EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Automated radiofluorination of HER2 single domain antibody: the road towards the clinical translation of [18F]FB-HER2 sdAb","authors":"Herlinde Dierick,&nbsp;Laurent Navarro,&nbsp;Sonja Van den Block,&nbsp;Jelena Saliën,&nbsp;Tony Lahoutte,&nbsp;Vicky Caveliers,&nbsp;Jessica Bridoux","doi":"10.1186/s41181-024-00306-7","DOIUrl":"10.1186/s41181-024-00306-7","url":null,"abstract":"<div><h3>Background</h3><p>With the next generation of Human Epidermal Growth Factor Receptor 2 (HER2) -targeting therapies, such as antibody–drug conjugates, showing benefit in “HER2 low” and even “HER2 ultralow” patients, the need for novel methods to quantify HER2 expression accurately becomes even more important for clinical decision making. A HER2 PET/CT imaging assessment could evaluate HER2 positive disease locations while improving patient care, reducing the need for invasive biopsies. A single-domain antibody (sdAb)-based PET tracer could combine the high specificity of sdAbs with short-lived radionuclides such as fluorine-18 (¹⁸F) and gallium-68 (⁶⁸Ga). SdAb-based PET tracers have clinically been used via a ⁶⁸Ga-chelator approach. However, the distribution of ⁶⁸Ga-labelled pharmaceuticals to peripheral PET centres is more challenging to organize due to the short half-life of ⁶⁸Ga, most certainly when the available activity is limited by a generator. Cyclotron produced ⁶⁸Ga has removed this limitation. Distribution of ¹⁸F-labelled pharmaceuticals remains less challenging due to its slightly longer half-life, and radiofluorination of sdAbs via<i> N</i>-succinimidyl-4-[¹⁸F]fluorobenzoate ([¹⁸F]SFB) has shown to be a promising strategy for developing sdAb-based PET tracers. Although [¹⁸F]SFB automation has been reported, automating protein conjugation proves challenging. Herein we report the fully automated, cartridge-based production of [¹⁸F]FB-HER2 sdAb on a single synthesis module.</p><h3>Results</h3><p>[¹⁸F]FB-HER2 sdAb (&gt; 6 GBq) was obtained after a fully automated production (95 min), with a RCP &gt; 95%, apparent molar activity &gt; 20 GBq/µmol and decay-corrected radiochemical yield (RCY d.c.) of 14 ± 2% (n = 4). Further upscaling amounted to production batches of 16 GBq with an apparent molar activity &gt; 40 GBq/µmol and RCY d.c. of 8 ± 1% (n = 4). Ex vivo biodistribution and PET imaging showed specific HER2-positive tumour targeting and low kidney retention.</p><h3>Conclusion</h3><p>The [¹⁸F]FB-HER2 sdAb tracer was produced with clinically relevant activities using a fully automated production method. The automated production method was designed to ease the translation to the clinic and has the potential to be used not only in mono-centre but also multi-centre clinical trials with one central production site. [¹⁸F]FB-HER2 sdAb showed a favourable biodistribution pattern and could be a valuable alternative to ⁶⁸Ga-labelled sdAb-based PET tracers in the clinic.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00306-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611912","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":"Modified poly-L-lysine for use as a clearing agent in pretargeted radioimmunotherapy","authors":"Chiara Timperanza,&nbsp;Anna Gustafsson-Lutz,&nbsp;Tom Bäck,&nbsp;Damian J. Green,&nbsp;Sture Lindegren,&nbsp;Emma Aneheim","doi":"10.1186/s41181-024-00307-6","DOIUrl":"10.1186/s41181-024-00307-6","url":null,"abstract":"<div><h3>Background</h3><p>Pretargeted radioimmunotherapy of cancer has the potential to increase tumor specific uptake of activity when compared with conventional radioimmunotherapy. This is especially true in radioimmunotherapy with nuclides that exhibit a relatively short half-life. When administering antibody-based pretargeting molecules systemically, the antibodies often show a relatively slow clearance from the blood. Therefore, the use of a clearing agent is advantageous to remove unbound pretargeting molecules from the circulation, facilitating a reduction in the nonspecific radiation exposure to normal tissue while maximizing the dose delivered to the tumors.