Sp. Hume et al., PHARMACOLOGICAL CONSTRAINTS ASSOCIATED WITH POSITRON EMISSION TOMOGRAPHIC SCANNING OF SMALL LABORATORY-ANIMALS, European journal of nuclear medicine, 25(2), 1998, pp. 173-176
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.