Targeting prostate cancer with the anti-PSMA scFvD2B: a theranostic promise for nuclear medicine

Introduction: Despite the significant research activity in the design and validation of new PSMA-targeting agents, prostate cancer (PCa) remains the second most common cancer in men worldwide. PSMA-specific labeled monoclonal antibodies (mAbs) demonstrated a discrete effectiveness in the clinic, but with some drawbacks due to their large size. To circumvent these problems, mAbs-derived fragments have been investigated, since they retain the high affinity of the parent mAb for the target, being also endowed with a more favorable pharmacokinetics. This review focuses on the single-chain variable fragment D2B (scFvD2B) potentiality as a new prostate-specific membrane antigen (PSMA)-specific molecular vector in nuclear medicine (NM) applications for both diagnosis and treatment of PCa. Methods: A critical review of PubMed and Web of Science (including MEDLINE) in the early 2019 was performed, searching for research articles focusing on the application of the fragment scFvD2B and the parent antibody IgGD2B in preclinical NM. Results: The scFvD2B, which is derived from one of the most promising PSMA-specific mAbs, IgGD2B, has been recently investigated and labeled with Indium-111, Iodine-131, and Iodine-123. Overall, scFvD2B showed a great potential in the preclinical setting, demonstrating a promising pharmacokinetics, especially in terms of high stability and specificity, efficiently accumulating in PSMA-expressing PCa tumors. Conclusion: scFvD2B seems to be a promising fragment as a molecular vector in NM applications. Nevertheless, further investigations, especially with radiometal-labeled scFvD2B, are necessary to better characterize and optimize the unique properties of this fragment, providing the basis for a rapid translation into the clinic.