</p><h3>Results</h3><p>In the current study, two types of poly-L-lysine based clearing agents were produced for two different pretargeting systems: (strept)avidin/biotin and Tetrazine/Transcyclooctene. Poly-L-lysine was used as scaffold for production of clearing agents. The polymer is available in multiple sizes and can readily be modified with several functional groups, allowing different pretargeting strategies to be used. In vivo evaluation of the biotin-functionalized poly-L-lysine clearing agent, 110 repeating units, resulted in a decrease in blood concentration of the Iodine-125 labeled pretargeting agent of 50%, circa 23 h after injection, compared to controls. Two sizes, 68 and 143 repeating units, of the tetrazine-functionalized poly-L-lysine clearing agent were also evaluated, which at 23 h after injection decreased the blood concentration of the Iodine-125 labeled pretargeting agent to 58 and 38% respectively.</p><h3>Conclusion</h3><p>The straightforward synthesis of poly-L-lysine based clearing agents makes kit preparation possible and these agents show good potential for further evaluation, especially within the Tetrazine/Transcyclooctene pretargeting system where no liver or kidney accumulation was observed.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00307-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611914","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":"Exploring a tristhione scorpionate ligand as a suitable chelator for the theranostic pair antimony-119 and antimony-117","authors":"Lorraine Gaenaelle Gé,&nbsp;Mads Sondrup Møller,&nbsp;Catherine Chen,&nbsp;Virginia Cendán Castillo,&nbsp;Niels Langkjaer,&nbsp;Vickie McKee,&nbsp;Johan Hygum Dam,&nbsp;Christine J. McKenzie,&nbsp;Helge Thisgaard","doi":"10.1186/s41181-024-00297-5","DOIUrl":"10.1186/s41181-024-00297-5","url":null,"abstract":"<div><h3>Background</h3><p>The highly potent Auger electron emitter antimony-119 (¹¹⁹Sb) and the SPECT-isotope antimony-117 (¹¹⁷Sb) comprise a true theranostic pair particularly suitable for cancer theranostics. Harnessing this potential requires development of a chelator that can rapidly form a stable complex with radioactive antimony ions at the low concentrations typical of radiopharmaceutical preparations. Stable Sb(III) complexes of hydrotris(methimazolyl)borate (TMe) are known, prompting our investigation of this chelator. Additionally, the production of radioantimony was optimized and the SPECT imaging properties of ¹¹⁷Sb was investigated, in an attempt to move towards biomedical implementation of the theranostic isotope pair of antimony.</p><h3>Results</h3><p>A method for rapid and effective labelling of TMe using ¹¹⁷Sb was developed, yielding high radiochemical purities of 98.5 ± 2.7% and high radionuclidic purities exceeding 99%. Radiolabelling yielded an Sb(III) complex directly from the acidic Sb(V) solution. [^1XXSb]Sb-TMe in aqueous acidic solution showed high stability in the presence of cysteine, however, the stability of the radiocomplex at increased pH was significantly decreased. The production method of ¹¹⁷Sb was optimized, enabling a production yield of up to 19.6 MBq/µAh and the production of up to 564 MBq at end of bombardment, following irradiation of a thin ¹¹⁷Sn-enriched solid target. Preclinical SPECT/CT scanning of a mouse phantom containing purified ¹¹⁷Sb demonstrated excellent SPECT imaging properties of ¹¹⁷Sb with high spatial resolution comparable to that of technetium-99m.