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Regional distribution of brain perfusion imaging agents, [131I]N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-iodobenzyl]1,3 propanediamine (HIPDM) and [131I]-N-isopropyl-p-iodoamphetamine (IMP), was compared with the distribution of patterns of [14C]L-methionine and [14C]D-glucose in normal and tumour bearing rat brains using autoradiographic technique. There was higher concentration of the radiopharmaceutical in grey than white matter in normal rat brain. Autoradiographs of brain tumour sections showed very low uptake of [131I]HIPDM and [131I]IMP as compared to normal brain tissue. There was moderate concentration of [14C]D-glucose and avid uptake of [14C]L-methionine in tumours. Autoradiographic study is useful for evaluating distribution patterns of radiopharmaceuticals.

Biodistribution of N-isopropyl-p-iodoamphetamine (IMP) was evaluated in mice. After synthesis of IMP and exchange labeling with radioactive iodine, IMP was injected intravenously in male ddY mice. Activity in the brain reached 8.0 (%dose/g), at 10 min after injection and it was almost constant till 120 min. Activities in the lung and heart were high just after injection, decreased rapidly and was almost constant from 30 to 120 min. Activity in the liver increased slowly compared with other organs, and reached peak level at 60 min. In autoradiography, almost the same activity in the spinal cord as the brain was observed. Uptake and excretion of IMP were shown in kidneys and stomach, which may be the main route of the excretion of IMP and their metabolites. We concluded IMP showed good uptake in the central nervous system.

Factor analysis of dynamic scintigraphic studies has been proposed for a variety of clinical applications. This method also called FADS (Factor Analysis of Dynamic Structures) enables spatial separation of complex images into discrete factors according to their time/activity characteristics. FADS, which does not require a priori formulation of a compartmental model of tracer kinetics, is particularly suitable for the evaluation of new radiolabeled compounds as potential radiopharmaceuticals. In animals as well as in humans it is possible to obtain information on the spatial time-distribution of tracers by analyzing computer acquired scintigraphic studies. On the basis of data obtained and analyzed with this method using [123I]IMP in humans, dogs, rabbits and rats, with two 99mTc labeled monoclonal antibodies in dogs and with 99mTc DTPA in renal transplants, we recommend this method as an adjunct in radiopharmaceutical development and evaluation.

Demethylation of psychotomimetic compounds was measured by labeling each methyl and methoxy substitutent separately with 14C and injecting it into rats, intravenously and intracerebrally. Expired [14C]CO2 was measured continuously and the resultant multi-exponential curves yielded rates and integral demethylation. 5-Methoxy-N,N-dimethyltryptamine was not demethylated, eliminating one proposed metabolic pathway. 2,4,5-Trimethoxyphenalkylamines were demethylated less in the brain than peripherally, markedly so at the p-methoxy position, suggesting a possible biochemical site for endogenous induction of psychosis.

The relation between brain uptake of radiolabeled n-isopropyl-p-iodoamphetamine [( 123I]IMP) and serotonin re-uptake sites was studied in vivo by lesioning serotonergic nerve endings. The reduction of brain serotonin demonstrated the effectiveness of the procedure. Accumulation of radioactivity/g brain tissue was higher in the lesioned than in the sham-operated rats. This was explained by the loss of body weight of the lesioned animals, allowing an increased distribution to the brain. These results demonstrate that the in vivo distribution and binding of [123I]IMP in the brain is not limited to the specific serotonin re-uptake sites on nerve endings.