EJNMMI Radiopharmacy and Chemistry最新文献

{"title":"Lead-it-EAZY! GMP-compliant production of [212Pb]Pb-PSC-PEG2-TOC","authors":"Marc Pretze,&nbsp;Enrico Michler,&nbsp;David Kästner,&nbsp;Falk Kunkel,&nbsp;Edwin A. Sagastume,&nbsp;Michael K. Schultz,&nbsp;Jörg Kotzerke","doi":"10.1186/s41181-024-00305-8","DOIUrl":"10.1186/s41181-024-00305-8","url":null,"abstract":"<div><h3>Background</h3><p>Recently, radiotheranostics comprising the true matched radionuclide pair ^203/212Pb could serve as real dosimetric planning utility using ²⁰³Pb-radiolabelled pharmaceuticals before therapy with ²¹²Pb-radiolabelled counterparts. ²¹²Pb might act as the missing radionuclide therapy between standard β^– therapies (e.g. with ¹⁷⁷Lu or ⁹⁰Y), in some cases leading to β^– resistance and highly cytotoxic α therapies (e.g. with ²²⁵Ac) leading in some cases to renal insufficiency or even renal failure, due to the daughter nuclide ²¹³Bi, which accumulates in &gt; 90% within the kidneys during ²²⁵Ac therapy. ²¹²Pb converts to ²¹²Bi by β^–-decay and the following pathway of decay bears in sum only one α decay, which certainly happens within the targeted tumour tissue. Following daughter nuclides (e.g. ²⁰⁸Tl), which could distribute in organs at risk have only β⁻ or γ decay, which is not as cytotoxic as α decay.</p><h3>Results</h3><p>By ingenious customization of the standard cassettes of the ML EAZY it was possible to adapt the manual radiosynthesis of [²¹²Pb]Pb-PSC-PEG₂-TOC ([²¹²Pb]Pb-VMT-α-NET) to a GMP-compliant synthesis module. The whole process of production, namely conditioning of C18 cartridge for purification, elution of the ²²⁴Ra/²¹²Pb-generator, radiolabelling, C18 purification and sterile filtration performed automatically within one hour to access [²¹²Pb]Pb-VMT-α-NET for patient application. [²¹²Pb]Pb-VMT-α-NET was radiolabelled with high radiochemical purity &gt; 95% and high radiochemical yield &gt; 95% with molar activity ~ 15.8 MBq/nmol.</p><h3>Conclusions</h3><p>The Lead-it-EAZY process performed stable and robust over ten radiosyntheses and yielded sterile [²¹²Pb]Pb-VMT-α-NET in high purity for patient application. By changing the precursor this process could easily be adapted to other ²¹²Pb-radiopharmaceuticals.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00305-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737091","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":"SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG mice","authors":"Nasim Sarrami,&nbsp;Bryce Nelson,&nbsp;Samantha Leier,&nbsp;John Wilson,&nbsp;Conrad Chan,&nbsp;Jalna Meens,&nbsp;Teesha Komal,&nbsp;Laurie Ailles,&nbsp;Melinda Wuest,&nbsp;Michael Schultz,&nbsp;Afsaneh Lavasanifar,&nbsp;Raymond M. Reilly,&nbsp;Frank Wuest","doi":"10.1186/s41181-024-00313-8","DOIUrl":"10.1186/s41181-024-00313-8","url":null,"abstract":"<div><h3>Background</h3><p>The objective of this research was the development and evaluation of ²⁰³Pb-labelled panitumumab (²⁰³Pb-PSC-panitumumab) as an immuno-SPECT radioligand for the detection of EGFR + head and neck squamous cell carcinoma (HNSCC) in a patient-derived xenograft (PDX) mouse model<i>.</i> The 51.9 h physical half-life and favourable γ-emission (279 keV; 81%) of ²⁰³Pb offer an excellent opportunity for developing immuno-SPECT radioligands. Moreover, ²⁰³Pb has a complementary therapeutic radionuclide (²¹²Pb), making ²⁰³Pb and ²¹²Pb an ideal matched radiotheranostic pair.</p><h3>Results</h3><p>Radiolabeling of panitumumab was performed at a pH of 5.0 and room temperature for 5–10 min with [²⁰³Pb]Pb(OAc)₂, and the incorporation efficiency was determined using radio-TLC. ²⁰³Pb-PSC-panitumumab (~ 10 MBq, 140 μl of saline) was injected into the tail vein of NRG mice bearing subcutaneous (s.c.) HNSCC patient-derived xenografts (PDX). SPECT/CT images were acquired at 48 and 120 h post-injection. For biodistribution studies, mice were euthanized five days after ²⁰³Pb-panitumumab injection. The tumour and normal tissues were collected and weighed, and uptake of ²⁰³Pb was measured in a γ-counter. The uptake was calculated as the percent injected dose per gram of each tissue (ID%/g). Blocking experiments were performed by pretreating a group of mice (n = 5) with 1 mg of panitumumab 1 h before administering ²⁰³Pb-PSC-panitumumab. 4–5 chelators of a new lead-specific chelator (PSC) were attached per antibody; radiolabeling efficiency was 99.2 ± 0.7%. The isolated radiochemical yield of ²⁰³Pb-PSC-panitumumab was 41.4 ± 8% (n = 5), and the molar activity was 1.2 ± 0.35 GB/mg. SPECT imaging and biodistribution confirmed high accumulation and retention of ²⁰³Pb-PSC-panitumumab in the tumour (26% ID/g) at 120 h post-injection (p.i.), which could be reduced to 6.2%ID/g at 120 h p.i. by predosing with panitumumab (1 mg) confirming EGFR specificity of ²⁰³Pb-PSC-panitumumab uptake.</p><h3>Conclusions</h3><p>Panitumumab was successfully and reproducibly labelled with ²⁰³Pb in high radiochemical purity using the chelator PSC-NCS. ²⁰³Pb-PSC-panitumumab was specifically accumulated and retained in EGFR + tumours in NRG mice with s.c. HNSCC PDX. ²⁰³Pb-PSC-panitumumab is a suitable immuno-SPECT radioligand for imaging EGFR + tumours and has great potential for combining with ²¹²Pb-PSC-panitumumab in a radiotheranostic strategy for imaging and treating HNSCC.