</p><h3>Conclusion</h3><p>We have explored the TMe chelator for complexation of radioantimony and devised a rapid chelation protocol suitable for the short half-life of ¹¹⁷Sb (T_1/2 = 2.8 h). [^1XXSb]Sb-TMe (^1XXSb = ¹¹⁷Sb, ^118mSb, ^120mSb and ¹²²Sb) demonstrated a high stability in presence of cysteine, although low stability was observed at pH &gt; 4. We have achieved a production yield of ¹¹⁷Sb high enough for clinical applications and demonstrated the excellent SPECT-imaging properties of ¹¹⁷Sb. The results contribute valuable information for the development of suitable chelators for radioantimony and is a step further towards implementation of the antimony theranostic pair in biomedical applications.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00297-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142579348","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 nanoprobes radiolabelled with 99mTc for the diagnosis and monitoring of therapeutic interventions in oncology preclinical research","authors":"María Jimena Salgueiro,&nbsp;Mariano Portillo,&nbsp;Fiorella Tesán,&nbsp;Melisa Nicoud,&nbsp;Vanina Medina,&nbsp;Marcela Moretton,&nbsp;Diego Chiappetta,&nbsp;Marcela Zubillaga","doi":"10.1186/s41181-024-00300-z","DOIUrl":"10.1186/s41181-024-00300-z","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Previous studies employing polymeric micelles and molecular imaging for in vivo nanosystem characterization have led to the development of radionanoprobes (RNPs) designed for diagnosing and monitoring therapeutic interventions in preclinical oncology research, specifically within breast and colon cancer models. These models exhibit high GLUT1 expression on tumor cells and VEGFR expression on the tumor vasculature. We aimed to enhance the tumor-targeting specificity of these RNPs by functionalizing micelles with glucose and bevacizumab. The choice of &lt;sup&gt;99m&lt;/sup&gt;Tc to label the nanoprobes is based on its availability and that direct labeling method is a widespread strategy to prepare radiopharmaceuticals using cold reagents and a &lt;sup&gt;99&lt;/sup&gt;Mo/&lt;sup&gt;99m&lt;/sup&gt;Tc generator. Soluplus&lt;sup&gt;®&lt;/sup&gt; is an attractive polymer for synthesizing micelles that also allows their functionalization. With all the above, the objective of this work was to design, develop and characterize nanoprobes based on polymeric micelles and radiolabeled with &lt;sup&gt;99m&lt;/sup&gt;Tc for the characterization of biological processes associated to the diagnosis, prognosis and monitoring of animal models of breast and colon cancer in preclinical research using molecular images.&lt;/p&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Four RNPs ([&lt;sup&gt;99m&lt;/sup&gt;Tc]Tc-Soluplus&lt;sup&gt;®&lt;/sup&gt;, [&lt;sup&gt;99m&lt;/sup&gt;Tc]Tc-Soluplus&lt;sup&gt;®&lt;/sup&gt;+TPGS, [&lt;sup&gt;99m&lt;/sup&gt;Tc]Tc-Soluplus&lt;sup&gt;®&lt;/sup&gt;+glucose and [&lt;sup&gt;99m&lt;/sup&gt;Tc]Tc-Soluplus&lt;sup&gt;®&lt;/sup&gt;+bevacizumab) were produced with high radiochemical purity (&gt; 95% in all cases) and stability in murine serum for up to 3 h. The RNPs maintained the 100 nm size of the Soluplus&lt;sup&gt;®&lt;/sup&gt; polymeric micelles even when they were functionalized and labeled with &lt;sup&gt;99m&lt;/sup&gt;Tc. The image acquisition protocol enabled the visualization of tumor uptake in two cancer experimental models using the assigned RNPs. In vivo biological characterization showed signal-to-background ratios of 1.7 ± 0.03 for [&lt;sup&gt;99m&lt;/sup&gt;Tc]Tc-Soluplus&lt;sup&gt;®&lt;/sup&gt;+TPGS, 1.8 ± 0.02 for [&lt;sup&gt;99m&lt;/sup&gt;Tc]Tc-Soluplus&lt;sup&gt;®&lt;/sup&gt;, and 2.3 ± 0.02 for [&lt;sup&gt;99m&lt;/sup&gt;Tc]Tc-Soluplus&lt;sup&gt;®&lt;/sup&gt;+glucose in the breast cancer model, and 1.8 ± 0.04 for [&lt;sup&gt;99m&lt;/sup&gt;Tc]Tc-Soluplus&lt;sup&gt;®&lt;/sup&gt; and 3.7 ± 0.07 for [&lt;sup&gt;99m&lt;/sup&gt;Tc]Tc-Soluplus&lt;sup&gt;®&lt;/sup&gt;+bevacizumab in the colon cancer model. Ex vivo biodistribution, showed that the uptake of the tumors, regardless of the model, is &lt; 2% IA/g while the blood activity concentration is higher, suggesting that the &lt;i&gt;enhanced permeability and retention&lt;/i&gt; effect (EPR) would be one of the mechanisms involved in imaging tumors in addition to the active targeting of RNPs.