Lohrmann Christian, Zhang Hanwen, Thorek Daniel L J, Desai Pooja, Zanzonico Pat B, O'Donoghue Joseph, Irwin Christopher P, Reiner Thomas, Grimm Jan, Weber Wolfgang A
Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
J Nucl Med. 2015 May;56(5):805-11. doi: 10.2967/jnumed.114.149054. Epub 2015 Apr 3.
(90)Y has been used to label various new therapeutic radiopharmaceuticals. However, measuring the radiation dose delivered by (90)Y is challenging because of the absence of suitable γ emissions and its low abundance of positron emissions. For the treatment of prostate cancer, radiolabeled gastrin-releasing peptide receptor (GRPr) antagonists have yielded promising results in mouse models. In this study, we evaluated whether Cerenkov luminescence imaging (CLI) could be used to determine radiation doses of a (90)Y-labeled GRPr antagonist in nude mice.
Mice bearing subcutaneous prostate cancer xenografts were injected with 0.74-18.5 MBq of the (90)Y-labeled GRPr antagonist DOTA-AR and underwent in vivo and ex vivo CLI at 1-48 h after injection. After imaging, animals were sacrificed, their tumors and organs were harvested, and the activity concentration was measured by liquid scintillation counting. In a second set of experiments, Cerenkov photon counts for tumor and kidney on in vivo CLI were converted to activity concentrations using conversion factors determined from the first set of experiments.
(90)Y-DOTA-AR concentration in the 3 tumor models ranged from 0.5% to 4.8% of the injected activity per gram at 1 h after injection and decreased to 0.05%-0.15 injected activity per gram by 48 h after injection. A positive correlation was found between tumor activity concentrations and in vivo CLI signal (r(2) = 0.94). A similar correlation was found for the renal activity concentration and in vivo Cerenkov luminescence (r(2) = 0.98). Other organs were not distinctly visualized on the in vivo images, but ex vivo CLI was also correlated with the radioactivity concentration (r(2) = 0.35-0.94). Using the time-activity curves from the second experiment, we calculated radiation doses to tumor and kidney of 0.33 ± 0.12 (range, 0.21-0.66) and 0.06 ± 0.01 (range, 0.05-0.08) Gy/MBq, respectively.
CLI is a promising, low-cost modality to measure individual radiation doses of (90)Y-labeled compounds noninvasively. The use of Cerenkov imaging is expected to facilitate the development and comparison of (90)Y-labeled compounds for targeted radiotherapy.
钇-90（90Y）已被用于标记各种新型治疗性放射性药物。然而，由于缺乏合适的γ射线发射且其正电子发射丰度较低，测量钇-90所释放的辐射剂量具有挑战性。对于前列腺癌的治疗，放射性标记的胃泌素释放肽受体（GRPr）拮抗剂在小鼠模型中已产生了有前景的结果。在本研究中，我们评估了切伦科夫发光成像（CLI）是否可用于确定裸鼠体内钇-90标记的GRPr拮抗剂的辐射剂量。
将皮下接种前列腺癌异种移植物的小鼠注射0.74 - 18.5 MBq的钇-90标记的GRPr拮抗剂DOTA - AR，并在注射后1 - 48小时进行体内和体外CLI。成像后，处死动物，收获其肿瘤和器官，并通过液体闪烁计数测量活度浓度。在第二组实验中，使用从第一组实验确定的转换因子，将体内CLI上肿瘤和肾脏的切伦科夫光子计数转换为活度浓度。
在3个肿瘤模型中，钇-90 - DOTA - AR在注射后1小时的浓度范围为每克注射活度的0.5%至4.8%，到注射后48小时降至每克注射活度的0.05% - 0.15%。发现肿瘤活度浓度与体内CLI信号之间呈正相关（r² = 0.94）。肾脏活度浓度与体内切伦科夫发光之间也发现了类似的相关性（r² = 0.98）。在体内图像上其他器官未清晰显示，但体外CLI也与放射性浓度相关（r² = 0.35 - 0.94）。使用第二个实验的时间 - 活度曲线，我们计算出肿瘤和肾脏的辐射剂量分别为0.33±0.12（范围，0.21 - 0.66）和0.06±0.01（范围，0.05 - 0.08）Gy/MBq。
CLI是一种有前景的、低成本的方式，可无创测量钇-90标记化合物的个体辐射剂量。切伦科夫成像的应用有望促进钇-90标记化合物用于靶向放射治疗的开发和比较。
