The rapid developments in non-invasive approaches to cancer detection now afford remarkable contrasts between cancers and normal tissues. Molecular beacons studied in four cooperating laboratories identify tumor specific enzymes and receptors which are used to bind, to alter the structures, etc. of delivery vehicles so that fluorescent signals are accumulated or converted from quenched to radiant forms. Tumors are also distinguished by metabolic parameters that can be distinguished by intrinsic signals of mitochondrial origin, NADH and flavoprotein and by a novel intrinsic beacon, fluorescent glucose. Angiogenesis is a third key indicator of tumorigenesis and is evaluated by quantitation of the hemoglobin content. This application proposes the high resolution co-localization and quantitation of these tumor markers in the same pixel of the tumor 3-D image, and thereby an objective test of their efficacy in cancer detection. The localization of well known metabolic signals of cancer and site directed molecular beacons require images at cellular resolution in solid tissues with preservation of metabolic state, glucose uptake and Hb concentrations and at the same time image specific tissue markers of cancer in several cm depths. This is a formidable task and one which at present requires invasive freeze trapping, in order to avoid motion artifacts and requires low temperatures to trap metabolic activities and to enhance absorption bands and fluorescence quantum yields. The functional diagram of Fig. 8 illustrates our plan to provide a complete evaluation of tumor characteristics of hypermetabolism, angiogenesis and glucose uptake (metabolic images) and cancer identification by the molecular beacons. The diagram demonstrates innovative instrument development of a Multi-wavelength Multi-channel Fluorescence/Absorption Imager for high resolution cancer detection in tissues.
The 40x40x10 micron pixel of 3D resolution of over 4 specific tumor characteristics creates a unique niche in cancer detection of animal models and of biopsy material for human cancers and is expected to afford a high throughput customated device and is expected to open a market niche in detection of early cancers in animal models (Phase I) and eventually (Phase II) in biopsy material.
