Jonkhoff A R, Plaizier M A, Ossenkoppele G J, Teule G J, Huijgens P C
Free University Hospital, Department of Haematology, Amsterdam, The Netherlands.
Br J Cancer. 1995 Dec;72(6):1541-6. doi: 10.1038/bjc.1995.544.
Gallium-67 (67Ga) accumulates in malignant tissues via the transferrin receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, pharmacokinetics, toxicity and preliminary efficiency of high-dose 67Ga injected intravenously (i.v.) in patients with acute leukaemia not responding to conventional therapy. Twelve doses of 36-105 mCi of Gallium67 citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acute myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)acute toxicity was observed. Independent of the administered dose, whole-blood radioactivity levels 10 min after administration measured only 1.25 +/- 1.39 microCi ml-1, indicating a large volume of distribution. Urine excretion in the first 24 h ranged from 18% to 51.5% (median 29.5%) of the administered dose. Cellular uptake of 67Ga was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 +/- 0.03 cGy mCi-1. Red marrow dose was estimated to be between 0.18 +/- 0.02 and 0.97 +/- 0.12 cGy mCi-1. One definite response was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three other patients showed transient reductions in white blood cell counts without disappearance of blasts from the peripheral blood. We conclude that high-dose i.v. 67Ga can be safely administered but that the uptake of 67Ga in blast cells must increase to make 67Ga therapeutically useful in patients with relapsed leukaemia.
镓 - 67（67Ga）通过转铁蛋白受体在恶性组织中蓄积，无需单克隆抗体，并发射具有细胞毒性的低能电子。在本研究中，我们调查了静脉注射（i.v.）高剂量67Ga对常规治疗无反应的急性白血病患者的可行性、药代动力学、毒性和初步疗效。在一项初步研究中，以推注方式向8例耐药白血病患者给予了12剂36 - 105毫居里的柠檬酸镓67。所有5例急性髓系白血病（AML）患者和3例急性淋巴细胞白血病（ALL）患者均患有耐药疾病或耐药复发。未观察到（亚）急性毒性。无论给药剂量如何，给药后10分钟全血放射性水平仅为1.25±1.39微居里/毫升，表明分布容积较大。前24小时尿液排泄量占给药剂量的18%至51.5%（中位数29.5%）。67Ga的细胞摄取低于先前的体外研究。全身辐射剂量估计为0.25±0.03厘戈瑞/毫居里。红骨髓剂量估计在0.18±0.02至0.97±0.12厘戈瑞/毫居里之间。在1例ALL患者中观察到1例明确反应，皮肤病变消失，肿大脾脏恢复正常，白细胞减少明显。其他3例患者白细胞计数短暂下降，但外周血原始细胞未消失。我们得出结论，高剂量静脉注射67Ga可以安全给药，但67Ga在原始细胞中的摄取必须增加，才能使67Ga对复发白血病患者具有治疗作用。
