Measurement of plasma metabolites of (S)-5-[¹²³I]iodo-3-(2-azetidinylmethoxy)pyridine (5-IA-85380), a nicotinic acetylcholine receptor imaging agent, in nonhuman primates

The iodinated analog (S)-5-[¹²³I]iodo-3-(2-azetidinylmethoxy)pyridine of A-85380 is a new potential SPECT tracer specific for the α4β2 subtype nicotinic acetylcholine receptors, which play an important role in neurodegenerative diseases and in tobacco dependence. To evaluate the possibility of using this tracer for the in vivo quantification of these receptors, an accurate measurement of the plasma concentration of the parent compound is necessary. In human or nonhuman primate whole blood as well as in plasma, the parent compound is only stable for approximately 5 min, after which it decomposes. The radioligand is stable in the injection solution and in protein-free (>30 K M.W.) plasma ultrafiltrate for at least 18 h. To preserve the parent compound in plasma the radioactive plasma must be mixed with equal volumes of acetonitrile within 5 min after its collection or, alternatively, radioactive blood should be collected and mixed with sodium azide (3 mg/ml blood). The in vivo metabolism of [¹²³I]5-IA resulted in two components: a radiometabolite that is less lipophilic than the parent compound and a polar radiometabolite that is not free radioiodide because of the absence of radioactivity accumulation in the thyroid.