Nuclear medicine and biology最新文献

{"title":"Antimicrobial peptide LyeTx I mn∆K labeled with 68Ga is a potential PET radiopharmaceutical for molecular imaging of infections","authors":"Leonardo Lima Fuscaldi , Ana Claudia Ranucci Durante , Rosina Dapueto , Ana Laura Reyes , Andrea Paolino , Eduardo Savio , Luciana Malavolta , Maria Elena de Lima , Simone Odília Antunes Fernandes , Valbert Nascimento Cardoso , Marycel Figols de Barboza","doi":"10.1016/j.nucmedbio.2024.108966","DOIUrl":"10.1016/j.nucmedbio.2024.108966","url":null,"abstract":"<div><h3>Background</h3><div>Antimicrobial peptides have been radiolabeled and investigated as molecular diagnostic probes due to their propensity to accumulate in infectious sites rather than aseptic inflammatory lesions. LyeTx I is a cationic peptide from the venom of <em>Lycosa erythrognatha</em>, exhibiting significant antimicrobial activity. LyeTx I mn∆K is a shortened derivative of LyeTx I, with an optimized balance between antimicrobial and hemolytic activities. This study reports the first <sup>68</sup>Ga-radiolabeling of the DOTA-modified LyeTx I mn∆K and primarily preclinical evaluations of [<sup>68</sup>Ga]Ga-DOTA(K)-LyeTx I mn∆K as a PET radiopharmaceutical for infection imaging.</div></div><div><h3>Methods</h3><div>DOTA(K)-LyeTx I mn∆K was radiolabeled with freshly eluted <sup>68</sup>Ga. Radiochemical yield (RCY), radiochemical purity (RCP), and radiochemical stability (in saline and serum) were evaluated using ascending thin-layer chromatography (TLC) and reversed-phase high-performance liquid chromatography (RP-HPLC). The radiopeptide's lipophilicity was assessed by determining the logarithm of the partition coefficient (Log <em>P</em>). Serum protein binding (SBP) and binding to <em>Staphylococcus aureus</em> (<em>S. aureus</em>) cells were determined <em>in vitro</em>. <em>Ex vivo</em> biodistribution studies and PET/CT imaging were conducted in healthy mice (control) and mice with infection and aseptic inflammation to evaluate the potential of [<sup>68</sup>Ga]Ga-DOTA(K)-LyeTx I mn∆K as a specific PET radiopharmaceutical for infections.</div></div><div><h3>Results</h3><div>[<sup>68</sup>Ga]Ga-DOTA(K)-LyeTx I mn∆K was obtained with a high RCY (>90 %), and after purification through a Sep-Pak C18 cartridge, the RCP exceeded 99 %. Ascending TLC and RP-HPLC showed that the radiopeptide remained stable for up to 3.0 h in saline solution and up to 1.5 h in murine serum. [<sup>68</sup>Ga]Ga-DOTA(K)-LyeTx I mn∆K exhibited hydrophilic characteristics (Log <em>P</em> = −2.4 ± 0.1) and low SPB (ranging from 23.3 ± 0.4 % at 5 min of incubation to 10.5 ± 1.1 % at 60 min of incubation). The binding of [<sup>68</sup>Ga]Ga-DOTA(K)-LyeTx I mn∆K to <em>S. aureus</em> cells was proportional to bacterial concentration, with binding percentages of 8.8 ± 0.5 % (0.5 × 10<sup>9</sup> CFU<sup>.</sup>mL<sup>−1</sup>), 16.2 ± 1.4 % (1.0 × 10<sup>9</sup> CFU<sup>.</sup>mL<sup>−1</sup>), and 62.2 ± 0.6 % (5.0 × 10<sup>9</sup> CFU<sup>.</sup>mL<sup>−1</sup>). <em>Ex vivo</em> biodistribution studies and PET/CT images showed higher radiopeptide uptake at the infection site compared to the aseptic inflammation site; the latter was similar to the control group. Target-to-non-target (T/NT) ratios obtained by <em>ex vivo</em> biodistribution data were approximately 1.0, 1.3, and 3.0 at all investigated time intervals for the control, aseptic inflammation, and infection groups, respectively. Furthermore, T/NT ratios obtained from PET/CT images were 1.1 ± 0.1 f","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108966"},"PeriodicalIF":3.