Human gastrin- releasing peptide receptor expression in women with uterine cervix cancer.

Abstract

212Pb-DOTAM-GRPR1 is a pharmaceutical radioimmunoconjugate consisiting of an α-particle-emitting radionuclide lead-212 (212Pb), a metal chelator DOTAM (1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane), and a gastrin-releasing peptide receptor (GRPR)-targeted antagonist currently being evaluated as therapy in uterine cervix and other cancer types. Previous studies have revealed that a variable proportion of uterine cervix cancer tumors overexpress the radiopharmaceutical target GRPR when assessed by cell proportion and staining intensity immunoreactive scores (IRS). Tumor response to 212Pb-DOTAM-GRPR1 strongly associates with GRPR overexpression, and therefore, it seems reasonable to assess uterine cervix cancer GRPR immunoreactivity for greater insight into the feasibility of using 212Pb-DOTAM-GRPR1 as a radiopharmaceutical treatment. We examined a series of 33 uterine cervix cancer paraffin-embedded tumors in order to establish whether this tumor type overexpresses GRPR at an IRS score of 6 or higher, as 212Pb-DOTAM-GRPR1 is currently being evaluated in clinical trials against tumors showing such a level of expression. The results show that five of five (100%) primary adenocarcinomas and 10 of 16 (63%) primary squamous cell tumors overexpress GRPR at an IRS score of 6 or higher. The frequency of overexpression in this study suggests that 212Pb-DOTAM-GRPR1 radiopharmaceutical treatment may be useful in the management of persistent, recurrent, or metastatic uterine cervix cancer patients. A phase I clinical trial involving patients with metastatic uterine cervix cancer is currently underway (NCT05283330).