The maturation of molecular imaging of cancers emphasizes the high tumor tissue ratios above ten which, when approved by FDA, are expected to revolutionize the sensitivity/specificity of, for example, breast and prostate cancer detection. The development of molecular beacons from collaborating laboratories has provided the two key types of beacons, one being the affinity binding, for example somatostatin, LDL, folate and the stealth or silent beacons (Cathepsin B, etc.) that depend upon recognition and unmasking of the fluorochrome attached to the beacon. Most recently, a fluorescent glucose generally applicable to all rapidly growing cancers has incorporated a NIR fluorochrome. While the NADH and flavoprotein signals are the gold standard of recognition of cancer by the greater glycolytic flow and enhanced reduction state of the tumor, these markers can be greatly enhanced by multi-photon technologies. In addition, the time shared wavelengths characteristically include reflectance spectophotometry of deoxy and total hemoglobin affording a direct links to hypermetabolism and angiogenesis. However, the most important aspect of the technology is its 3-D capability since ice crystal formation which characterizes the freeze trap state, impedes penetration of light through the highly scattering crystal matrix is very limited and fluorescent signals deeper than tens of microns do not interfere with planar images. Finally, fiber optic technology will permit reduction of the size of the voxel from 50 x 50 x 10 to 30 x 30 x 10 mu or even smaller depending upon the light guide construction. As a result of Phase I funding, a greatly improved, simplified and more economical design of the 3-D light pen imager has been completed. A vastly improved system which employs a time multiplex LED source system and silicon diode detector system which will permit a much greater throughput because of the increased duty cycle from roughly 20% to 75%. The operation is automatic and its authenticity is validated by the experiments carried out under Phase I support. Finally, a timetable and milestone exhibit assures production of the second phase model within 8 months at the funding of Phase II and exhaustive validation tests and tech transfer to occur in the remaining 16 months of the Phase II study.