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00313-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714259","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":"Preclinical evaluation and automated synthesis of [89Zr]ZrDFOSquaramide-girentuximab for diagnostic imaging of carbonic anhydrase IX positive tumours","authors":"Asif Noor,&nbsp;Emily R. McGowan,&nbsp;Jessica K. Van Zuylekom,&nbsp;Carleen Cullinane,&nbsp;Peter D. Roselt,&nbsp;Rodney J. Hicks,&nbsp;Michael P. Wheatcroft,&nbsp;Paul S. Donnelly","doi":"10.1186/s41181-024-00310-x","DOIUrl":"10.1186/s41181-024-00310-x","url":null,"abstract":"<div><h3>Background</h3><p>Carbonic Anhydrase IX (CAIX) is a zinc metalloenzyme that is over-expressed in many cancers making it a valid target for targeted diagnostic imaging with Positron Emission Tomography (PET). The monoclonal antibody girentuximab binds to CAIX and when radiolabelled with positron-emitting zirconium-89 can be used for diagnostic PET imaging of CAIX positive tumours.</p><h3>Results</h3><p>Reaction of desferrioxamine squaramide ethyl ester with girentuximab allowed isolation of a conjugate with desferrioxamine squaramide (DFOSq) covalently attached to girentuximab through stable vinylogous amide linkages to give DFOSq-girentuximab. This conjugate was radiolabelled with zirconium-89 to give [⁸⁹Zr]ZrDFOSq-girentuximab and the tumour uptake of the tracer was evaluated in CAIX positive HT29 tumour-bearing mice. Analysis of the PET images and biodistribution studies showed that the tracer displays high tumour uptake. An automated process for production of [⁸⁹Zr]ZrDFOSq-girentuximab was developed, using [⁸⁹Zr]ZrCl₄ as a starting material that was also synthesized in an automated process. This automated process allows isolation of [⁸⁹Zr]ZrDFOSq-girentuximab in radiochemical yields of 80–90% and in &gt; 95% radiochemical purity.</p><h3>Conclusions</h3><p>[⁸⁹Zr]ZrDFOSq-girentuximab has high uptake in CAIX positive tumours. An automated procedure for the synthesis of [⁸⁹Zr]ZrDFOSq-girentuximab using [⁸⁹Zr]ZrCl₄ as a starting material has been developed. This automated process could be readily adapted to other antibodies.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00310-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714344","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":"Numerical simulation method for the assessment of the effect of molar activity on the pharmacokinetics of radioligands in small animals","authors":"Tatsuya Kikuchi,&nbsp;Toshimitsu Okamura,&nbsp;Ming-Rong Zhang","doi":"10.1186/s41181-024-00308-5","DOIUrl":"10.1186/s41181-024-00308-5","url":null,"abstract":"<div><h3>Background</h3><p>It is well recognized that the molar activity of a radioligand is an important pharmacokinetic parameter, especially in positron emission tomography (PET) of small animals. Occupation of a significant number of binding sites by radioligand molecules results in low radioligand accumulation in a target region (mass effect). Nevertheless, small-animal PET studies have often been performed without consideration of the molar activity or molar dose of radioligands. A simulation study would therefore help to assess the importance of the mass effect in small-animal PET. Here, we introduce a new compartmental model-based numerical method, which runs on commonly used spreadsheet software, to simulate the effect of molar activity or molar dose on the pharmacokinetics of radioligands.</p><h3>Results</h3><p>Assuming a two-tissue compartmental model, time-concentration curves of a radioligand were generated using four simulation methods and the well-known Runge–Kutta numerical method. The values were compared with theoretical values obtained under an ultra-high molar activity condition (pseudo-first-order binding kinetics), a steady-state condition and an equilibrium condition (second-order binding kinetics). For all conditions, the simulation method using the simplest calculation yielded values closest to the theoretical values and comparable with those obtained using the Runge–Kutta method. To satisfy a maximum occupancy less than 5%, simulations showed that a molar activity greater than 150 GBq/μmol is required for a model radioligand when 20 MBq is administered to a 250 g rat and when the concentration of binding sites in target regions is greater than 1.25 nM.</p><h3>Conclusions</h3><p>The simulation method used in this study is based on a very simple calculation and runs on widely used spreadsheet software. Therefore, simulation of radioligand pharmacokinetics using this method can be performed on a personal computer and help to assess the importance of the mass effect in small-animal PET. This simulation method also enables the generation of a model time-activity curve for the evaluation of kinetic analysis methods.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00308-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142679700","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 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}