid-phase synthesis. After deprotection and cyclization, the near-infrared fluorescent dye sulfo-Cy.5 was introduced using copper free click chemistry, resulting in <b>eTFC-01</b>. Subsequently, <b>eTFC-01</b> was labeled with [¹¹¹In]InCl₃. In vitro assessments of eTFC-01 binding, uptake, and internalization were conducted in SSTR2-transfected U2OS cells. Ex-vivo biodistribution and fluorescence imaging were performed in H69-tumor bearing mice.</p><h3>Results</h3><p><b>eTFC-01</b> demonstrated a two-fold higher IC50 value for SSTR2 compared to the gold standard DOTA-TATE. Labeling of <b>eTFC-01</b> with [¹¹¹In]InCl₃ gave a high radiochemical yield and purity. The uptake of [¹¹¹In]In-<b>eTFC-01</b> in U2OS.SSTR2 cells was two-fold lower than the uptake of [¹¹¹In]In-DOTA-TATE, consistent with the binding affinity. Tumor uptake in H69-xenografted mice was lower for [¹¹¹In]In-<b>eTFC-01</b> at all-time points compared to [¹¹¹In]In-DOTA-TATE. Prolonged blood circulation led to increased accumulation of [¹¹¹In]In-<b>eTFC-01</b> in highly vascularized tissues, such as lungs, skin, and heart. Fluorescence measurements in different organs correlated with the radioactive signal distribution.</p><h3>Conclusion</h3><p>The successful synthesis and coupling of the trifunctional chelate to the peptide and fluorescent dye support the potential of this synthetic approach to generate dual labeled tracers. While promising in vitro, the in vivo results obtained with [¹¹¹In]In-<b>eTFC-01</b> suggest the need for adjustments to enhance tracer distribution.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00272-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074895","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":"In vitro and in vivo evaluation of a tetrazine-conjugated poly-L-lysine effector molecule labeled with astatine-211","authors":"Chiara Timperanza,&nbsp;Holger Jensen,&nbsp;Ellinor Hansson,&nbsp;Tom Bäck,&nbsp;Sture Lindegren,&nbsp;Emma Aneheim","doi":"10.1186/s41181-024-00273-z","DOIUrl":"10.1186/s41181-024-00273-z","url":null,"abstract":"<div><h3>Background</h3><p>A significant challenge in cancer therapy lies in eradicating hidden disseminated tumor cells. Within Nuclear Medicine, Targeted Alpha Therapy is a promising approach for cancer treatment tackling disseminated cancer. As tumor size decreases, alpha-particles gain prominence due to their high Linear Energy Transfer (LET) and short path length. Among alpha-particle emitters, ²¹¹At stands out with its 7.2 hour half-life and 100% alpha emission decay. However, optimizing the pharmacokinetics of radiopharmaceuticals with short lived radionuclides such as ²¹¹At is pivotal, and in this regard, pretargeting is a valuable tool. This method involves priming the tumor with a modified monoclonal antibody capable of binding both the tumor antigen and the radiolabeled carrier, termed the “effector molecule. This smaller, faster-clearing molecule improves efficacy. Utilizing the Diels Alder click reaction between Tetrazine (Tz) and Trans-cyclooctene (TCO), the Tz-substituted effector molecule combines seamlessly with the TCO-modified antibody. This study aims to evaluate the in vivo biodistribution of two Poly-L-Lysine-based effector molecule sizes (10 and 21 kDa), labelled with ²¹¹At, and the in vitro binding of the most favorable polymer size, in order to optimize the pretargeted radioimmunotherapy with ²¹¹At.</p><h3>Results</h3><p>In vivo results favor the smaller polymer’s biodistribution pattern over the larger one, which accumulates in organs like the liver and spleen. This is especially evident when comparing the biodistribution of the smaller polymer to a directly labelled monoclonal antibody. The smaller variant also shows rapid and efficient binding to SKOV-3 cells preloaded with TCO-modified Trastuzumab in vitro, emphasizing its potential. Both polymer sizes showed equal or better in vivo stability of the astatine-carbon bond compared to a monoclonal antibody labelled with the same prosthetic group.</p><h3>Conclusions</h3><p>Overall, the small Poly-L-Lysine-based effector molecule (10 kDa) holds the most promise for future research, exhibiting significantly lower uptake in the kidneys and spleen compared to the larger effector (21 kDa) while maintaining an in vivo stability of the astatine-carbon bond comparable to or better than intact antibodies. A proof of concept in vitro cell study demonstrates rapid reaction between the small astatinated effector and a TCO-labelled antibody, indicating the potential of this novel Poly-L-Lysine-based pretargeting system for further investigation in an in vivo tumor model.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00273-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074846","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":"Highlight selection of radiochemistry and radiopharmacy developments by editorial board","authors":"Jun Toyohara,&nbsp;Danielle Vugts,&nbsp;Oliver C. Kiss,&nbsp;Sergio Todde,&nbsp;Xiang-Guo Li,&nbsp;Zhibo Liu,&nbsp;Zhi Yang,&nbsp;Nic Gillings,&nbsp;Emiliano Cazzola,&nbsp;Wiktor Szymanski,&nbsp;Nick van der Meulen,&nbsp;Raymond Reilly,&nbsp;Carlotta Taddei,&nbsp;Ralf Schirrmacher,&nbsp;Zijing Li,&nbsp;Yohannes Jorge Lagebo,&nbsp;Naoual Bentaleb,&nbsp;Marta de Souza Albernaz,&nbsp;Suzanne Lapi,&nbsp;Caterina Ramogida,&nbsp;Archana Mukherjee,&nbsp;Javier Ajenjo,&nbsp;Winnie Deuther-Conrad,&nbsp;Cécile Bourdeau","doi":"10.1186/s41181-024-00268-w","DOIUrl":"10.1186/s41181-024-00268-w","url":null,"abstract":"","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00268-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943751","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}