Evaluation of technetium 99m cyclobutylpropylene amine oxime as a potential brain perfusion imaging agent for SPET

Abstract

Technetium 99md,l-cyclobutylpropylene amine oxime (^99mTc-CBPAO) has been developed as a brain-imaging agent for single photon emission tomography (SPET).^99mTc-CBPAO can be prepared using a simple labelling procedure suitable for routine clinical use. It has a high in vitro stability, as has been demonstrated by high-pressure liquid chromatography (HPLC) analysis. This shows that 3 h after labelling, less than 5% of the primary lipophilic complex which is capable of crossing the blood-brain barrier (BBB) converts to a secondary hydrophilic complex. Brain uptake (% dose/g wet tissue) of^99mTc-CBPAO, determined at 5 and 30 min after injection in two groups of six adult male Sprague-Dawley rats, was found to be 0.74±0.06 and 0.73±0.13 (mean ± SD), respectively. These values are not significantly different from those obtained repeating the experiment with^99mTc-labelled hexamethylpropylene amine oxime (^99mTc-HMPAO) (0.72±0.15 at 5 min and 0.88 ± 0.24 at 30 min after injection). Since the rat brain uptake of^99mTc-CBPAO remained unchanged for a period of time suitable for tomographic study, the comparison of the two tracers was extended to two groups of ten patients. The latter were affected by neurological and psychiatric disorders and were studied with SPET. Human brain uptake (% dose/cc cortical grey matter) of^99mTc-CBPAO and^99mTc-HMPAO were 3.04±0.57 and 4.22±0.46 (mean × 10⁻³ ± SD × 10⁻³), respectively, with a 32% significant difference. In two other groups of five patients, the first transit time-activity curves of the two tracers were compared. From the analysis of these curves we suggest that^99mTc-CBPAO has a higher binding effect on blood components and/or a higher degradation rate in blood than that of^99mTc-HMPAO. This may account for the reduced human brain uptake. In conclusion, SPET images of^99mTc-CBPAO reflect blood perfusion, and they have a good diagnostic quality. The main advantage of^99mTc-CBPAO is its in vitro stability; however,^99mTc-HMPAO is a superior imaging agent.