&lt;/p&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Soluplus&lt;sup&gt;®&lt;/sup&gt;-based polymeric micelles provide a promising nanotechnological platform for the development of RNPs. The functionalization with glucose and bevacizumab enhances tumor specificity enabling effective imaging and monitoring of cancer in animal models.&lt;","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00300-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142540757","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":"Optimized method for fluorine-18 radiolabeling of Affibody molecules using RESCA","authors":"Francesco Lechi,&nbsp;Jonas Eriksson,&nbsp;Luke R. Odell,&nbsp;Olivia Wegrzyniak,&nbsp;John Löfblom,&nbsp;Fredrik Y. Frejd,&nbsp;Bo Zhang,&nbsp;Olof Eriksson","doi":"10.1186/s41181-024-00304-9","DOIUrl":"10.1186/s41181-024-00304-9","url":null,"abstract":"<div><h3>Background</h3><p>In recent years, the interest in Al[¹⁸F]F as a labeling agent for Positron Emission Tomography (PET) radiotracers has risen, as it allows for fast and efficient fluorine-18 labeling by harnessing chelation chemistry. The introduction of Restrained Complexing Agent (RESCA) as a chelator has also shown that chelator-based radiolabeling reactions can be performed in mild conditions, making the radiolabeling process attractively more facile than most conventional radiofluorination methods. The aim of the study was to establish optimized conditions for Al[¹⁸F]F labeling of Affibody molecules using RESCA as a complexing agent, using Z₀₉₅₉₁ and Z₀₁₈₅, two Affibody proteins targeting PDGFRβ and TNFα, respectively, as model compounds.</p><h3>Results</h3><p>The Al[¹⁸F]F labeling of RESCA-conjugated Z₀₉₅₉₁ was tested at different temperatures (rt to 60 °C) and with varying reaction times (12 to 60 min), and optimal conditions were then implemented on RESCA-Z₀₁₈₅. The optimized synthesis method was: 1.5–2.5 GBq of cyclotron produced fluorine-18 were trapped on a QMA cartridge and eluted with saline solution to react with 12 nmol of AlCl₃ and form Al[¹⁸F]F. The respective RESCA-conjugated Affibody molecule (14 nmol) in NaOAc solution was added to the Al[¹⁸F]F solution and left to react at 60 °C for 12 min. The mixture was purified on a NAP5 size exclusion column and then analyzed by HPLC. The entire process took approximately 35 min, was highly reproducible, indicating the efficiency and reliability of the method. The labeled compounds demonstrated retained biological function for their respective targets after purification.</p><h3>Conclusions</h3><p>We present a general and optimized method for Al[¹⁸F]F labeling of RESCA-conjugated Affibody molecules, which can be widely applied to this class of peptide-based imaging agents. Moreover, radiochemical yields were improved when the labeling was conducted at 37 °C or above. <i>In vitro</i> and <i>in vivo</i> assessment of the respective tracers was promising, showing retained binding capacity as well as moderate defluorination, which is usually regarded as a potential downside for RESCA-conjugated tracers.