Postema Ernst J, Börjesson Pontus K E, Buijs Wilhelmina C A M, Roos Jan C, Marres Henri A M, Boerman Otto C, de Bree Remco, Lang Margreet, Munzert Gerd, van Dongen Guus A M S, Oyen Wim J G
Department of Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands.
J Nucl Med. 2003 Oct;44(10):1690-9.
From December 1999 until July 2001, a phase I dose escalation study was performed with (186)Re-labeled bivatuzumab, a humanized monoclonal antibody against CD44v6, on patients with inoperable recurrent or metastatic head and neck cancer. The aim of the trial was to assess the safety and tolerability of intravenously administered (186)Re-bivatuzumab and to determine the maximum tolerated dose (MTD) of (186)Re-bivatuzumab. The data were also used for dosimetric analysis of the treated patients. Dosimetry is used to estimate the absorbed doses by nontarget organs, as well as by tumors. It can also help to explain toxicity that is observed and to predict organs at risk because of the therapy given.
Whole-body scintigraphy was used to draw regions around sites or organs of interest. Residence times in these organs and sites were calculated and entered into the MIRDOSE3 program, to obtain absorbed doses in all target organs except for red marrow. The red marrow dose was calculated using a blood-derived method. Twenty-one studies on 18 patients, 5 female and 16 male, were used for dosimetry.
The mean red marrow doses were 0.49 +/- 0.03 mGy/MBq for men and 0.64 +/- 0.03 mGy/MBq for women. The normal organ with the highest absorbed dose appeared to be the kidney (mean dose, 1.61 +/- 0.75 mGy/MBq in men and 2.15 +/- 0.95 mGy/MBq in women; maximum kidney dose in all patients, 11 Gy), but the doses absorbed are not expected to lead to renal toxicity. Other organs with doses exceeding 0.5 mGy/MBq were the lungs, the spleen, the heart, the liver, the bones, and the testes. The doses delivered to the tumor, recalculated to the MTD level of 1.85 GBq/m(2), ranged from 3.8 to 76.4 Gy, with a median of 12.4 Gy. A good correlation was found between platelet and white blood cell counts and the administered amount of activity per kilogram of body weight (r = -0.79).
Dosimetric analysis of the data revealed that the range of doses to normal organs seems to be well within acceptable and safe limits. Tumor doses ranged from 4 to 76 Gy. Given the acceptable tumor doses, (186)Re-labeled bivatuzumab could be a good candidate for future adjuvant radioimmunotherapy in patients with minimal residual disease.
1999年12月至2001年7月，对无法手术的复发性或转移性头颈癌患者进行了一项I期剂量递增研究，使用（186）Re标记的比伐单抗，一种抗CD44v6的人源化单克隆抗体。该试验的目的是评估静脉注射（186）Re-比伐单抗的安全性和耐受性，并确定（186）Re-比伐单抗的最大耐受剂量（MTD）。这些数据也用于对接受治疗患者的剂量学分析。剂量学用于估计非靶器官以及肿瘤所吸收的剂量。它还有助于解释观察到的毒性，并预测因所给予的治疗而处于危险中的器官。
使用全身闪烁显像来划定感兴趣部位或器官周围的区域。计算这些器官和部位的驻留时间，并输入MIRDOSE3程序，以获得除红骨髓外所有靶器官的吸收剂量。红骨髓剂量采用血液衍生方法计算。对18例患者（5例女性和16例男性）进行的21项研究用于剂量学分析。
男性红骨髓平均剂量为0.49±0.03 mGy/MBq，女性为0.64±0.03 mGy/MBq。吸收剂量最高的正常器官似乎是肾脏（男性平均剂量为1.61±0.75 mGy/MBq，女性为2.15±0.95 mGy/MBq；所有患者肾脏最大剂量为11 Gy），但预计所吸收的剂量不会导致肾毒性。剂量超过0.5 mGy/MBq的其他器官有肺、脾、心脏、肝脏、骨骼和睾丸。重新计算至1.85 GBq/m²的MTD水平时，肿瘤所接受的剂量范围为3.8至76.4 Gy，中位数为12.4 Gy。发现血小板和白细胞计数与每千克体重所给予的活度之间存在良好的相关性（r = -0.79）。
对数据的剂量学分析表明，正常器官的剂量范围似乎完全在可接受的安全限度内。肿瘤剂量范围为4至76 Gy。鉴于肿瘤剂量可接受，（186）Re标记的比伐单抗可能是未来对微小残留病患者进行辅助放射免疫治疗的良好候选药物。
