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The GRPR Antagonist [Tc-99m]Tc-maSSS-PEG(2)-RM26 towards Phase I Clinical Trial: Kit Preparation, Characterization and Toxicity
Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.ORCID iD: 0000-0002-1793-6062
Uppsala Univ, Dept Med Chem, S-75183 Uppsala, Sweden..
Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Med, Tomsk 634009, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk 634050, Russia..
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2023 (English)In: Diagnostics, ISSN 2075-4418, Vol. 13, no 9, p. 1611-, article id 1611Article in journal (Refereed) Published
Abstract [en]

Gastrin-releasing peptide receptors (GRPRs) are overexpressed in the majority of primary prostate tumors and in prostatic lymph node and bone metastases. Several GRPR antagonists were developed for SPECT and PET imaging of prostate cancer. We previously reported a preclinical evaluation of the GRPR antagonist [Tc-99m]Tc-maSSS-PEG2-RM26 (based on [D-Phe(6), Sta(13), Leu(14)-NH2]BBN(6-14)) which bound to GRPR with high affinity and had a favorable biodistribution profile in tumor-bearing animal models. In this study, we aimed to prepare and test kits for prospective use in an early-phase clinical study. The kits were prepared to allow for a one-pot single-step radiolabeling with technetium-99m pertechnetate. The kit vials were tested for sterility and labeling efficacy. The radiolabeled by using the kit GRPR antagonist was evaluated in vitro for binding specificity to GRPR on PC-3 cells (GRPR-positive). In vivo, the toxicity of the kit constituents was evaluated in rats. The labeling efficacy of the kits stored at 4 degrees C was monitored for 18 months. The biological properties of [Tc-99m]Tc-maSSS-PEG2-RM26, which were obtained after this period, were examined both in vitro and in vivo. The one-pot (gluconic acid, ethylenediaminetetraacetic acid, stannous chloride, and maSSS-PEG(2)-RM26) single-step radiolabeling with technetium-99m was successful with high radiochemical yields (>97%) and high molar activities (16-24 MBq/nmol). The radiolabeled peptide maintained its binding properties to GRPR. The kit constituents were sterile and non-toxic when tested in living subjects. In conclusion, the prepared kit is considered safe in animal models and can be further evaluated for use in clinics.

Place, publisher, year, edition, pages
MDPI AG , 2023. Vol. 13, no 9, p. 1611-, article id 1611
Keywords [en]
prostate cancer, GRPR antagonist, technetium-99m, sterility, toxicity testing
National Category
Cancer and Oncology Medical Laboratory and Measurements Technologies
Identifiers
URN: urn:nbn:se:kth:diva-329884DOI: 10.3390/diagnostics13091611ISI: 000987259800001PubMedID: 37175001Scopus ID: 2-s2.0-85159164864OAI: oai:DiVA.org:kth-329884DiVA, id: diva2:1774511
Note

QC 20230626

Available from: 2023-06-26 Created: 2023-06-26 Last updated: 2023-06-26Bibliographically approved

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Borin, JesperHober, Sophia

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