Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
J Nucl Med. 2014 Jun;55(6):995-1001. doi: 10.2967/jnumed.114.138180. Epub 2014 Apr 3.
Both radionuclide imaging and near-infrared fluorescent (NIRF) imaging have a high sensitivity to detect tumors in vivo. The combination of these modalities using dual-labeled antibodies may allow both preoperative and intraoperative tumor localization and may be used in image-guided surgery to ensure complete resection of tumor tissue. Here, we evaluated the potential of dual-modality imaging of prostate cancer with the monoclonal antibody D2B, directed against an extracellular domain of prostate-specific membrane antigen (PSMA). For these studies, D2B was labeled both with (111)In and with the NIRF dye IRDye800CW.
D2B was conjugated with N-hydroxysuccinimide-IRDye800CW and p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (ITC-DTPA) and subsequently radiolabeled with (111)In. For biodistribution and NIRF imaging, (111)In-DTPA-D2B-IRDye800CW (2 μg, 0.55 MBq/mouse) was injected intravenously into BALB/c nude mice with subcutaneous PSMA-expressing LNCaP tumors (right flank) and PSMA-negative PC3 tumors (left flank). The biodistribution was determined at 1, 2, 3, and 7 d after injection. In addition, micro-SPECT/CT and NIRF imaging with (111)In-DTPA-D2B-IRDye800CW (3 μg, 8.5 MBq/mouse) was performed on mice with intraperitoneally growing LS174T-PSMA tumors.
(111)In-DTPA-D2B-IRDye800CW specifically accumulated in subcutaneous PSMA-positive LNCaP tumors (45.8 ± 8.0 percentage injected dose per gram at 168 h after injection), whereas uptake in subcutaneous PSMA-negative PC3 tumors was significantly lower (6.6 ± 1.3 percentage injected dose per gram at 168 h after injection). Intraperitoneal LS174T-PSMA tumors could be visualized specifically with both micro-SPECT/CT and NIRF imaging at 2 d after injection, and the feasibility of image-guided resection of intraperitoneal tumors was demonstrated in this model.
Dual-labeled (111)In-DTPA-D2B-IRDye800CW enables specific and sensitive detection of prostate cancer lesions in vivo with micro-SPECT/CT and NIRF imaging. In addition to preoperative micro-SPECT/CT imaging to detect tumors, NIRF imaging enables image-guided surgical resection. These preclinical findings warrant clinical studies with (111)In-DTPA-D2B-IRDye800CW to improve tumor detection and resection in prostate cancer patients.
评估针对前列腺特异性膜抗原（PSMA）细胞外域的单克隆抗体 D2B 进行前列腺癌的双模态成像的潜力。为此，我们将 D2B 与 N-羟基琥珀酰亚胺-IRDye800CW 以及 p-异硫氰酸苄基-二乙三胺五乙酸（ITC-DTPA）偶联，并随后用（111）In 进行放射性标记。用于生物分布和近红外荧光（NIRF）成像，将（111）In-DTPA-D2B-IRDye800CW（2μg，0.55MBq/只）静脉内注射到皮下表达 PSMA 的 LNCaP 肿瘤（右侧）和 PSMA 阴性 PC3 肿瘤（左侧）的 BALB/c 裸鼠中。在注射后 1、2、3 和 7d 测定生物分布。此外，用（111）In-DTPA-D2B-IRDye800CW（3μg，8.5MBq/只）对腹腔生长的 LS174T-PSMA 肿瘤的小鼠进行 micro-SPECT/CT 和 NIRF 成像。
