Lam A S, Puncher M R, Blower P J
Research School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Eur J Nucl Med. 1996 Dec;23(12):1575-82. doi: 10.1007/BF01249619.
The purpose of this investigation was to characterise the in vivo chemistry and binding mechanisms of technetium-99m dimercaptosuccinic acid [99mTc(V)DMSA]. Biodistribution was studied in mice by frozen section whole-body autoradiography and microautoradiography in selected tissues. Binding to bone mineral analogues was studied in vitro using various forms of calcium phosphate and hydroxyapatite under varied conditions. Similar studies with 99mTc-hydroxymethylene diphosphonate (HDP) were also carried out for comparison. The in vivo stability of 99mTc(V)DMSA was monitored by high-performance liquid chromatographic analysis of blood and urine samples taken over 24 h from patients injected with the tracer. Whole-body autoradiography shows that 99mTc(V)DMSA has highest affinity for bone (cortical rather than medullary) in mice. Substantial uptake of the tracer was also observed in the kidney (cytoplasm of cortical renal tubular cells). No specific localisation was observed in the liver at either the microscopic or the macroscopic level. While 99mTc-HDP bound strongly to calcium phosphates under all conditions, 99mTc(V)DMSA binding was inhibited in the presence of phosphate and was stronger at pH 6.0 than at pH 7. 4. In non-phosphate buffers, however, the binding of 99mTc(V)DMSA remained high across the pH range 4-7.4. 99mTc(V)DMSA binds to calcium phosphates chemically unaltered, and no radioactive species other than the three isomers of 99mTc(V)DMSA were detected in blood or urine samples taken from patients up to 24 h after injection. 99mTc(V)DMSA is stable in vivo, and no conversion of the complex to other chemical species needs to be invoked to explain its uptake in bone metastases or soft tissue tumour. Bone affinity may be due to reversible binding of the unaltered complex to the mineral phase of bone.
本研究的目的是表征锝-99m二巯基丁二酸[99mTc(V)DMSA]的体内化学性质和结合机制。通过冷冻切片全身放射自显影术在小鼠体内研究其生物分布，并在选定组织中进行显微放射自显影。在体外，使用各种形式的磷酸钙和羟基磷灰石在不同条件下研究其与骨矿物质类似物的结合。还进行了99mTc-羟亚甲基二膦酸盐（HDP）的类似研究以作比较。通过对注射示踪剂的患者在24小时内采集的血液和尿液样本进行高效液相色谱分析，监测99mTc(V)DMSA的体内稳定性。全身放射自显影显示，99mTc(V)DMSA对小鼠骨骼（皮质而非髓质）具有最高亲和力。在肾脏（皮质肾小管细胞的细胞质）中也观察到示踪剂的大量摄取。在显微镜或宏观水平上，肝脏均未观察到特异性定位。虽然99mTc-HDP在所有条件下都与磷酸钙强烈结合，但99mTc(V)DMSA的结合在有磷酸盐存在时受到抑制，并且在pH 6.0时比在pH 7.4时更强。然而，在非磷酸盐缓冲液中，99mTc(V)DMSA在pH 4 - 7.4范围内的结合仍然很高。99mTc(V)DMSA以化学未改变的形式与磷酸钙结合，在注射后长达24小时从患者采集的血液或尿液样本中未检测到除99mTc(V)DMSA的三种异构体以外的放射性物质。99mTc(V)DMSA在体内稳定，无需调用复合物向其他化学物种的转化来解释其在骨转移瘤或软组织肿瘤中的摄取。骨亲和力可能是由于未改变的复合物与骨矿物质相的可逆结合。