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obituary: P. August Schubiger, PhD (1945–2024)","authors":"Roger Schibli","doi":"10.1016/j.nucmedbio.2024.108964","DOIUrl":"10.1016/j.nucmedbio.2024.108964","url":null,"abstract":"","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108964"},"PeriodicalIF":3.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142425442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of PEGylation on HER2-targeting retro A9 peptide analogue","authors":"Sushree Arpitabala Yadav ,&nbsp;V. Kusum Vats ,&nbsp;Rohit Sharma ,&nbsp;Archana Mukherjee ,&nbsp;Drishty Satpati","doi":"10.1016/j.nucmedbio.2024.108963","DOIUrl":"10.1016/j.nucmedbio.2024.108963","url":null,"abstract":"<div><div>Elevated levels of HER2 receptor in breast cancer can be targeted through receptor-specific peptides for precise detection and therapy by nuclear medicine approach. Previously reported retro analogue of A9 peptide had shown HER2-specificity with promising pharmacokinetic features. Hence, with an aim of further improving the circulation time of rL-A9 radiopeptide, long polyethylene glycol chain (PEG₁₂) was introduced at the N-terminus of the peptide during solid phase synthesis and influence of PEGylation on biological profile was studied. [¹⁷⁷Lu]Lu-DOTA-PEG₁₂-rL-A9 demonstrated high specific cellular uptake (5.94 ± 0.09 %) in HER2-expressing human breast carcinoma SKBR3 cells and low nanomolar binding affinity (K_d = 34.58 ± 12.78 nM). Uptake in SKBR3 tumors induced in female SCID mice was higher at all the time points investigated (3, 24, 48 h) in comparison to the non-PEGylated radiopeptide, [¹⁷⁷Lu]Lu-DOTA-rL-A9. Blocking studies led to 51 % reduction in accumulation of radioactivity in the tumor indicating specificity of the radiopeptide. Improved tumor-to-stomach and tumor-to-intestine ratios for [¹⁷⁷Lu]Lu-DOTA-PEG₁₂-rL-A9 compared to [¹⁷⁷Lu]Lu-DOTA-rL-A9 at 48 h shall pave the way for better contrast and delineation of metastatic sites.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108963"},"PeriodicalIF":3.6,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal multimodal monitoring of transplanted islet β-cells","authors":"Filippo C. Michelotti ,&nbsp;Gregory Bowden ,&nbsp;Wael Eter ,&nbsp;Astrid Küppers ,&nbsp;Andreas Maurer ,&nbsp;Volker Nischwitz ,&nbsp;Bernd J. Pichler ,&nbsp;Martin Gotthardt ,&nbsp;Andreas M. Schmid","doi":"10.1016/j.nucmedbio.2024.108962","DOIUrl":"10.1016/j.nucmedbio.2024.108962","url":null,"abstract":"<div><h3>Purpose</h3><div>Monitoring β-cell mass and function would provide a better understanding of diabetes, setting the stage for truly individualized therapies. We applied a combined PET/MRI protocol to monitor engrafted islets mass and function without pre-labeling of isolated cells. A PET tracer binding to GLP-1R quantifies β-cell mass, while Mn-CA characterizes β-cell function. Both parameters were assessed in transplanted and native β-cells <em>in vivo</em> and validated with autoradiography and mass spectrometry imaging.</div></div><div><h3>Methods</h3><div>Islets were collected and transplanted into the calves of C3H-mice. Accumulation of [⁶⁴Cu]Ex4 and Mn-CA was examined with a PET/MRI at 1 h post-injection between 1 and 4 weeks after the transplantation. A separate blocking study with diazoxide targeted the functionality of the transplanted islets. As validation, <em>ex vivo</em> autoradiography and LA-ICP-MS imaging were performed after the last imaging session.</div></div><div><h3>Results</h3><div>PET/MRI monitored the engraftment of transplanted islets and visualized an increasing uptake of the PET tracer and Mn-CA<em>.