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00304-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492518","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":"Sustainable production of radionuclidically pure antimony-119","authors":"Aeli P. Olson,&nbsp;Francesca A. Verich,&nbsp;Paul A. Ellison,&nbsp;Eduardo Aluicio-Sarduy,&nbsp;Robert J. Nickles,&nbsp;Jason C. Mixdorf,&nbsp;Todd E. Barnhart,&nbsp;Jonathan W. Engle","doi":"10.1186/s41181-024-00303-w","DOIUrl":"10.1186/s41181-024-00303-w","url":null,"abstract":"<div><h3>Background</h3><p>Radiopharmaceutical therapy (RPT) uses radionuclides that decay via one of three therapeutically relevant decay modes (alpha, beta, and internal conversion (IC) / Auger electron (AE) emission) to deliver short range, highly damaging radiation inside of diseased cells, maintaining localized dose distribution and sparing healthy cells. Antimony-119 (¹¹⁹Sb, t_1/2 = 38.19 h, EC = 100%) is one such IC/AE emitting radionuclide, previously limited to in silico computational investigation due to barriers in production, chemical separation, and chelation. A theranostic (therapeutic/diagnostic) pair can be formed with ¹¹⁹Sb’s radioisotopic imaging analogue ¹¹⁷Sb (t_1/2 = 2.80 h, E_γ = 158.6 keV, I_γ = 85.9%, β⁺ = 262.4 keV, I_β+ = 1.81%).</p><h3>Results</h3><p>Within, we report techniques for sustainable and cost-effective production of pre-clinical quality and quantity, radionuclidically pure ¹¹⁹Sb and ¹¹⁷Sb, novel low energy photon measurement techniques for ¹¹⁹Sb activity determination, and physical yields for various tin target isotopic enrichments and thicknesses using (p, n) and (d, n) nuclear reactions. Additionally, we present a two-column separation providing a radioantimony yield of 73.1% ± 6.9% (<i>N</i> = 3) and tin separation factor of (6.8 ± 5.5) x 10⁵ (<i>N</i> = 3). Apparent molar activity measurements for deuteron produced ¹¹⁷Sb using the chelator TREN-CAM were measured at 42.4 ± 25 MBq ¹¹⁷Sb/µmol (1.14 ± 0.68 mCi/µmol), and we recovered enriched ¹¹⁹Sn target material at a recycling efficiency of 80.2% ± 5.5% (<i>N</i> = 6) with losses of 11.6 mg ± 0.8 mg (<i>N</i> = 6) per production.</p><h3>Conclusion</h3><p>We report significant steps in overcoming barriers in ¹¹⁹Sb production, chemical isolation and purification, enriched target material recycling, and chelation, helping promote accessibility and application of this promising therapeutic radionuclide. We describe a method for ¹¹⁹Sb activity measurement using its low energy gamma (23.87 keV), negating the need for attenuation correction. Finally, we report the largest yet-measured ¹¹⁹Sb production yields using proton and deuteron irradiation of natural and enriched targets and radioisotopic purity &gt; 99.8% at end of purification.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492528","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":"First-in-human study of D6-[18F]FP-(+)-DTBZ, a novel VMAT2 tracer: whole-body biodistribution and brain PET comparison with [18F]FP-(+)-DTBZ (AV-133)","authors":"Ruiyue Zhao,&nbsp;Jinhua Chen,&nbsp;Ting Ye,&nbsp;Jianmin Chu,&nbsp;Jingwen Li,&nbsp;Yan Zhang,&nbsp;Siran Xu,&nbsp;Shaoyu Liu,&nbsp;Ling Chen,&nbsp;Karl Ploessl,&nbsp;David Alexoff,&nbsp;Hank F. Kung,&nbsp;Lin Zhu,&nbsp;Xinlu Wang","doi":"10.1186/s41181-024-00301-y","DOIUrl":"10.1186/s41181-024-00301-y","url":null,"abstract":"<div><h3>Background</h3><p>In the central nervous system, type 2 vesicular monoamine transporters (VMAT2) are responsible for the reuptake of monoamines from synaptic junction back to pre-synaptic terminal vesicles. These transporters are functionally crucial as they reflect the integrity of monoamine neurons. D6-[¹⁸F]FP-(+)-DTBZ, a novel deuterated VMAT2 radioligand, has shown promise as a potential PET tracer for the diagnosis of Parkinson’s disease (PD). This study evaluates the biodistribution and dosimetry of D6-[¹⁸F]FP-(+)-DTBZ and includes a head-to-head comparison with its non-deuterated version, [¹⁸F]FP-(+)-DTBZ (AV-133), in healthy individuals and PD patients.