Preliminary evaluation of a 18F-labeled guanidine derivative in pheochromocytoma model

Introduction: ¹⁸F-labeled radiotracers targeting norepinephrine transporter (NET) have potential applications in diagnosing and assessing several neuroendocrine tumors, especially in pheochromocytoma, paraganglioma, and neuroblastoma. In this study, we proposed a 2-step radiosynthetic method to prepare a novel guanidine-based PET tracer ¹⁸F-PhOG via organic photoredox-mediated ¹⁸F-deoxyfluorination. The diagnostic potential was evaluated in a pheochromocytoma model (PC-12).

Methods: ¹⁸F-PhOG was prepared according to modified procedures in two steps (aryl ¹⁸F-fluorination and deprotection) from a readily available precursor. PET imaging studies were performed on the PC-12 xenograft mice (n = 3) with ¹⁸F-PhOG

Results: ¹⁸F-PhOG was successfully synthesized in 35.4 ± 3.1% (n = 4) radiochemical yield and more than 97 % radiochemical purity. ¹⁸F-PhOG showed a high accumulation in the PC-12 tumor implanted in the right flank of Balb/c nude mice. The tumor uptake at 30, 60, 120, and 240 minutes after intravenous administration was 19.67±3.69, 21.05±3.57, 22.20±5.39 and 20.35±2.93. In comparison, uptake into background tissues was low and the muscle tissue uptake at 30, 60, 120, and 240 minutes was 0.41±0.08, 0.37±0.07, 0.28±0.08 and 0.24±0.06. In addition, NET-expressing tissue like brown fat and heart also showed high uptake, which supports the norepinephrine transporter (NET) targeting specificity of the ¹⁸F-PhOG. Notably, compared to the clinically used tracer ¹⁸F-MFBG, ¹⁸F-LMI1195, and other reported tracers, ¹⁸F-PhOG showed exceptionally low liver uptake. This will benefit the accurate diagnosis of potential liver metastases. The high uptake ratio of tumor to background will also promote the radiotherapy agents' development after the exchange of the F-18 to I-131 or At-211 on PhOG.

Conclusions: The novel PET radiotracer ¹⁸F-PhOG demonstrated favorable biodistribution in pheochromocytoma model. The preliminary PET imaging results suggest the potential usefulness of ¹⁸F-PhOG as a diagnostic agent for the of NET–expressing tumors.

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