In vivo evaluation in mice and metabolism in blood of human volunteers of [I-123]iodo-PK11195: a possible single-photon emission tomography tracer for visualization of inflammation

We report the in vivo evaluation (biodistribution, displacement and metabol ization in blood, brain and heart) in mice and the metabolism in blood of h uman volunteers of iodine-123 labelled 1-(2-iodophenyl)-N-methyl-N-(1-methy l-propyl)-3-isoquinoline carboxamide ([I-123]iodo-PK11195), a potential rad ioligand for visualization of inflammation in humans by single-photon emiss ion tomography. In three series of 18 white mice (NMRI, 20-25 g), the conce ntration of radioactivity was measured during 48 h, Blood samples were take n, organs and intestines were excised, excretion was collected and all tiss ues were weighed and counted for radioactivity. The tissue uptake of radioa ctivity was measured as % of the injected activity/g of tissue. The excreti on was expressed as % of the injected activity. Selective tissue uptake was investigated by pretreatment of another three series of 18 mice with cold PK11195 (1 mg/kg body weight). There was an inflow of [I-123]iodo-PK11195 i n the brain and among peripheral organs, heart (42.3%), lungs (133.5%) and kidneys (18.4%) had the highest uptake. After pretreatment with cold PK1119 5, there was a decrease in accumulation in the latter three organs, especia lly in heart (ca. 55%) and lungs (ca. 80%). Metabolite analysis was perform ed using high-performance liquid chromatography (HPLC). First, the extracti on yield of [I-123]iodo-PK11195 from blood and tissue was assessed, and fou nd to be >90%. From blank blood samples and organs spiked with [I-123]iodo- PK11195 it was concluded that no metabolization took place during the extra ction procedure. Analysis of plasma, brain and heart of mice showed that 10 min p.i. [I-123]iodo-PK11195 was the only significant (ca. 95%) radioactiv e compound in brain and heart where-as in plasma other radioactive products (>60%) appeared. Analysis of plasma samples of the three human volunteers at 7, 20, 37 and 50 min p.i. showed that [I-123]iodo-PK11195 rapidly decomp oses into two polar metabolites, which at these time points accounted for, respectively 31%, 62%, 75% and 77% of the total activity.