</p><h3>Results</h3><p>The automated synthesis of D6-[¹⁸F]FP-(+)-DTBZ using the SPE method was accomplished in 35 min, yielding a high radiochemical purity (&gt; 99%) and high radiochemical yields (35 ± 5%). The biodistribution and dosimetry study indicated an effective dose of 37.1 ± 7.2 μSv/MBq, with the liver receiving the highest radiation dose (289.6 ± 42.1 μGy/MBq), followed by pancreas (185.2 ± 29.1 μGy/MBq). Brain imaging with D6-[¹⁸F]FP-(+)-DTBZ exhibited a significantly increased uptake in VMAT2-rich regions, particularly the striatum. In a head-to-head comparison between [¹⁸F]FP-(+)-DTBZ and D6-[¹⁸F]FP-(+)-DTBZ, the latter exhibited approximately 15% higher SUVR in the caudate, putamen, and nucleus accumbens. Preliminary studies in PD patients showed a substantial reduction in VMAT2 uptake in the striatum, with the most pronounced decrease observed in the putamen (a 53% decline).</p><h3>Conclusions</h3><p>D6-[¹⁸F]FP-(+)-DTBZ is a safe and improved VMAT2-specific imaging agent, which may be suitable for diagnosing PD by evaluating changes in VMAT2 binding of monoamine neurons in the brain.</p><p><i>Trial registration</i> Chinese Clinical Trial Registry, ChiCTR2200057218, Registered 16 August 2021, https://www.chictr.org.cn/bin/project/edit?pid=142725.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00301-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443340","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":"Validation of a radiosynthesis method and a novel quality control system for [68 Ga]Ga-MAA: is TLC enough to assess radiopharmaceutical quality?","authors":"Silvia Migliari,&nbsp;Stefano Bruno,&nbsp;Annalisa Bianchera,&nbsp;Ilaria De Nardis,&nbsp;Antonio Scarano,&nbsp;Monica Lusardi,&nbsp;Anna Gaiani,&nbsp;Alessandra Guercio,&nbsp;Maura Scarlattei,&nbsp;Giorgio Baldari,&nbsp;Ruggero Bettini,&nbsp;Livia Ruffini","doi":"10.1186/s41181-024-00302-x","DOIUrl":"10.1186/s41181-024-00302-x","url":null,"abstract":"<div><h3>Background</h3><p>Technetium-99 m-labelled macroaggregated human serum albumin ([99mTc]Tc-MAA) is commonly used for lung perfusion scintigraphy. The European Pharmacopoeia (Eu.Ph.) specifies thin-layer chromatography (TLC) as the only method to assess its radiochemical purity (RCP). Similarly, TLC is the sole method reported in the literature to evaluate the RCP of Gallium-68-labelled MAA [⁶⁸ Ga]Ga-MAA, recently introduced for lung perfusion PET/CT imaging. Since [⁶⁸ Ga]Ga-MAA is prepared from commercial kits originally designed for the preparation of [99mTc]Tc-MAA, it is essential to optimize and validate the preparation methods for [⁶⁸ Ga]Ga-MAA.</p><h3>Results</h3><p>We tested a novel, simplified method for the preparation of [⁶⁸ Ga]Ga-MAA that does not require organic solvents, prewash or final purification steps to remove radioactive impurities. We assessed the final product using radio-TLC, radio-UV-HPLC, and radio SDS-PAGE. Overall, our quality control (QC) method successfully detected [⁶⁸ Ga]Ga-MAA along with all potential impurities, including free Ga-68, [⁶⁸ Ga]Ga-HSA, unlabeled HSA, which may occur during labelling process and HEPES residual, a non-toxic but non-human-approved contaminant, used as buffer solution. We then applied our QC system to [⁶⁸ Ga]Ga-MAA prepared under different conditions (25°–40°–75°–95 °C), thus defining the optimal temperature for labelling. Scanning Electron Microscopy (SEM) analysis of the products obtained through our novel method confirmed that most [⁶⁸ Ga]Ga-MAA particles preserved the morphological structure and size distribution of unlabeled MAA, with a particle diameter range of 25–50 μm, assuring diagnostic efficacy.