PHARMACOLOGICAL CONSTRAINTS ASSOCIATED WITH POSITRON EMISSION TOMOGRAPHIC SCANNING OF SMALL LABORATORY-ANIMALS

With the stated aim of scanning small regions of interest in mice, sev eral high-resolution positron emission tomographic (PET) systems are p resently under development. Some, however, have low sensitivity and re quire high doses of radioactivity to achieve count statistics adequate to reconstruct small volumes. Using in vivo dissociation constants fo r three carbon-11 labelled ligands previously measured in rat brain, t he present paper utilises simple saturation kinetics to estimate the l imits on radioactivity and specific activity, to minimise the degree o f receptor occupancy and achieve maximal specific binding of the radio ligand. The extent of the problem is exemplified by considering a high -affinity ligand (dissociation constant in vitro similar to 0.1 nM; in vivo similar to 5 nmol/kg i.v. injected dose), where routinely produc ed levels of specific activity (similar to 100 MBq/nmol) would limit t he activity injected into mice to similar to 0.1 MBq for a 1% receptor occupancy. If, as is feasible, the new generation of high resolution PET systems requires an injected activity >10 MBq, then a >100-fold in crease in specific activity would be needed for tracer kinetics to hol d. The paper highlights the need to consider realistically achievable goals if high-resolution PET is to be accepted as a viable methodology to acquire pharmacologically and physiologically accurate ligand-rece ptor binding data in mice.