Aims
Tumor Paint is a peptide-fluorophore conjugate being developed as a real-time intraoperative guide for cancer surgeries. It specifically binds to cancer cells, causing the tumor tissue to fluoresce in the near-infrared range while adjacent normal tissue is not fluorescent. Use of Tumor Paint in skin cancers has the potential to assist surgeons in obtaining negative tumor margins and sparing normal surrounding tissues. Tumor Paint was tested in mouse models of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and amelanotic melanoma in order to assess imaging efficacy.
Methods
K5-Gli2:C57bl/6 albino mice (BCC model) were obtained from Dr. Allan Oseroff at the Roswell Park Cancer Institute. Pold1D400A/D400A : FVB mice (SCC model) were obtained from Dr. Bradley Preston at the University of Washington. Amelanotic melanoma xenografts were prepared by injecting 106 A375 cells into the flanks of Nu/Nu mice. Tumor Paint (2 nmole) was administered to 3 tumor-bearing and 2 control mice for each model via tail vein injection. Mice were imaged 3-4 days later using a Xenogen Spectrum imaging system. Mice were euthanized, and tumor bearing tissues were imaged separately and cancer specificity assessed histologically.
Results
Cancerous foci were visible on the ears of 3 K5-Gli2 mice and 2 Pold1D400A/D400A mice. Near-infrared imaging showed Tumor Paint staining in 5/5 ears with tumors, and in A375 flank tumors. Mice that did not have visible lesions did not show specific fluorescence. H&E staining showed cancerous histopathologic changes corresponding to Tumor Paint signal.
Conclusions
Non-melanotic skin cancers can be recognized and illuminated using Tumor Paint. These lesions are often more difficult to detect than melanotic melanomas. This non-clinical study supports future evaluation of Tumor Paint for skin cancer resection, margin evaluation, and perhaps screening in high risk individuals.