Shen Sui, Forero Andres, LoBuglio Albert F, Breitz Hazel, Khazaeli M B, Fisher Darrell R, Wang Wenquan, Meredith Ruby F
Department of Radiation Oncology, Comprehensive Cancer Center, University of Alabama at Birmingham, Wallace Tumor Institute, Birmingham, Alabama 35294, USA.
J Nucl Med. 2005 Apr;46(4):642-51.
Pretargeted radioimmunotherapy (RIT) using CC49 fusion protein, comprised of CC49-(scFv)4 and streptavidin, in conjunction with 90Y/111In-DOTA-biotin (DOTA = dodecanetetraacetic acid) provides a new opportunity to improve efficacy by increasing the tumor-to-normal tissue dose ratio. To our knowledge, the patient-specific dosimetry of pretargeted 90Y/111In-DOTA-biotin after CC49 fusion protein in patients has not been reported previously.
Nine patients received 3-step pretargeted RIT: (a) 160 mg/m2 of CC49 fusion protein, (b) synthetic clearing agent (sCA) at 48 or 72 h later, and (c) 90Y/111In-DOTA-biotin 24 h after the sCA administration. Sequential whole-body 111In images were acquired immediately and at 2-144 h after injection of 90Y/111In-DOTA-biotin. Geometric-mean quantification with background and attenuation correction was used for liver and lung dosimetry. Effective point source quantification was used for spleen, kidneys, and tumors. Organ and tumor 90Y doses were calculated based on 111In imaging data and the MIRD formalism using patient-specific organ masses determined from CT images. Patient-specific marrow doses were determined based on radioactivity concentration in the blood.
The 90Y/111In-DOTA-biotin had a rapid plasma clearance, which was biphasic with <10% residual at 8 h. Organ masses ranged from 1,263 to 3,855 g for liver, 95 to 1,009 g for spleen, and 309 to 578 g for kidneys. The patient-specific mean 90Y dose (cGy/37 MBq, or rad/mCi) was 0.53 (0.32-0.78) to whole body, 3.75 (0.63-6.89) to liver, 2.32 (0.58-4.46) to spleen, 7.02 (3.36-11.2) to kidneys, 0.30 (0.09-0.44) to lungs, 0.22 (0.12-0.34) to marrow, and 28.9 (4.18-121.6) to tumors.
Radiation dose to normal organs from circulating radionuclide is substantially reduced using pretargeted RIT. Tumor-to-normal organ dose ratios were increased about 8- to 11-fold compared with reported patient-specific mean dose to liver, spleen, marrow, and tumors from 90Y-CC49.
使用由CC49-(scFv)4和链霉亲和素组成的CC49融合蛋白与90Y/111In-DOTA-生物素（DOTA = 十二烷四乙酸）进行预靶向放射免疫疗法（RIT），通过提高肿瘤与正常组织的剂量比为提高疗效提供了新机会。据我们所知，此前尚未报道过CC49融合蛋白后患者体内预靶向90Y/111In-DOTA-生物素的患者特异性剂量测定。
9名患者接受了三步预靶向RIT：(a) 160 mg/m2的CC49融合蛋白，(b) 48或72小时后给予合成清除剂（sCA），(c) sCA给药后24小时给予90Y/111In-DOTA-生物素。在注射90Y/111In-DOTA-生物素后立即以及2至144小时采集全身111In图像。采用背景和衰减校正的几何平均定量法进行肝脏和肺部剂量测定。采用有效点源定量法对脾脏、肾脏和肿瘤进行测定。根据111In成像数据和MIRD公式，使用从CT图像确定的患者特异性器官质量计算器官和肿瘤的90Y剂量。根据血液中的放射性浓度确定患者特异性骨髓剂量。
90Y/111In-DOTA-生物素具有快速的血浆清除率，呈双相性，8小时时残留量<10%。肝脏器官质量范围为1263至3855克，脾脏为95至1009克，肾脏为309至578克。患者特异性平均90Y剂量（cGy/37 MBq，或rad/mCi）全身为0.53（0.32 - 0.78），肝脏为3.75（0.63 - 6.89），脾脏为2.32（0.58 - 4.46），肾脏为7.02（3.36 - 11.2），肺部为0.30（0.09 - 0.44），骨髓为0.22（0.12 - 0.34），肿瘤为28.9（4.18 - 121.6）。
使用预靶向RIT可大幅降低循环放射性核素对正常器官的辐射剂量。与报道的90Y-CC49对肝脏、脾脏、骨髓和肿瘤的患者特异性平均剂量相比，肿瘤与正常器官的剂量比提高了约8至11倍。
