Synthesis and Preclinical Evaluation of Folate-NOTA-Al18F for PET Imaging of Folate Receptor-Positive Tumors

摘要

Folate receptor-targeted PET radiotracers can potentially serve as versatile imaging agents for the diagnosis, staging, and prediction of response to therapy of patients with folate receptor (FR)-expressing cancers. Because current FR-targeted PET reagents can be compromised by complex labeling procedures, low specific activities, poor radiochemical yields or unwanted accumulation in FR negative tissues, we have undertaken to design an improved folate-PET agent that might be more amenable for clinical development. For this purpose, we have synthesized a folate-NOTAAl¹⁸F radiotracer and examined its properties both in vitro and in vivo.MethodsRadiochemical synthesis of folate-NOTA-Al¹⁸F was achieved by incubating ¹⁸F⁻ with AlCl3 for 2 min followed by heating in the presence of folate-NOTA for 15 min at 100 °C. Binding of folate-NOTA-Al¹⁸F to FR was quantitated in homogenates of KB and Cal51 tumor xenografts in the presence and absence of excess folic acid as a competitor. In vivo imaging was performed on nuu mice bearing either FR+ve (KB cell) or FR−ve (A549 cell) tumor xenografts, and specific accumulation of the radiotracer in tumor and other tissues was assessed by high-resolution micro-PET and ex vivo biodistribution in the presence and absence of excess folic acid. Image quality of folate-NOTA-Al¹⁸F was compared with that of ^99mTc-EC20, a clinically established folate-targeted SPECT imaging agent.