Neuroendocrine tumors (NETs) are a class of neoplasms originating from neuroendocrine cells that can arise anywhere in the body. Each year, ~12,000 people are diagnosed with NETs in the U.S. The 1- and 5-year mortality rates for patients are ~27.2% and 60.4%, respectively, highlighting the need for early diagnosis. Somatostatin receptor 2 (SSTR2) is frequently overexpressed on the surface of NETs, making it an excellent target for the development of receptor specific agents. Positron Emission Tomography (PET) is underway as a leading diagnostic tool with the recent approvals of three positron emitting radiopharmaceuticals for SSTR+ NETs. This work aims to test the in vivo stability of two zirconium-89 (⁸⁹Zr) chelators, deferoxamine (DFO) and tetraxetan (DOTA), conjugated with the long-lived somatostatin analogue, octreotide (TOC). ⁸⁹Zr is a promising radionuclide for the development of PET tracers, due to its favorable nuclear characteristics (t_½ = 3.27 days, β⁺ = 22.3%, β_avg= 395.5 keV) and chemical characteristics (+4 oxidation state, preferential coordination number of 7/8, and favorable aqueous chemistry). ⁸⁹Zr-DFO-TOC and ⁸⁹Zr-DOTA-TOC will leverage these excellent characteristics and dissect the in vivo stability of the chelators, DFO and DOTA, in hopes of developing a novel radiopharmaceutical for improved PET imaging of SSTR+ NETS at longer timepoints. Our aim is to determine the suitability in detecting and diagnosing SSTR+ NETs with ⁸⁹Zr probes. Using ⁸⁹Zr will also allow for dosimetry information pertinent for future theragnostic applications with long-lived therapeutic radionuclides, such as ¹⁷⁷Lu. If successful, this work will demonstrate the ability to utilize the excellent nuclear and chemical properties of ⁸⁹Zr for sensitive detection and diagnoses of SSTR+ NETs, while giving insight into the preferential coordination complex formed by ⁸⁹Zr during radiolabeling. This work has the potential to greatly impact patient care through the possibility of earlier detection and improved NET diagnoses.

Alexis Sanwick

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