Synthesis of d- and l-Form of 99mTc-HMPAO, and Comparison of Brain Uptake / 대한핵의학회잡지

PURPOSE: 99mTc-HMPAO is a radiopharmaceutical for imaging cerebral blood flow. HMPAO (RR, SS)-4,8- diaza-3,6,6,9-tetramethylundecan-2,10- dione bisoxime) has three stereoismers such as, meso-, d-, and l-HMPAO. Techentium complexes of meso-HMPAO and d,l-HMPAO are known to have different in vivo brain uptakes. In this study, enantiomers of HMPAO (d-HMPAO and l-HMPAO) were separated from d,l-HMPAO. These enantiomers were labeled with 99mTc and the biodistribution studies were performed in mice. MATERIALS AND METHODS: An intermediate imine product was produced from 2,3-butanedione monooxime and 2,2-dimethyl- 1,3-propanediamine (54% yield) and was reduced into a mixture of three isomers (35% yield). The meso-isomer was separated from d,l-mixture by repeated fractional crystallization (11% yield). The d- and l-enantiomers were subsequently separated by co-crystallization with optical isomers of tartaric acid (25% and 5% yield, respectively). Each enantiomeric HMPAO was labeled with 99mTc by reacting with SnCl2 2H2O and 99mTc-pertechnetate. Biodistribution study was performed 1 hr after tail vein injection to ICR mice. RESULTS: Radiochemical purities of each compound were over 80%. In biodistribution study, the brain uptakes of d,l- d- and l-form were 1.34, 1.12 and 1.67% ID/g, respectively. In case of l-Isomer the brain uptake was higher (1.5 fold) than d-isomer. CONCLUSION: We successfully purified each enantiomeric HMPAO. In biodistribution study of stereoismers of 99mTc-HMPAO in mice, l-HMPAO may show better brain image than d,l-HMPAO which was supplied in a commercial kit.

Differential Skeletal Response to Ovariectomy in Young and Old Rats

OBJECTIVE: The purpose of this study is to evaluate the loss of bone mineral density on ovariectomized (ovx) rat in young and old rats. METHOD: Total 110 Sprague-Dawley female rats which composed of 3 months aged 88 rats and 12 months aged 22 rats were used. They were divided randomly into 5 ovx groups (15 rats for each group) and 5 sham operation group (7 rats for each group). The bone mineral density was measured by Hologic 4,500 Fan Beam bone densitometry at the time of second postoperation week, 4th week, 8th week, and 16th week in young aged group and 4th, 8th week in old aged group. RESULTS: The bone mineral density in young ovx rats was decreased measured at 2 week, 4 week and 8 week, but not 16 week compared with that of sham operation rats (p0.05). CONCLUSION: For the purpose of osteoporosis inducing experiment, young aged rat is more reliable for the detection of bone density change than old aged rat and the bone mineral density change will be continued at least 16 week postovariectomy period.