A Review on the Current State and Future Perspectives of [99mTc]Tc-Housed PSMA-i in Prostate Cancer

Recently, prostate-specific membrane antigen (PSMA) has gained momentum in tumor nuclear molecular imaging as an excellent target for both the diagnosis and therapy of prostate cancer. Since 2008, after years of preclinical research efforts, a plentitude of radiolabeled compounds mainly based on low molecular weight PSMA inhibitors (PSMA-i) have been described for imaging and theranostic applications, and some of them have been transferred to the clinic. Most of these compounds include radiometals (e.g., Ga-68, Cu-64, Lu-177) for positron emission tomography (PET) imaging or endoradiotherapy. Nowadays, although the development of new PET tracers has caused a significant drop in single-photon emission tomography (SPECT) research programs and the development of new technetium-99m (Tc-99m) tracers is rare, this radionuclide remains the best atom for SPECT imaging owing to its ideal physical decay properties, convenient availability, and rich and versatile coordination chemistry. Indeed, Tc-99m still plays a relevant role in diagnostic nuclear medicine, as the number of clinical examinations based on Tc-99m outscores that of PET agents and Tc-99m-PSMA SPECT/CT may be a cost-effective alternative for Ga-68-PSMA PET/CT. This review aims to give an overview of the specific features of the developed [Tc-99m]Tc-tagged PSMA agents with particular attention to [Tc-99m]Tc-PSMA-i. The chemical and pharmacological properties of the latter will be compared and discussed, highlighting the pros and cons with respect to [Ga-68]Ga-PSMA11.

Automated summary

Prostate-specific membrane antigen (PSMA) has been proven to be an excellent target for diagnosis and therapy of prostate cancer. Radiolabeled compounds based on low molecular weight PSMA inhibitors have been developed for tumor nuclear molecular imaging. Technetium-99m (Tc-99m) remains the best option for single-photon emission tomography (SPECT) imaging, despite the development of new PET tracers.