</em> The Mn-CA accumulated at a higher islet-to-background ratio in the calf of mice than in the pancreas due to the high retention of Mn-CA in the exocrine pancreas. <em>In vivo</em> imaging data correlated well with autoradiography and LA-ICP-MS imaging, validating the <em>in vivo</em> approaches.</div></div><div><h3>Conclusion</h3><div>For the quantification of β-cell function, Mn-based contrast mechanisms between native and transplanted islets differ and require further studies for optimal biological readout. However, non-invasive PET/MRI nonetheless provides the tools to investigate the relationship between β-cell mass and function in pancreatic islets.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108962"},"PeriodicalIF":3.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrin-releasing peptide receptor as theranostic target in estrogen-receptor positive breast cancer: A preclinical study of the theranostic pair [55Co]Co- and [177Lu]Lu-DOTA-RM26","authors":"Christina Baun ,&nbsp;Birgitte Brinkmann Olsen ,&nbsp;Carla Maria Lourenco Alves ,&nbsp;Henrik Jørn Ditzel ,&nbsp;Mikkel Terp ,&nbsp;Malene Grubbe Hildebrandt ,&nbsp;Charlotte Aaberg Poulsen ,&nbsp;Lorraine Gaenaelle Gé ,&nbsp;Vigga Sand Gammelsrød ,&nbsp;Anna Orlova ,&nbsp;Johan Hygum Dam ,&nbsp;Helge Thisgaard","doi":"10.1016/j.nucmedbio.2024.108961","DOIUrl":"10.1016/j.nucmedbio.2024.108961","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Patients with advanced metastatic estrogen receptor-positive breast cancer often develop resistance to standard treatments, leading to uncontrolled progression. Thus, innovative therapies are urgently needed. The gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers, including breast cancer, making it an interesting theranostic target. RM26, a GRPR-targeting antagonist, has demonstrated promising &lt;em&gt;in vivo&lt;/em&gt; kinetics in prostate cancer models. This study evaluated the theranostic capabilities of [&lt;sup&gt;55&lt;/sup&gt;Co]Co−/[&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-RM26 &lt;em&gt;in vitro&lt;/em&gt; in estrogen receptor-positive breast cancer cells and assessed the diagnostic potential of [&lt;sup&gt;55&lt;/sup&gt;Co]Co-DOTA-RM26 &lt;em&gt;in vivo&lt;/em&gt; in a breast cancer mouse model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We analyzed the binding specificity of [&lt;sup&gt;57&lt;/sup&gt;Co]Co-/[&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-RM26 in T47D breast cancer cells, using [&lt;sup&gt;57&lt;/sup&gt;Co]Co-DOTA-RM26 as a surrogate for [&lt;sup&gt;55&lt;/sup&gt;Co]Co-DOTA-RM26. The therapeutic efficacy of increasing [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-RM26 concentrations was determined &lt;em&gt;via&lt;/em&gt; viability assay &lt;em&gt;in vitro. Ex vivo&lt;/em&gt; biodistribution of [&lt;sup&gt;57&lt;/sup&gt;Co]Co-DOTA-RM26 (17.2 ± 2.7 kBq, 33 ± 5.2 pmol/mouse) was investigated in 12 mice (&lt;em&gt;n&lt;/em&gt;= 4/group) with orthotopic breast cancer tumors. The mice were sacrificed at 4 and 24 h post-injection (pi), including a blocking group (20 nmol of unlabeled [Tyr4]-Bombesin) at 4 h pi. For imaging, two tumor-bearing mice underwent [&lt;sup&gt;55&lt;/sup&gt;Co]Co-DOTA-RM26 PET/CT, 4 and 24 h pi (2.8 ± 0.2 MBq, 167.5 ± 0.5 pmol/mouse), with or without GRPR blocking.