Comparison of Prostate-Specific Membrane Antigen Expression Levels in Human Salivary Glands to Non-Human Primates and Rodents

Abstract

<b><i>Background:</i></b> Prostate-specific membrane antigen (PSMA) has emerged as a promising target for developing radionuclide therapy (RNT) in prostate cancer; however, accumulation of PSMA-RNT in salivary glands can result in irreversible xerostomia. Methods to prevent PSMA-RNT-related xerostomia could be clinically useful; however, little is known about PSMA expression in salivary glands of preclinical animal models. Using [¹⁸F]DCFPyL autoradiography/biodistribution, PSMA expression levels were determined in salivary glands of various preclinical monkey and rodent species and compared with humans. <b><i>Methods:</i></b> Binding affinities (K_d) and PSMA levels (B_max) were determined by <i>in vitro</i> [¹⁸F]DCFPyL autoradiography studies. <i>In vivo</i> rodent tissue uptakes (%ID/g) were determined from [¹⁸F]DCFPyL biodistributions. <b><i>Results:</i></b> [¹⁸F]DCFPyL exhibited low nanomolar K_d for submandibular gland (SMG) PSMA across all the species. PSMA levels in human SMG (B_max = 60.91 nM) were approximately two-fold lower compared with baboon SMG but were two- to three-fold higher than SMG PSMA levels of cynomolgus and rhesus. Rodents had the lowest SMG PSMA levels, with the mouse being 10-fold higher than the rat. <i>In vivo</i> rodent biodistribution studies confirmed these results. <b><i>Conclusions:</i></b> SMG of monkeys exhibited comparable PSMA expression to human SMG whereas rodents were lower. However, the results suggest that mice are relatively a better small animal preclinical model than rats for PSMA salivary gland studies.