John C S, Kung M P, Billings J, Kung H F
Department of Radiology, University of Pennsylvania, Philadelphia 19104.
Int J Rad Appl Instrum B. 1991;18(5):551-6. doi: 10.1016/0883-2897(91)90117-4.
In developing new ligands as potential brain and heart perfusion imaging agents two ligands based upon N2S2 donor atoms with the biphenyl backbone were synthesized. Biphenyl-2,2'-bis(N-1-amino-2-methyl-propane-2-thiol) (BP-BAT-TM) and biphenyl-2,2'-bis(N-1-amino-2-ethyl-butane-2-thiol) (BP-BAT-TE) form stable, neutral and lipid soluble complexes with [99mTc]pertechnetate in the presence of tin(II) tartarate as a reducing agent. The [99mTc]BP-BAT-TM complex penetrates the blood-brain barrier following i.v. injection into rats. Washout from the brain is fast, indicating no retention. The biodistribution of [99mTc]BP-BAT-TE in rats showed an initial heart uptake (0.8%/organ, at 2 min) and a slow washout (0.74% at 15 min). No brain uptake was found (0.05%). Significant uptake and retention in liver was observed. An imaging study of [99mTc]BP-BAT-TE in a monkey showed no brain uptake and a clear indication of liver uptake and gall bladder clearance. These results indicate that this ligand system may be suitable as the basic core structure for the development of new imaging agents. Further studies with structural variations in the biphenyl backbone are warranted to develop new 99mTc imaging agents for clinical applications.
在开发作为潜在脑和心脏灌注显像剂的新配体时，合成了两种基于具有联苯主链的N2S2供体原子的配体。联苯-2,2'-双(N-1-氨基-2-甲基丙烷-2-硫醇)(BP-BAT-TM)和联苯-2,2'-双(N-1-氨基-2-乙基丁烷-2-硫醇)(BP-BAT-TE)在酒石酸锡(II)作为还原剂的存在下与高锝酸盐[99mTc]形成稳定、中性且脂溶性的配合物。静脉注射到大鼠体内后，[99mTc]BP-BAT-TM配合物可穿透血脑屏障。从脑中清除很快，表明没有滞留。[99mTc]BP-BAT-TE在大鼠体内的生物分布显示最初心脏摄取(2分钟时为0.8%/器官)且清除缓慢(15分钟时为0.74%)。未发现脑摄取(0.05%)。观察到肝脏有显著摄取和滞留。对猴子进行的[99mTc]BP-BAT-TE成像研究显示没有脑摄取，且明确显示有肝脏摄取和胆囊清除。这些结果表明该配体系统可能适合作为开发新型显像剂的基本核心结构。有必要对联苯主链进行结构变化的进一步研究，以开发用于临床应用的新型99mTc显像剂。
