Positron tomographic quantitation of neuroreceptors in human brain in vivo--with special reference to the D2 dopamine receptors in caudate nucleus.

The radioligand 3-N-[11C]methylspiperone (11C-NMSP) binds to D2 dopamine receptors with high affinity. We determined the rate of binding in 12 male volunteers, using a 3-compartment model to relate the time integral of the tracer plasma concentration to the distribution of the tracer in the caudate nucleus measured by positron tomography. The rate of binding (k3) was defined as the product of the bimolecular association rate (kon) and the quantity of available receptors (B'max). We calculated the product as the ratio between the steady-state rate of accumulation and the volume of distribution in the caudate nucleus. The average value was 0.100 min-1 in the normal volunteers. We varied k3 by reducing the number of available receptors with the D2 dopamine receptor blocking agent haloperidol ingested 4 hours before the tracer injection. In the normal volunteers, we calculated a receptor density of 17 pmol g-1 in the caudate nucleus and an inhibitory constant of haloperidol of 3 nM by comparing tracer accumulation in the absence and presence of the blocking agent. Bmax was also calculated in older men, drug-naive schizophrenics, and drug-treated schizophrenics (all men). The lowest value of Bmax was calculated in the older men (6 pmol g-1); the highest in the two groups of schizophrenic patients (39 and 41 pmol g-1, respectively).