Radiosynthesis and radiopharmacological charakterization of n.c.a. sodium [¹⁸f]fluoroacetate in tumor bearing mice

Introduction:

[18F]Fluoroacetate is discussed as an alternative to the well-established PET radiotracer [11C]acetate for the diagnosis and treatment monitoring of prostate cancer. The first automated synthesis of [18F]fluoroacetate was reported very recently by Sun and co-workers [1]. Herein we describe an alternative convenient remotely-controlled synthesis of no-carrier-added sodium [18F]fluoroacetate and its radiopharmacological evaluation in tumor bearing mice.

Experimental:

Three ethyl esters and three tert.-butyl esters containing either a methanesulfonyloxy- (OMs), p-toluenesulfonyloxy- (OTs) or p-nitrobenzene-sulfonyloxy (ONs) leaving group were investigated as labeling precursors.

Results and Discussion:

The optimized radiosynthesis of n.c.a. sodium [18F]fluoroacetate was performed in two steps: (1) Incorporation of fluorine into (methanesulfonyloxy)-acetic acid tert.-butyl ester 1 as the superior labeling precursor in acetonitrile at 100°C for 5 min followed by (2) acidic hydrolysis of the resulting [18F]fluoroacetic acid tert.-butyl ester at 100°C for 10 min to afford [18F]fluoroacetic acid. Several consecutive purification steps using anion exchange cartridges (Alltech Maxi-Clean SAX) and Sep-Pak neutral alumina cartridges gave sodium [18F]fluoroacetate in very reproducible radiochemical yields (20-25%, decay-corrected, n=20) in high radiochemical purity (>95%) within 50 min (Fig. 1).
Radiopharmacological studies were performed using rats and tumor bearing mice. Metabolism studies in arterial blood showed no metabolites after 60 min p.i. [18F]Fluoroacetate was readily accumulated in HT-29 tumors (tumor/muscle 1.75 ± 0.20 mean ± SEM, n=6) as shown in small animal PET studies (Fig. 2).

References: [1] L.-Q. Sun et al. Nucl. Med. Biol., 2006, 33, 153-158.

Conclusion:

The robust and reproducible remotely-controlled two step/one pot synthesis of [18F]fluoroacetate starting from readily available (methanesulfonyloxy)-acetic acid tert.-butyl ester 3a as a novel labelling precursor represents an alternative to the published procedures. A comparing discussion of data obtained with [11C]acetate in rats and mice will be presented.