IntroductionHigh-risk human epidermal growth factor receptor 2 (HER2)-positive adenocarcinomas associate with early recurrence and death, prompting consideration of novel radiotherapeutic options like a trastuzumab-linked thorium-227 alpha-particle emitting radionuclide.MethodsWe conducted a retrospective pilot biomarker study of uterine cervix cancers among patients in Appalachian Kentucky, to characterize an exploitable triage biomarker like HER2 expression before starting a prospective phase 0 trial.ResultsMost (60%) adenocarcinomas showed HER2 cell-surface overexpression, whereas squamous cell carcinomas (4%) did not do so.DiscussionFurther validation tests of HER2 expression as a triage biomarker for radiopharmaceutical selection are warranted.

Introduction212Pb-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.MethodsWe 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.ResultsThe 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.DiscussionThe 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).