Background Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging are endowed with high sensitivity to detect tumor lesions in vivo. The combination of these modalities using dual-labeled antibodies may allow both pre- and intra-operative tumor localization as well as real-time image-guided surgery to ensure complete resection of tumor tissue. Objective To demonstrate the proof-of-principle of dual-modality imaging of prostate cancer with the monoclonal anti prostate-specific-membrane-antigen (PSMA) antibody D2B labeled with both 111In and the near-infrared fluorescent dye IRDye800CW. Design and settings D2B was conjugated with NHS-IRDye800CW and ITC-DTPA and subsequently radiolabeled with 111In. For biodistribution and NIRF imaging studies, 111In-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 days after injection. In addition, microSPECT/CT and NIRF imaging with 111In-DTPA-D2B-IRDye800CW (3 µg, 8.5 MBq/mouse) was performed in mice with intraperitoneally growing LS174T-PSMA tumor nodules. Intervention Tumor resection guided by dual-modality microSPECT/CT and NIRF imaging. Outcome measurements and statistical analysis Visualization of tumor nodules using microSPECT/CT and NIRF imaging for image guided surgery. Results and limitations 111In-DTPA-D2B-IRDye800CW specifically accumulated in the s.c. PSMA-positive LNCaP tumors (45.8 ± 8.0 %ID/g at 168h p.i.), while tumor uptake in PSMA-negative PC3 xenografts was significantly lower (6.6 ± 1.3 %ID/g at 168h p.i.). Intraperitoneal LS174T-PSMA tumors could be visualized specifically with both microSPECT/CT and NIRF imaging at 2 days p.i., showing the feasibility of image-guided resection of i.p. tumors. Conclusions Dual-label 111In-DTPA-D2B-IRDye800CW can be used for specific and sensitive detection of prostate cancer lesions in vivo with microSPECT/CT and NIRF imaging. In addition to pre-operative microSPECT/CT imaging to detect tumor lesions, NIRF imaging enables image-guided surgical resection. These preclinical findings warrant future clinical studies with 111In-DTPA-D2B- IRDye800CW to improve tumor detection and resection in prostate cancer patients.
Dual-modality image-guided surgery of prostate cancer with a radiolabeled fluorescent anti-PSMA monoclonal antibody
FRACASSO, Giulio;COLOMBATTI, Marco;
2014-01-01
Abstract
Background Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging are endowed with high sensitivity to detect tumor lesions in vivo. The combination of these modalities using dual-labeled antibodies may allow both pre- and intra-operative tumor localization as well as real-time image-guided surgery to ensure complete resection of tumor tissue. Objective To demonstrate the proof-of-principle of dual-modality imaging of prostate cancer with the monoclonal anti prostate-specific-membrane-antigen (PSMA) antibody D2B labeled with both 111In and the near-infrared fluorescent dye IRDye800CW. Design and settings D2B was conjugated with NHS-IRDye800CW and ITC-DTPA and subsequently radiolabeled with 111In. For biodistribution and NIRF imaging studies, 111In-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 days after injection. In addition, microSPECT/CT and NIRF imaging with 111In-DTPA-D2B-IRDye800CW (3 µg, 8.5 MBq/mouse) was performed in mice with intraperitoneally growing LS174T-PSMA tumor nodules. Intervention Tumor resection guided by dual-modality microSPECT/CT and NIRF imaging. Outcome measurements and statistical analysis Visualization of tumor nodules using microSPECT/CT and NIRF imaging for image guided surgery. Results and limitations 111In-DTPA-D2B-IRDye800CW specifically accumulated in the s.c. PSMA-positive LNCaP tumors (45.8 ± 8.0 %ID/g at 168h p.i.), while tumor uptake in PSMA-negative PC3 xenografts was significantly lower (6.6 ± 1.3 %ID/g at 168h p.i.). Intraperitoneal LS174T-PSMA tumors could be visualized specifically with both microSPECT/CT and NIRF imaging at 2 days p.i., showing the feasibility of image-guided resection of i.p. tumors. Conclusions Dual-label 111In-DTPA-D2B-IRDye800CW can be used for specific and sensitive detection of prostate cancer lesions in vivo with microSPECT/CT and NIRF imaging. In addition to pre-operative microSPECT/CT imaging to detect tumor lesions, NIRF imaging enables image-guided surgical resection. These preclinical findings warrant future clinical studies with 111In-DTPA-D2B- IRDye800CW to improve tumor detection and resection in prostate cancer patients.
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