Open AccessComparison of Prostate-Specific Membrane Antigen Expression Levels in Human Salivary Glands to Non-Human Primates and Rodents
Author(s) -
Jyoti Roy,
Blake M. Warner,
Falguni Basuli,
Xiang Zhang,
Karen Wong,
Thomas Pranzatelli,
Anita Ton,
John A. Chiorini,
Peter L. Choyke,
Frank I. Lin,
Elaine M. Jagoda
Publication year - 2020
Publication title -
cancer biotherapy and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.716
H-Index - 59
eISSN - 1557-8852
pISSN - 1084-9785
DOI - 10.1089/cbr.2019.3079
Subject(s) - biodistribution , baboon , salivary gland , in vivo , in vitro , rodent , saliva , submandibular gland , immunohistochemistry , pathology , antigen , biology , medicine , microbiology and biotechnology , endocrinology , immunology , biochemistry , ecology
Background: 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 [ 18 F]DCFPyL autoradiography/biodistribution, PSMA expression levels were determined in salivary glands of various preclinical monkey and rodent species and compared with humans. Methods: Binding affinities (K d ) and PSMA levels (B max ) were determined by in vitro [ 18 F]DCFPyL autoradiography studies. In vivo rodent tissue uptakes (%ID/g) were determined from [ 18 F]DCFPyL biodistributions. Results: [ 18 F]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. In vivo rodent biodistribution studies confirmed these results. Conclusions: 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.