Abstract
2721a
Objectives The sodium/iodide symporter (NIS) is under investigation as a reporter for noninvasive imaging of gene expression. Although [18F]tetrafluoroborate ([18F]TFB, [18F]BF4-) has shown promise as a PET imaging probe for NIS, the current synthesis method employing isotopic exchange gives suboptimal radiochemical yield and specific activity. The aim of this study was to synthesize [18F] TFB via direct radiofluorination on boron trifluoride (BF3) to enhance both labeling yield and specific activity, and evaluation of specific activity influence on tumor uptake.
Methods An automated synthesis of [18F]TFB was developed whereby cyclotron-produced [18F]fluoride was trapped on a quaternary methyl ammonium anion exchange (QMA) cartridge, then allowed to react with BF3 freshly pre-formulated in petroleum ether / tetrahydrofuran (THF) (50:1). The resultant [18F]TFB product was retained on the QMA cartridge. After rinsing the cartridge with THF and water, [18F]TFB was eluted from the cartridge with isotonic saline, passing through two neutral alumina cartridges and a sterilizing filter. Preclinical imaging studies with [18F]TFB were performed in athymic mice bearing NIS-expressing C6 glioma subcutaneous xenografted tumors to determine influence of specific activity on tumor uptake.
Results Under optimized conditions, [18F]TFB was synthesized in radiochemical yield of 20.0 ± 0.7% (n = 3, uncorrected for decay) and >98% radiochemical purity in a synthesis time of 10 min. Specific activities of 8.84 ± 0.56 GBq/µmol (n = 3) were achieved from starting [18F]fluoride radioactivities of 40-44 GBq. An avid uptake of [18F]TFB was observed in human NIS (hNIS) expressing C6 glioma xenografts as well as expected NIS-mediated uptake in thyroid and NIS-/choline transporter- mediated uptake in stomach. There was a positive correlation between the uptake of [18F]TFB in hNIS-expressing tumor and specific activity.
Conclusions A rapid, practical, and high-specific activity synthesis of the NIS reporter probe [18F]TFB was achieved via direct radiofluorination on BF3 using an automated synthesis system. Preclinical evaluation studies in C6-glioma bearing mice showed robust uptake of [18F]TFB in hNIS-expressing tumors. This synthesis with high specific activity [18F]TFB should enable future clinical studies with NIS gene reporter viral constructs and avoid pharmacological effects. Figure 1. PET images of [18F]TFB distribution in control mouse (left) and a mouse bearing hNIS-positive and hNIS-negative C6 glioma xenografts. The overlaid reference bone atlas is computer generated.