Ohmomo Y, Yokoyama A, Yamauchi Y, Horiuchi K, Saji H, Tanaka C, Torizuka K
Int J Nucl Med Biol. 1985;12(1):47-52. doi: 10.1016/0047-0740(85)90012-9.
Highly purified high and low molecular weight urokinase (H-UK and L-UK) were labeled with 67Ga using deferoxamine (DF) as a bifunctional chelating agent. The labeling efficiency was 91.7% for the H-UK, and 90.4% for the L-UK, respectively. The 67Ga labeled UK (67Ga-DF-UK) fully retained the enzymatic activity of the parent UK. Studies on the in vivo behavior of the 67Ga labeled UK in rabbits showed a very rapid blood clearance with half-life of 4 min (67Ga-DF-L-UK) to 8 min (67Ga-DF-H-UK). Studies carried out in rabbits with induced thrombi in the femoral vein showed thrombus-to-blood 67Ga-DF-UK activity ratios, 2h after injection, of 2.00-3.08 for the H-UK, and 0.84-1.65 for the L-UK, respectively, with thrombi aged 4 to 3 days. A dose effect of the 67Ga-DF-H-UK on its thrombus accumulation was observed. Gel chromatographic analysis of plasma samples withdrawn from those animals injected with this radiopharmaceutical revealed a reduction of the 67Ga-DF-UK effectiveness due to complexation with protein inhibitors. This led to formation of high molecular weight complexes which was reflected in the very fast blood clearance. Its implication in thrombus accumulation is discussed. In conclusion, usefulness of DF for labeling UK with 67Ga or 68Ga with no alteration of UK enzymatic properties was demonstrated. The use of 67Ga-DF-UK as a diagnostic or therapeutic radiopharmaceutical is promising.
使用去铁胺（DF）作为双功能螯合剂，用67Ga标记高纯度的高分子量和低分子量尿激酶（H-UK和L-UK）。H-UK的标记效率分别为91.7%，L-UK的标记效率为90.4%。67Ga标记的尿激酶（67Ga-DF-UK）完全保留了母体尿激酶的酶活性。对67Ga标记的尿激酶在兔体内行为的研究表明，其血液清除非常迅速，半衰期为4分钟（67Ga-DF-L-UK）至8分钟（67Ga-DF-H-UK）。在兔股静脉诱导血栓的研究中，注射后2小时，对于4至3天龄的血栓，H-UK的血栓与血液67Ga-DF-UK活性比为2.00 - 3.08，L-UK为0.84 - 1.65。观察到67Ga-DF-H-UK对其血栓积累有剂量效应。对注射这种放射性药物的动物抽取的血浆样本进行凝胶色谱分析发现，由于与蛋白质抑制剂络合，67Ga-DF-UK的有效性降低。这导致形成高分子量复合物，这反映在非常快的血液清除中。讨论了其在血栓积累中的意义。总之，证明了DF用于用67Ga或68Ga标记尿激酶且不改变尿激酶酶学性质的有效性。67Ga-DF-UK作为诊断或治疗性放射性药物的应用前景广阔。
