Dual-Modality Image-Guided Surgery of Prostate Cancer with a Radiolabeled Fluorescent Anti-PSMA Monoclonal Antibody

Lütje, Susanne; Rijpkema, Mark; Franssen, Gerben M.; Fracasso, Giulio; Helfrich, Wijnand; Eek, Annemarie; Oyen, Wim J.G.; Colombatti, Marco; Boerman, Otto C.

doi:10.2967/jnumed.114.138180

Cited by 82 publications

(90 citation statements)

References 22 publications

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“…NIRF imaging is a sensitive technique that may be exploited to improve visualization of small to microscopic malignant lesions and potentially of positive resection margins during surgery. So far, several preclinical studies have evaluated methods to intraoperatively visualize tumor tissue and resection margins in prostate cancer (12)(13)(14). Targeted approaches using antibodies or peptides are particularly promising to apply dual-modality imaging.…”

Section: Discussionmentioning

confidence: 99%

Pretargeted Dual-Modality Immuno-SPECT and Near-Infrared Fluorescence Imaging for Image-Guided Surgery of Prostate Cancer

et al. 2014

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Radical removal of malignant lesions may be improved using tumor-targeted dual-modality probes that contain both a radiotracer and a fluorescent label to allow for enhanced intraoperative delineation of tumor resection margins. Because pretargeting strategies yield high signal-to-background ratios, we evaluated the feasibility of a pretargeting strategy for intraoperative imaging in prostate cancer using an anti-TROP-2 x anti-HSG bispecific antibody (TF12) in conjunction with the dual-labeled diHSG peptide (RDC018) equipped with both a DOTA chelate for radiolabeling purposes and a fluorophore (IRdye800CW) to allow near-infrared optical imaging. Nude mice implanted s.c. with TROP-2-expressing PC3 human prostate tumor cells or with PC3 metastases in the scapular and suprarenal region were injected i.v. with 1 mg of TF12 and, after 16 hours of tumor accumulation and blood clearance, were subsequently injected with 10 MBq, 0.2 nmol/mouse of either 111 In-RDC018 or 111 In-IMP288 as a control. Two hours after injection, both microSPECT/CT and fluorescence images were acquired, both before and after resection of the tumor nodules. After image acquisition, the biodistribution of 111 In-RDC018 and 111 In-IMP288 was determined and tumors were analyzed immunohistochemically. The biodistribution of the dual-label RDC018 showed specific accumulation in the TROP-2-expressing PC3 tumors (12.4 AE 3.7% ID/g at 2 hours postinjection), comparable with 111 In-IMP288 (9.1 AE 2.8% ID/g at 2 hours postinjection). MicroSPECT/CT and near-infrared fluorescence (NIRF) imaging confirmed this TROP-2-specific uptake of the dual-label 111 In-RDC018 in both the s.c. and metastatic growing tumor model. In addition, PC3 metastases could be visualized preoperatively with SPECT/CT and could subsequently be resected by imageguided surgery using intraoperative NIRF imaging, showing the preclinical feasibility of pretargeted dualmodality imaging approach in prostate cancer. Cancer Res; 74(21); 6216-23. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

Pretargeted Dual-Modality Immuno-SPECT and Near-Infrared Fluorescence Imaging for Image-Guided Surgery of Prostate Cancer

et al. 2014

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“…Recent examples include dual-labeled antibodies such as probes (anti-EpCAM, anti-CEA, anti-PSMA) with dual PET and optical imaging functions, for imaging prostate cancer pre- and intra-surgery, and set the stage for clinical translation (Figure 5) (Hall et al, 2012; Lütje et al, 2014b; Rijpkema et al, 2014). …”

Section: Development Of Antibodies and Fragments For In Vivo Imagingmentioning

confidence: 99%

In vivo imaging with antibodies and engineered fragments

Freise

2015

Molecular Immunology

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Antibodies have clearly demonstrated their utility as therapeutics, providing highly selective and effective drugs to treat diseases in oncology, hematology, cardiology, immunology and autoimmunity, and infectious diseases. More recently, a pressing need for equally specific and targeted imaging agents for assessing disease in vivo, in preclinical models and patients, has emerged. This review summarizes strategies for developing and optimizing antibodies as targeted probes for use in non-invasive imaging using radioactive, optical, magnetic resonance, and ultrasound approaches. Recent advances in engineered antibody fragments and scaffolds, conjugation and labeling methods, and multimodality probes are highlighted. Importantly, antibody-based imaging probes are seeing new applications in detection and quantitation of cell surface biomarkers, imaging specific responses to targeted therapies, and monitoring immune responses in oncology and other diseases. Antibody-based imaging will provide essential tools to facilitate the transition to truly precision medicine.

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“…16,17 We report the synthesis of [ 18 F]- 4 , a PSMA specific fluorophore that is visible by 18 F-PET.…”

Section: Introductionmentioning

confidence: 99%

¹⁸F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management

et al. 2018

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[18/19F]-4, an anionic GCPII/PSMA inhibitor for image-guided intervention in prostate cancer, is described. [19F]-4 is radiolabeled with a radiochemical yield that is ≥27% and a molar activity of 190 ± 50 mCi/μmol in a <1 h, one-step, aqueous isotopic exchange reaction. [19F]-4 allows PSMA expression to be imaged by fluorescence (FL) and [18F]-PET. PC3-PIP (PSMA-positive, EC50 = 6.74 ± 1.33 nM) cancers are specifically delineated in mice that bear 3 million (18 mg) PC3-PIP and PC3 (control, PSMA-negative) cells. Colocalization of [18/19F]-4 PET, fluorescence, scintillated biodistribution, and PSMA expression are observed.

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Dual-Modality Image-Guided Surgery of Prostate Cancer with a Radiolabeled Fluorescent Anti-PSMA Monoclonal Antibody

Cited by 82 publications

References 22 publications

Pretargeted Dual-Modality Immuno-SPECT and Near-Infrared Fluorescence Imaging for Image-Guided Surgery of Prostate Cancer

Pretargeted Dual-Modality Immuno-SPECT and Near-Infrared Fluorescence Imaging for Image-Guided Surgery of Prostate Cancer

In vivo imaging with antibodies and engineered fragments

¹⁸F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management

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Dual-Modality Image-Guided Surgery of Prostate Cancer with a Radiolabeled Fluorescent Anti-PSMA Monoclonal Antibody

Cited by 82 publications

References 22 publications

Pretargeted Dual-Modality Immuno-SPECT and Near-Infrared Fluorescence Imaging for Image-Guided Surgery of Prostate Cancer

Pretargeted Dual-Modality Immuno-SPECT and Near-Infrared Fluorescence Imaging for Image-Guided Surgery of Prostate Cancer

In vivo imaging with antibodies and engineered fragments

18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management

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¹⁸F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management