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;em&gt;In vitro&lt;/em&gt; studies revealed high, specific binding of [&lt;sup&gt;57&lt;/sup&gt;Co]Co-DOTA-RM26 (43 ± 1 % of total added activity per 10&lt;sup&gt;6&lt;/sup&gt; cells (%IA/10&lt;sup&gt;6&lt;/sup&gt;)) and [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-RM26 (37 ± 4 %IA/10&lt;sup&gt;6&lt;/sup&gt;). The activity was predominantly localized at the cell surface: 71 ± 3 % and 80 ± 6 % for [&lt;sup&gt;57&lt;/sup&gt;Co]Co-DOTA-RM26 and [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-RM26, respectively. [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-DOTA-RM26 significantly reduced cell viability at all activity concentrations &gt;0.625 MBq/mL (&lt;em&gt;p&lt;/em&gt; &lt; 0.0001), with cell viability below 1 % at concentrations ≥5 MBq/mL. Biodistribution data (&lt;em&gt;n&lt;/em&gt; = 12) indicated a high, specific tumor uptake of [&lt;sup&gt;57&lt;/sup&gt;Co]Co-DOTA-RM26, surpassing all other tissues significantly at both time points, 3.7 ± 0.6 % of the injected activity per gram (%IA/g) 4 h pi and 0.98 ± 0.05 %IA/g 24 h pi. The kidneys showed the second-highest uptake (2.0 ± 0.1 %IA/g 4 h pi), followed by the pancreas (1.4 ± 0.4 %IA/g 4 h pi). PET/CT imaging with [&lt;sup&gt;55&lt;/sup&gt;Co]Co-DOTA-RM26 supported the biodistribution data and, distinctly visualized the tumor 24 h pi and showed an improved tumor-to-background compared to the earlier time points. Effective GRPR blocking significantly reduced tumor uptake in the PET images ","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108961"},"PeriodicalIF":3.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative [18F]fluoro-PEG-folate PET/CT in advanced stage epithelial ovarian cancer: A safety and feasibility study","authors":"Isabeau A. Ciggaar ,&nbsp;Lysanne D.A.N. de Muynck ,&nbsp;Lioe-Fee de Geus-Oei ,&nbsp;Floris H.P. van Velden ,&nbsp;Cornelis D. de Kroon ,&nbsp;Lenka M. Pereira Arias-Bouda ,&nbsp;Wyanne A. Noortman ,&nbsp;Els L. van Persijn van Meerten ,&nbsp;Petra Dibbets-Schneider ,&nbsp;Hendrik J.F. Helmerhorst ,&nbsp;Albert D. Windhorst ,&nbsp;Alexander L. Vahrmeijer ,&nbsp;Inge T.A. Peters ,&nbsp;Katja N. Gaarenstroom","doi":"10.1016/j.nucmedbio.2024.108952","DOIUrl":"10.1016/j.nucmedbio.2024.108952","url":null,"abstract":"<div><h3>Purpose</h3><div>The selection for either primary or interval cytoreductive surgery (CRS) in patients with epithelial ovarian cancer (EOC) is currently based on imaging techniques like computed tomography (CT), [¹⁸F]fluorodeoxyglucose-positron emission tomography ([¹⁸F]FDG-PET), diffusion-weighted magnetic resonance imaging (DW-MRI) and/or diagnostic laparoscopy, but these have limitations. Folate receptor (FR)-targeted PET/CT imaging, using [¹⁸F]fluoro-PEG-folate, could improve preoperative assessment, potentially reducing unnecessary laparotomies. This paper presents the first experience with [¹⁸F]fluoro-PEG-folate PET/CT imaging in advanced stage EOC, focusing on safety, tolerability, and feasibility for reflecting the extent of disease.</div></div><div><h3>Methods</h3><div>Tolerability and safety were monitored after administration of the [¹⁸F]fluoro-PEG-folate tracer by measurements of vital function parameters (blood pressure, heart rate, peripheral oxygen saturation, respiratory rate, and temperature). In addition, (serious) adverse events were recorded. Disease burden was quantified using the Peritoneal Cancer Index (PCI) score on preoperative [¹⁸F]fluoro-PEG-folate PET/CT and during surgery. PCI scores were compared with intraoperative findings, considering histopathologic results as the gold standard. Tissue specimens were stained for FRα and FRβ. Relative uptake of the radiotracer by EOC lesions and other tissues was quantified using body weighted standardized uptake values (SUV).</div></div><div><h3>Results</h3><div>The study was terminated prematurely during the interim analysis after inclusion of eight patients of whom five had completed the study protocol. Although [¹⁸F]fluoro-PEG-folate demonstrated safety, efficacy for tumor-specific imaging was limited. Despite clear FRα overexpression, low tracer uptake was observed in EOC lesions, contrasting with high uptake in healthy tissues, posing challenges in specificity and accurately assessing tumor burden.