Synthesis, radiolabeling, and pre-clinical evaluation of [44Sc]Sc-AAZTA conjugate PSMA inhibitor, a new tracer for high-efficiency imaging of prostate cancer

• Published in: European journal of nuclear medicine and molecular imaging Vol. 48; no. 8; pp. 2351 - 2362
• Main Authors: Ghiani, S., Hawala, I., Szikra, D., Trencsényi, G., Baranyai, Z., Nagy, G., Vágner, A., Stefania, R., Pandey, S., Maiocchi, A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2021; Springer Nature B.V
• Subjects: Accumulation; Animals; Blood plasma; Calcium; Cardiology; Cell Line, Tumor; Chelating agents; Chemical synthesis; Cyclotrons; Gadolinium; Glutamate Carboxypeptidase II - metabolism; Humans; Imaging; In vivo methods and tests; Inhibitors; Magnetic resonance imaging; Male; Medical imaging; Medicine; Medicine & Public Health; Mice; Nuclear Medicine; Oncology; Original Article; Orthopedics; Peptide synthesis; Positron emission; Positron emission tomography; Preclinical Imaging; Prostate cancer; Prostatic Neoplasms - diagnostic imaging; Radioactive labeling; Radiochemistry; Radioisotopes; Radiolabelling; Radiology; Radiopharmaceuticals; Room temperature; Scandium; Solid phases; Tissue Distribution; Tomography; Tumors; Scandium-44; PET/MRI; AAZTA; Prostate-specific membrane antigen (PSMA)–targeted radioligand
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-020-05130-0

Purpose The aim of this work was to demonstrate the suitability of AAZTA conjugated to PSMA inhibitor (B28110) labeled with scandium-44 as a new PET tracer for diagnostic imaging of prostate cancer. Background Nowadays, scandium-44 has received significant attention as a potential radionuclide with favorable characteristics for PET applications. A polyaminopolycarboxylate heptadentate ligand based on a 1,4-diazepine scaffold (AAZTA) has been thoroughly studied as chelator for Gd 3+ ions for MRI applications. The excellent results of the equilibrium, kinetic, and labeling studies led to a preliminary assessment of the in vitro and in vivo behavior of [ 44 Sc][Sc-(AAZTA)] − and two derivatives, i.e., [ 44 Sc][Sc (CNAAZTA-BSA)] and [ 44 Sc][Sc (CNAAZTA-cRGDfK)]. Results B28110 was synthesized by hybrid approach, combining solid-phase peptide synthesis (SPPS) and solution chemistry to obtain high purity (97%) product with an overall yield of 9%. Subsequently, the radioactive labeling was performed with scandium-44 produced from natural calcium target in cyclotron, in good radiochemical yields (RCY) under mild condition (pH 4, 298 K). Stability study in human plasma showed good RCP% of [ 44 Sc]Sc-B28110 up to 24 h (94.32%). In vivo PET/MRI imaging on LNCaP tumor-bearing mice showed high tracer accumulation in the tumor regions as early as 20 min post-injection. Ex vivo biodistribution studies confirmed that the accumulation of 44 Sc-PSMA-617 was two-fold lower than that of the radiolabeled B28110 probes. Conclusions This work demonstrated the suitability of B28110 for the complexation with scandium-44 at room temperature and the high performance of the resulting new tracer based on AAZTA chelator for the diagnosis of prostate cancer using PET.