Comparison Study of [18F]FAl-NOTA-PRGD2, [18F]FPPRGD2, and [68Ga]Ga-NOTA-PRGD2 for PET Imaging of U87MG Tumors in Mice

Abstract

[¹⁸F]FPPRGD2, an F-18 labeled dimeric cyclic RGDyK peptide, has favorable properties for PET imaging of angiogenesis by targeting the α_vβ₃ integrin receptor. This radiotracer has been approved by the FDA for use in clinical trials. However, the time-consuming multiple-step synthetic procedure required for its preparation may hinder the widespread usage of this tracer. The recent development of a method using an F-18 fluoride-aluminum complex to radiolabel peptides provides a strategy for simplifying the labeling procedure. On the other hand, the easy-to-prepare [⁶⁸Ga]-labeled NOTA-RGD derivatives have also been reported to have promising properties for imaging α_vβ₃ integrin receptors. The purpose of this study was to prepare [¹⁸F]FPPRDG2, [¹⁸F]FAl-NOTA-PRGD2, and [⁶⁸Ga]Ga-NOTA-PRGD2 and to compare their pharmacokinetics and tumor imaging properties using small animal PET. All three compounds showed rapid and high tracer uptake in U87MG tumors with high target-to-background ratios. The uptake in the liver, kidneys, and muscle were similar for all three tracers, and they all showed predominant renal clearance. In conclusion, [¹⁸F]FAl-NOTA-PRGD2 and [⁶⁸Ga]Ga-NOTA-PRGD2 have imaging properties and pharmacokinetics comparable to those of [¹⁸F]FPPRGD2. Considering their ease of preparation and good imaging qualities, [¹⁸F]FAl-NOTA-PRGD2 and [⁶⁸Ga]NOTA-PRGD2 are promising alternatives to [¹⁸F]FPPRGD2 for PET imaging of tumor α_vβ₃ integrin expression.