SYNTHESIS AND PRELIMINARY EVALUATION OF [C-11] KF15372, A SELECTIVE ADENOSINE A(1) ANTAGONIST

As a radioligand for mapping the presynaptic adenosine A, receptors in the central nervous system by PET, [1-propyl-C-11]8-dicyclopropylmethyl-1,3-dipropylxanthine ([C-11]KF15372), a selective adenosine A(1) antagonist, was prepared by the reaction of 8-dicyclopropylmethyl-3-propylxanthine and [C-11]propyl iodide with decay-corrected radiochemical yield of 5% based. on the [C-11]propyl iodide, radiochemical purity of >99%, sp. act. of 10-56 GBq/mu mol and preparation time of 45-55 min. Another C-11-labeled A, antagonist with much lower affinity for the A, receptors, 7-[C-11]methyl-KF15372 ([C-11]KF17109), was also prepared using [C-11]methyl iodide with a decay-corrected radiochemical yield of >50%. In mice, the brain uptake of [C-11]KF15372 (1.91%ID/g at 5 min) decreased gradually with time. Carrier KF15372 competitively reduced the brain uptake to a level (43% of the control) comparable to the brain uptake of [C-11]KF17109. On the other hand, an A, antagonist 3,7-dimethyl-1-propargylxanthine showed no effect on the brain uptake of [C-11]KF15372. The results show that [C-11]KF15372 has potential as a PET radioligand for mapping the adenosine A(1) receptors and that [C-11]KF17109 may be a reference compound reflecting the non-specific uptake of the [C-11]KF15372.