Dual-labeled compounds for intraoperative dual modality imaging

For many types of cancer, surgical resection is the best or only chance for cure. Incomplete excision of tumor tissue however, negatively affects the prognosis of the patient. In many cases, the presence of (microscopic) residual tumor tissue at the resection margins is a direct predictor of patient survival. The completeness of tumor removal during surgery is dependent on the surgeon’s ability to differentiate tumor from normal tissue. Ideally, surgeons could use real-time information to detect tumors or positive resection margins during surgery. For this purpose intraoperative visualization techniques are commonly applied in different types of cancer.

To accomplish radical excision of tumor tissue, radiotracers can be used that target tumor tissue and can be detected using a gamma probe during surgery. Yet, this technique cannot provide a precise delineation of the tumor and resection margins. The addition of a fluorescent label could help to overcome this limitation. Intraoperative fluorescence imaging could allow accurate real-time tumor delineation, but the penetration depth of emitted light in biological tissue is limited. So, a powerful synergy can be achieved by combining radiotracers for the detection of tumor tissue, and optical tracers for subsequent accurate delineation of tumors.

We are working on the development of new dual-labeled tracers and preclinical studies to show the potential of this approach for intraoperative detection of tumor lesions. For example, the feasibility of radionuclide detection and fluorescence guided surgery using dual-labeled anti-CEA monoclonal antibodies in a CEA-expressing tumor model was demonstrated using the anti-CEA antibody MN-14 tagged with both a radioactive (111In) and a fluorescent label (IRdye800CW).

Currently, we are implementing this into the clinic. For example, in patients with renal cell carcinoma, intraoperative dual-modality imaging is applied using girentuximab labeled with 111In and IRDye800CW. The results show that both radionuclide detection and fluorescence imaging provide useful information to improve localization of tumors and radical excision of tumor tissue.


People

In the press

Publications

  • C.H.J. Muselaers, M. Rijpkema, D.L. Bos, J.F. Langenhuijsen, W.J.G. Oyen, P.F.A. Mulders, E. Oosterwijk and O.C. Boerman. "Radionuclide and Fluorescence Imaging of Clear Cell Renal Cell Carcinoma Using Dual Labeled Anti-Carbonic Anhydrase IX Antibody G250.", J Urol 2015;194(2):532-538. Abstract DOI PMID

  • S.Y.A. Terry, M. Rijpkema, K. Abiraj, W.T. van der Graaf, W.J. Oyen and O.C. Boerman. "Radiolabeled imaging probes targeting angiogenesis for personalized medicine", Curr Pharm Des 2014;20:2293-2307. Abstract PMID

  • S. Lütje, M. Rijpkema, D.M. Goldenberg, C.M. van Rij, R.M. Sharkey, W.J. McBride, G.M. Franssen, C. Frielink, W. Helfrich, W.J.G. Oyen and O.C. Boerman. "Pretargeted Dual-Modality Immuno-SPECT and Near-Infrared Fluorescence Imaging for Image-Guided Surgery of Prostate Cancer", Cancer Research 2014;74:6216-6223. Abstract/PDF DOI PMID

  • S. Lütje, M. Rijpkema, G.M. Franssen, G. Fracasso, W. Helfrich, A. Eek, W.J. Oyen, M. Colombatti and O.C. Boerman. "Dual-Modality Image-Guided Surgery of Prostate Cancer with a Radiolabeled Fluorescent Anti-PSMA Monoclonal Antibody", Journal of Nuclear Medicine 2014;55:995-1001. Abstract/PDF DOI PMID

  • S. Lütje, M. Rijpkema, W. Helfrich, W.J.G. Oyen and O.C. Boerman. "Targeted Radionuclide and Fluorescence Dual-modality Imaging of Cancer: Preclinical Advances and Clinical Translation", Molecular Imaging and Biology 2014;16:747-755. Abstract/PDF DOI PMID

  • C.H.J. Muselaers, A.B. Stillebroer, M. Rijpkema, G.M. Franssen, E. Oosterwijk, P.F.A. Mulders, W.J.G. Oyen and O.C. Boerman. "Optical Imaging of Renal Cell Carcinoma with Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab", Journal of Nuclear Medicine 2014;55:1035-1040. Abstract/PDF DOI PMID

  • M. Rijpkema, W.J. Oyen, D. Bos, G.M. Franssen, D.M. Goldenberg and O.C. Boerman. "SPECT- and Fluorescence Image-Guided Surgery Using a Dual-Labeled Carcinoembryonic Antigen-Targeting Antibody", Journal of Nuclear Medicine 2014;55:1519-1524. Abstract/PDF DOI PMID