Abstract 4936: Tumor PaintTM technology detects naturally occurring solid tumors in dogs

Abstract

Abstract Tumor PaintTM technology is designed to provide real-time visualization of tumors during surgery at improved resolution over existing methods. BLZ-100 is a Tumor Paint product consisting of a chlorotoxin (CTX) peptide conjugated to a near-infrared (NIR) fluorophore that is being advanced toward clinical studies. CTX-based Tumor Paint products have been shown to illuminate a broad range of cancers in mouse models. To facilitate clinical translation, a preclinical feasibility study was conducted in dogs with naturally occurring solid tumors. Many types of canine tumors resemble human disease, including sarcomas, mammary and lung cancers, mucosal squamous cell cancers, and gliomas. The diversity of tumor size and type, surrounding tissue, and patient body mass provides a model that is superior to the mouse in predicting the clinical characteristics of BLZ-100, including tumor penetration, background staining, and effective imaging dose. Twenty-seven dogs were given BLZ-100 intravenously 24 - 48 hours before surgery. Doses, normalized to body surface area (mg/m2), were 0.25 - 0.8 (7 dogs), 0.8 - 1.2 (15 dogs) and 1.2 - 1.6 (5 dogs). Tumor types were sarcoma, adenocarcinoma, mastocytoma, squamous cell carcinoma, and meningioma. Dogs received standard of care including tumor resection with intent to control or cure local disease. Excised tissues were imaged using the IVIS Spectrum (Caliper) and the Odyssey NIR scanner (Li-Cor) to determine overall signal in tumor and gross tumor to normal ratios. Tissues were then embedded in OCT, sectioned on a cryostat, and scanned on the Odyssey. Serial sections were stained with H&E, and comparison with the fluorescence scans was used to validate the specificity of BLZ-100 for tumor tissue. Ex vivo imaging data showed maximal tumor fluorescence at doses above 0.9 mg/m2. In dogs treated with 0.8 mg/m2 or higher (20 dogs in total), ratios of fluorescence in tumour to normal surrounding tissue ranged from <1 (no specific signal, 2 dogs) to >200, with good differentiation in several tumor types including meningioma, carcinomas (lung, thyroid, and mammary), and sarcomas. Highest signals and gross tumor to background ratios were seen in a subset of soft tissue sarcomas, suggesting preferential uptake of the conjugate in these tumor types. Histologic analysis of these cases showed 95% sensitivity and 85% specificity. Intraoperative imaging was conducted in several cases, using a prototype open NIR imaging device. These cases showed good contrast between gross tumors and surrounding structures, detection of tumor through 0.5 cm of normal fatty tissue, and low background in tissues such as fat and muscle. The information obtained in this study provides data that will be valuable in clinical translation of BLZ-100. This project was funded in whole with Federal funds from National Cancer Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN2612012000054C. Citation Format: William S. Dernell, Janean Fidel, Katie Kennedy, Stacey Hansen, Valorie Wiss, Mark Stroud, Julia E. Parrish-Novak. Tumor PaintTM technology detects naturally occurring solid tumors in dogs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4936. doi:10.1158/1538-7445.AM2014-4936