Hall Lance T, Titz Benjamin, Robins H Ian, Bednarz Bryan P, Perlman Scott B, Weichert Jamey P, Kuo John S
Department of Radiology, University of WisconsinMadison, WI, USA.
Department of Carbone Cancer Center, University of WisconsinMadison, WI, USA.
Am J Nucl Med Mol Imaging. 2017 Sep 1;7(4):157-166. eCollection 2017.
CLR1404 is a cancer-selective alkyl phosphocholine (APC) analog that can be radiolabeled with I for PET imaging, I for targeted radiotherapy and/or SPECT imaging, or I for targeted radiotherapy. Studies have demonstrated avid CLR1404 uptake and prolonged retention in a broad spectrum of preclinical tumor models. The purpose of this pilot trial was to demonstrate avidity of I-CLR1404 in human brain tumors and develop a framework to evaluate this uptake for use in larger studies. 12 patients (8 men and 4 women; mean age of 43.9 ± 15.1 y; range 23-66 y) with 13 tumors were enrolled. Eleven patients had suspected tumor recurrence and 1 patient had a new diagnosis of high grade tumor. Patients were injected with 185 MBq ± 10% of I-CLR1404 followed by PET/CT imaging at 6-, 24-, and 48-hour. I-CLR1404 PET uptake was assessed qualitatively and compared with MRI. After PET image segmentation SUV values and tumor to background ratios were calculated. There was no significant uptake of I-CLR1404 in normal brain. In tumors, uptake tended to increase to 48 hours. Positive uptake was detected in 9 of 13 lesions: 5/5 high grade tumors, 1/2 low grade tumors, 1/1 meningioma, and 2/4 patients with treatment related changes. I-CLR1404 uptake was not detected in 1/2 low grade tumors, 2/4 lesions from treatment related changes, and 1/1 indeterminate lesion. For 6 malignant tumors, the average tumor to background ratios (TBR) were 9.32 ± 4.33 (range 3.46 to 15.42) at 24 hours and 10.04 ± 3.15 (range 5.17 to 13.17) at 48 hours. For 2 lesions from treatment related change, the average TBR were 5.05 ± 0.4 (range 4.76 to 5.33) at 24 hours and 4.88 ± 1.19 (range 4.04 to 5.72) at 48 hours. PET uptake had areas of both concordance and discordance compared with MRI. I-CLR1404 PET demonstrated avid tumor uptake in a variety of brain tumors with high tumor-to-background ratios. There were regions of concordance and discordance compared with MRI, which has potential clinical relevance. Expansion of these studies is required to determine the clinical significance of the I-CLR1404 PET findings.
CLR1404是一种癌症选择性烷基磷胆碱（APC）类似物，可通过用碘-124进行正电子发射断层扫描（PET）成像、碘-131进行靶向放射治疗和/或单光子发射计算机断层扫描（SPECT）成像、或碘-131进行靶向放射治疗来进行放射性标记。研究表明，在广泛的临床前肿瘤模型中，CLR1404摄取迅速且滞留时间延长。这项试点试验的目的是证明碘-124标记的CLR1404在人脑肿瘤中的摄取情况，并建立一个框架来评估这种摄取情况，以便用于更大规模的研究。纳入了12例患者（8例男性和4例女性；平均年龄43.9±15.1岁；范围23 - 66岁），共13个肿瘤。11例患者怀疑肿瘤复发，1例患者新诊断为高级别肿瘤。患者注射185 MBq±10%的碘-124标记的CLR1404，随后在6小时、24小时和48小时进行PET/CT成像。对碘-124标记的CLR1404的PET摄取进行定性评估，并与磁共振成像（MRI）进行比较。在PET图像分割后，计算标准化摄取值（SUV）和肿瘤与背景比值。在正常脑组织中未发现碘-124标记的CLR1404有明显摄取。在肿瘤中，摄取倾向于在48小时时增加。在13个病灶中的9个检测到阳性摄取：5/5个高级别肿瘤、1/2个低级别肿瘤、1/1个脑膜瘤以及2/4例有治疗相关改变的患者。在1/2个低级别肿瘤、2/4个治疗相关改变的病灶以及1/1个不确定病灶中未检测到碘-124标记的CLR1404摄取。对于6个恶性肿瘤，24小时时平均肿瘤与背景比值（TBR）为9.32±4.33（范围为3.46至15.42），48小时时为10.04±3.15（范围为5.17至13.17）。对于2个治疗相关改变的病灶，24小时时平均TBR为5.05±0.4（范围为4.76至5.33），48小时时为4.88±1.19（范围为4.04至5.72）。与MRI相比，PET摄取既有一致区域也有不一致区域。碘-124标记的CLR1404的PET显示在多种脑肿瘤中有明显的肿瘤摄取，肿瘤与背景比值高。与MRI相比存在一致和不一致区域，这具有潜在的临床相关性。需要扩大这些研究以确定碘-124标记的CLR1404的PET结果的临床意义。