</div></div><div><h3>Conclusions</h3><div>Overall, while [¹⁸F]fluoro-PEG-folate was well-tolerated, its clinical utility in the preoperative assessment of the extent of disease in EOC was limited. This highlights the need for further research in developing targeted imaging agents for optimal detection of EOC metastases.</div><div>Trial registration: <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span>, NCT05215496. Registered 31 January 2022.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108952"},"PeriodicalIF":3.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of heterotopic ossification maturity using SPECT/CT and PET/CT in preclinical model","authors":"Shorouk Dannoon,&nbsp;Saud Alenezi,&nbsp;Abdelhamid Elgazzar","doi":"10.1016/j.nucmedbio.2024.108950","DOIUrl":"10.1016/j.nucmedbio.2024.108950","url":null,"abstract":"<div><h3>Background</h3><p>Heterotopic ossification (HO) is the formation of bone within soft tissue where bone normally does not exist. In general, it is characterized by highly active tissue with high bone turnover and rapid bone formation. It is of an utmost importance to precisely identify and accurately diagnose the maturity of HO as early surgical intervention may result in its recurrence. The objective of this work is the experimental evaluation of HO maturity stage using advanced noninvasive nuclear medicine techniques. The use of PET radiopharmaceuticals may result in a more specific diagnosis between the phases due to their higher sensitivity and better resolution compared to bone scan.</p></div><div><h3>Method</h3><p>8-week-old Balb/c male mice underwent dual injury procedure, tenotomy and concurrent burn injury on the left side, to induce HO. The progression of HO was monitored by SPECT/CT and PET/CT weekly imaging with ^99mTc-MDP, [¹⁸F]NaF and [¹⁸F]FDG for up to 16 weeks.</p></div><div><h3>Results</h3><p>There was a statistically significant increase of [¹⁸F]FDG uptake from week 1 to 2 and from week 2 to 6 with <em>p</em> values of 0.01 and 0.005; respectively, while there was a statistically significant decrease from week 7 to 14 with a <em>p</em> value of 0.008. There was a statistically significant increase of [¹⁸F]NaF uptake from week 2 to 5 and statistically significant decrease between weeks 7 and 14 with <em>p</em> values of 0.016 and 0.003; respectively. As for ^99mTc-MDP, the increase in the uptake from week 1 to 2 and from week 2 to 5 were not statistically significant with <em>p</em> values of 0.15 and 0.19; respectively. The decrease of uptake between week 7 and 14 was not statistically significant with a <em>p</em> value of 0.08.</p></div><div><h3>Conclusion</h3><p>Based on these findings, the use of noninvasive nuclear imaging modalities may assist in distinguishing between the immature and mature phases. The uptake of mainly [¹⁸F]FDG may indicate the early inflammatory phase, while the uptake of both [¹⁸F]FGD and [¹⁸F]NaF may suggest the immature phase, and an uptake of mainly [¹⁸F]NaF may indicate the maturity phase of HO.