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If you think about Nuclear Medicine, the first thing that comes to mind is probably radioactivity. And indeed, our department uses radionuclides for tumor imaging and therapy. However, less well-known is that we also use laser-light and photosensitizers for tumor treatment.
Photosensitizers are molecules that can be activated with light of a specific wavelength, upon which they induce the formation of reactive oxygen species. These species lead to cell death, which is very useful to eliminate tumor cells in a controlled manner. This method is called photodynamic therapy.
At our department, we first couple photosensitizers to tumor targeting molecules. Examples are peptides targeting glucagon like peptide-1 receptor (GLP1R) for treatment of insulinoma, antibodies targeting carcinoembryonic antigen (CEA) for treatment of colon cancer and designed ankyrin repeat proteins (DARPins) targeting epithelial cell adhesion molecule (EpCAM) for treatment of ovarian cancer. These tumor-targeting molecules are optimized so that they can be used for targeted photodynamic therapy in preclinical tumor models.
Besides direct treatment of tumor cells, we are also investigating the effect of elimination of the cancer associated fibroblast with fibroblast activation protein (FAP) targeted photodynamic therapy, and its effects on the tumor microenvironment.
In our latest published articles, we combined the best of the nuclear and the optical world by attaching both a radionuclide and a photosensitizer to a prostate specific membrane antigen (PSMA) binding peptide1 and an epidermal growth factor receptor (EGFR) binding nanobody2. In this way, we can 1) preoperatively detect the tumor using SPECT scans, 2) intraoperatively be guided to the tumor through radioguidance, 3) use fluorescence imaging for precise intraoperative tumor localization and 4) illuminate the surgical cavity or tumor lesion to ablate tumor cells. This multimodal approach will help the surgeon to detect and completely resect the tumor, thereby decreasing the chance of tumor recurrence and improving prognosis of cancer patients.
To learn more about our colleague's research, every writer will nominate a colleague from another department. Sanne nominates Lara Konijnenberg. We're really curious about your project!
Publication
1 Derks YHW, Rijpkema M, Amatdjais-Groenen HIV, Kip A, Franssen GM, Sedelaar JPM, Somford DM, Simons M, Laverman P, Gotthardt M, Löwik DWPM, Lütje S, Heskamp S. Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer. Theranostics. 2021 Jan 1;11(4):1527-1541. doi: 10.7150/thno.52166
2 Renard E, Collado Camps E, Canovas C, Kip A, Gotthardt M, Rijpkema M, Denat F, Goncalves V, van Lith SAM. Site-Specific Dual-Labeling of a VHH with a Chelator and a Photosensitizer for Nuclear Imaging and Targeted Photodynamic Therapy of EGFR-Positive Tumors. Cancers (Basel) 2021 Jan 23;13(3):428. doi: 10.3390/cancers13030428.
