Enhanced pre-therapy dosimetry for SSTR PET: A head-to-head preclinical assessment of [⁸⁹Zr]Zr-DFO-TOC and [⁸⁹Zr]Zr-DFO-TATE.

Abstract

Neuroendocrine tumors (NETs) represent a clinically heterogeneous group of malignancies originating from neuroendocrine cells, with the potential to arise in nearly any organ system. Despite their relatively low incidence, NETS are associated with significant morbidity and mortality, with reported 1- and 5-year mortality rate of 27.2% and 60.4%, respectively. These statistics underscore the critical importance of early and accurate diagnosis. A hallmark of NET biology is the overexpression of somatostatin receptors (SSTRs) on NET cell membranes. This molecular feature has been effectively exploited for both imaging and through the use of radiolabeled somatostatin analogues. To date, three FDA-approved radiopharmaceuticals for PET imaging of somatostatin receptor positive (SSTR+) NETs are clinically available, establishing PET as the standard imaging modality for disease detection, staging, and treatment planning of NETs. However, current tracers are limited by either the short half-lives or by practical constraints in production and distribution, restricting their broader clinical utility. ⁸⁹Zr (t1/2 = 3.27 days, β+ = 22.3%, β+avg = 395.5 keV) offers an attractive alternative, enabling imaging at extended timepoints with improved tumor-to-background contrast and the potential for more accurate pretherapy dosimetry. The aim of this work is to evaluate [⁸⁹Zr]Zr-DFO-TATE and [⁸⁹Zr]Zr-DFO-TOC for PET imaging of SSTR+ NETs. This study seeks to provide a comprehensive in vivo comparison of the two agents including the in vivo PET imaging, ex vivo biodistribution, and internal radiation dosimetry, with the overarching goal of advancing precision diagnostics and improving therapeutic planning for NET patients undergoing [¹⁷⁷Lu]Lu-DOTA-TATE therapy.