</p><h3>Conclusions</h3><p>We optimized a novel method to prepare [⁶⁸ Ga]Ga-MAA through a QC system capable of monitoring all impurities of the final products.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00302-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438778","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":"Astatine-211 radiolabelling chemistry: from basics to advanced biological applications","authors":"Maarten Vanermen,&nbsp;Mathilde Ligeour,&nbsp;Maria-Cristina Oliveira,&nbsp;Jean-François Gestin,&nbsp;Filipe Elvas,&nbsp;Laurent Navarro,&nbsp;François Guérard","doi":"10.1186/s41181-024-00298-4","DOIUrl":"10.1186/s41181-024-00298-4","url":null,"abstract":"<div><h3>Background</h3><p>²¹¹At-radiopharmaceuticals are currently the subject of growing studies for targeted alpha therapy of cancers, which leads to the widening of the scope of the targeting vectors, from small molecules to peptides and proteins. This has prompted, during the past decade, to a renewed interest in developing novel ²¹¹At-labelling approaches and novel prosthetic groups to address the diverse scenarios and to reach improved efficiency and robustness of procedures as well as an appropriate in vivo stability of the label.</p><h3>Main body</h3><p>Translated from the well-known (radio)iodine chemistry, the long preferred electrophilic astatodemetallation using trialkylaryltin precursors is now complemented by new approaches using electrophilic or nucleophilic At. Alternatives to the astatoaryl moiety have been proposed to improve labelling stability, and the range of prosthetic groups available to label proteins has expanded.</p><h3>Conclusion</h3><p>In this report, we cover the evolution of radiolabelling chemistry, from the initial strategies developed in the late 1970’s to the most recent findings.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00298-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370582","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":"Medication reconciliation enhances the accuracy of gastric emptying scintigraphy","authors":"Vincent Nail,&nbsp;Alexandre Chapot,&nbsp;Oriane Nachar,&nbsp;Sophie Gabriel,&nbsp;Anaïs Moyon,&nbsp;David Taieb,&nbsp;Benjamin Guillet,&nbsp;Philippe Garrigue","doi":"10.1186/s41181-024-00299-3","DOIUrl":"10.1186/s41181-024-00299-3","url":null,"abstract":"<div><h3>Background</h3><p>Gastroparesis (GP) is a prevalent sensorimotor disorder characterized by delayed gastric emptying without mechanical obstruction, posing significant diagnostic challenges. Gastric emptying scintigraphy (GES) is the gold standard for diagnosing GP. However, its accuracy can be compromised by many medications that affect gastric motility. This study evaluates the impact of medication reconciliation on the diagnostic accuracy of GES.</p><h3>Results</h3><p>A significant proportion of patients (75%) were on medications known to affect gastric motility. Recommendations for medication adjustments were communicated, with 30% non-adherence. Adjustments in GES interpretations were necessary for 20% of patients following comprehensive medication reviews. The involvement of radiopharmacists facilitated accurate diagnostic conclusions, underscoring the critical role of medication reconciliation in GES accuracy.</p><h3>Conclusion</h3><p>Medication reconciliation enhanced the accuracy of GES in diagnosing gastroparesis, emphasizing the need to integrate clinical pharmacy practices into nuclear medicine. This interdisciplinary approach not only improves diagnostic accuracy but also enhances patient safety, advocating for the adoption of such practices in the management of gastroparesis.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00299-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324401","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}