Bombesin receptors in rat brain: High resolution scan with 99mTc BN1.1

Bombesin (BN) like peptides modulate some functions of central nervous system (CNS) such as feeding and sleep awake cycle. Other roles, including modulation of psychiatric disorders, have been hypothesised by some researchers. A CNS map of bombesin receptors ( BNR) would help understanding the complex cerebral functions of BN like peptides, but this is not available. 99mTc labelled BN-like peptide scan of CNS is the ideal method to obtain the above map. Our group previously reported synthesis, 99mTc labelling and usefulness for cancer diagnosis of BN-like peptides. We have also developed High Resolution (HR) gamma cameras: HR imaging is mandatory to study CNS of small animals. Methods: We performed HR Planar and SPECT images of rat brain with A) pertechnetate and 99mTc HMPAO to make comparison with labelled BN and B) a 99mTc BN- like peptide. Study A was performed on 3 , study B on 5 rats. Images were acquired under mild anaesthesia with a 2mm space resolution, high sensitivity, 25 cm2 FOV Imaging Probe ( Patented, 4 Patents US and EU). Study B was performed with the BN-like peptide 99mTc BN1.1 ( Patented), 37 MBq in the tail vein. HR Images were acquired at 10, 30 and 60 min after injection. Autopsy was performed at 60 min. Brains were removed, chilled, dissected and the per cent of brain dose was calculated for each brain region. Results: Labelling yield of 99mTc BN1.1 was 97± 0.3%. HR images of 99mTc BN1.1 were significantly different from those of pertechnetate and 99mTc HMPAO. 99mTc BN1.1 showed clear, well defined images of fronto-lateral, temporal cortex, cerebellum and brain stems. Hypothalamus, basal ganglia and amygdala were also detected, though with some difficulties. 10, 30 and 60 min images of 99mTc BN1.1 were very similar, confirming the already-reported-by-us very fast uptake of 99mTc BN. Biodistribution after autopsy showed that only 0.035 of the injected dose is taken up by CNS. Of the dose detected in brain, amygdala and hypothalamus took up 10% each, cerebellum 14%, hippocampus 7.5 %, basal ganglia 6.5% and frontal cortex 4.0 %. Comments: We obtained a map of BNR distribution in rat brain. HR camera images of BNR distribution inside rat brain were consistent with biodistribution after autopsy. Though this distribution is much more complex than prevision, it is consistent with known circuits for regulation of feeding and sleep. Cortical uptake is an intriguing finding that deserves further studies.