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108950"},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards imaging the immune state of cancer by PET: Targeting legumain with 11C-labeled P1-Asn peptidomimetics carrying a cyano-warhead","authors":"Severin K. Lustenberger ,&nbsp;Claudia A. Castro Jaramillo ,&nbsp;Lena A. Bärtschi ,&nbsp;Rich Williams ,&nbsp;Roger Schibli ,&nbsp;Linjing Mu ,&nbsp;Stefanie D. Krämer","doi":"10.1016/j.nucmedbio.2024.108951","DOIUrl":"10.1016/j.nucmedbio.2024.108951","url":null,"abstract":"<div><h3>Purpose</h3><p>M2-type tumor-associated macrophages (TAM) residing in the tumor microenvironment (TME) have been linked to tumor invasiveness, metastasis and poor prognosis. M2 TAMs suppress T cell activation, silencing the recognition of the cancer by the immune system. Targeting TAMs in anti-cancer therapy may support the immune system and immune-checkpoint inhibitor therapies to fight the cancer cells. We aimed to develop a PET tracer for the imaging of M2 TAM infiltration of cancer, using activated legumain as the imaging target.</p></div><div><h3>Basic procedures</h3><p>Two P1-mimicking inhibitors with a cyano-warhead were labeled with carbon-11 and evaluated <em>in vitro</em> and <em>in vivo</em> with a CT26 tumor mouse model. Target expression and activity were quantified from RT-qPCR and <em>in vitro</em> substrate conversion, respectively. The co-localization of legumain and TAMs was assessed by fluorescence microscopy. The two tracers were evaluated by PET with subsequent biodistribution analysis with the dissected tissues. Parent-to-total radioactivity in plasma was determined at several time points after i.v. tracer injection, using reverse phase radio-UPLC.</p></div><div><h3>Main findings</h3><p>Legumain displayed a target density of 40.7 ± 19.1 pmol per mg total protein in tumor lysate (<em>n</em> = 4) with high substrate conversion and colocalization with M2 macrophages in the tumor periphery. [¹¹C]<strong>1</strong> and [¹¹C]<strong>2</strong> were synthesized with &gt;95 % radiochemical purity and 12.9–382.2 GBq/μmol molar activity at the end of synthesis. We observed heterogeneous tumor accumulation in <em>in vitro</em> autoradiography and PET for both tracers. However, excess unlabeled <strong>1</strong> or <strong>2</strong> did not compete with tracer accumulation. Both [¹¹C]<strong>1</strong> and [¹¹C]<strong>2</strong> were rapidly metabolized to a polar radiometabolite <em>in vivo</em>.</p></div><div><h3>Principal conclusions</h3><p>The legumain tracers [¹¹C]<strong>1</strong> and [¹¹C]<strong>2</strong>, synthesized with high radiochemical purity and molar activity, accumulate in the legumain-positive CT26 tumor <em>in vivo</em>. However, the lack of competition by excess compound questions their specificity. Both tracers are rapidly metabolized <em>in vivo</em>, requiring structural modifications towards more stable tracers for further investigations.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108951"},"PeriodicalIF":3.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000775/pdfft?md5=e565835330dda2cc416d9d587895cf69&pid=1-s2.0-S0969805124000775-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automation of simplified two-step radiolabeling via ditosylate synthon for 18F-labeled radiotracers using AllinOne module","authors":"Shihong Li ,&nbsp;Alexander Schmitz ,&nbsp;Yu-Ting Lu ,&nbsp;Rammyani Pal ,&nbsp;Swarbhanu Sarkar ,&nbsp;Mark A. Sellmyer ,&nbsp;Robert H. Mach ,&nbsp;Hsiaoju Lee","doi":"10.1016/j.nucmedbio.2024.108948","DOIUrl":"10.1016/j.nucmedbio.2024.108948","url":null,"abstract":"<div><p>Direct fluorination of a tosylate or mesylate precursor has been a wide-spread and reliable way for radio-fluorination. This approach can be difficult to achieve when the precursor cannot be easily obtained or is chemically unstable. A possible alternative method is to radiolabel ethylene ditosylate or 1,3-propanediol di-p-tosylate to form a radiofluorinated synthon. Here we present the automation of a simplified and reliable approach for the two-step fluorination using [¹⁸F]FP-TMP, an analog of antibacterial agent trimethoprim. We demonstrate the feasibility of purifying the fluorinated synthon via filtration, and one final HPLC purification on a commercially available Trasis AllinOne module. The overall reaction time for the two-step reaction is around 90 min andthe decay-corrected yield for more than fifty preparations of [¹⁸F]FP-TMP is 22 ± 5 % with high radiochemical purity (≥ 90 %) and specific activities (147 ± 107 GBq/μmol). All batches passed pre-established quality control specifications, demonstrating the utility of using this method in tracer syntheses that meet good manufacturing practice (GMP) requirement. This method can be adopted to the syntheses of other radiotracers, such as [¹⁸F]FE-TMP, (+)-[¹⁸F]F-PHNO and [¹⁸F]FFMZ.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108948"},"PeriodicalIF":3.6,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of radiochemical purity: Cellular binding and internalization of different radiometal chlorides in prostate cancer cells","authors":"Julia Raitanen ,&nbsp;Lena Palm ,&nbsp;Marcus Hacker ,&nbsp;Theresa Balber ,&nbsp;Markus Mitterhauser","doi":"10.1016/j.nucmedbio.2024.108949","DOIUrl":"10.1016/j.nucmedbio.2024.108949","url":null,"abstract":"<div><p>Radiometals play an important role in nuclear medicine, both for imaging and therapy. Binding studies represent an important step in the development of new radiolabeled ligands, as valuable insights into the binding properties can be gained. However, this technique requires high radiochemical purity, otherwise results may lead to wrong assumptions or misinterpretations of affinities or uptake rates.</p><p>Therefore, this <em>in vitro</em> study aimed at investigating the cell binding and internalization characteristics of different radiometal chlorides ([¹¹¹In]InCl₃, [⁶⁸Ga]GaCl₃ and [¹⁷⁷Lu]LuCl₃) commonly applied in nuclear medicine, as well as the clinically applied [¹⁷⁷Lu]Lu-PSMA-I&amp;T in comparison, by using prostate cancer cells. PC-3 and LNCaP cells were incubated with 100 kBq of the respective radiometal chloride or [¹⁷⁷Lu]Lu-PSMA-I&amp;T for 1 h. For [¹⁷⁷Lu]LuCl₃, nuclei isolations and colloid determinations in saline and cell medium were also performed.</p><p>Results showed that [¹¹¹In]InCl₃ and [⁶⁸Ga]GaCl₃ bind and are internalized up to 3 % to PC-3 and LNCaP cells, whereas [¹⁷⁷Lu]LuCl₃ showed cell binding of up to 25 %, internalization up to 2.5 % and a nuclear uptake below 0.3 %. In comparison, [¹⁷⁷Lu]Lu-PSMA-I&amp;T showed only 3 % total cell binding to LNCaP cells. Further analysis of [¹⁷⁷Lu]LuCl₃ stability in NaCl and cell medium showed only low amounts of colloids, which are not increasing over time, and negligible unspecific binding to the used cell culture plates.</p><p>In conclusion, the results demonstrate the importance of high radiochemical purity, especially with regard to Lu-177 labeled compounds. Even if radiopharmaceuticals comply with common release-criteria, significant uptake can be derived from [¹⁷⁷Lu]LuCl₃ impurities and lead to wrong estimations of a compound's uptake behavior. Assuming an experimental result of 2 % membrane binding of the applied product, and 5 % residual [¹⁷⁷Lu]LuCl₃ in the final product (thereof 25 % membrane binding, as described above), would lead to 1.25 % membrane binding resulting from [¹⁷⁷Lu]LuCl₃ and only 0.75 % from the radiopharmaceutical.</p></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108949"},"PeriodicalIF":3.6,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969805124000751/pdfft?md5=9a72f23b8bbfaf501d8562748e7fcd91&pid=1-s2.0-S0969805124000751-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}