Acquired immunodeficiency syndrome (AIDS) and cancer are among the most serious public health problems facing our nation today. Finding better ways to detect, treat, and reduce the transmission of these disorders are thus defined as research goals of the highest importance. This proposal is concerned with just these objectives. It involves the synthesis and study of new """"""""sapphyrins"""""""" (of general structure 1) and """"""""texaphyrins"""""""" (of general structure 2), tripyrroledimethine-derived """"""""expanded porphyrins"""""""", which on the bases of initial studies, are expected to: 1) act as improved photosensitizers for use in photoinduced exo vivo anti-HIV-1 blood purification protocols, 2) serve as the bases for developing a class of stable, nonlabile gadolinium(III)-containing complexes suitable for use in magnetic imaging (MRI) applications, and 3) allow the preparation of new bifunctional conjugates for use in the radiolabeling od monoclonal antibodies with 90Y and 111In. All synthetic aspects of the proposed projects and many of the initial chemical and photochemical screening studies will be carried out P.I. and his coworkers at The UNiversity of Texas at Austin. More specialized physical and/or biochemical studies will be carried out in collaboration with the groups of Anthony Harriman, Ph.D. (University of Texas at Austin), Dean Sherry, Ph.D. (University of Texas at Dallas), Michael F. Tweedle, Ph.D. (Squibb Medical Institute), Richard Miller, M.D. and John Leonard, Ph.D. (both of IDEC Pharmaceuticals), J. Lester Matthews, Ph.D. (Baylor Research Foundation), and Tranh Chanh, Ph.D. (Southwest Foundation for Biomedical Research).
| Young, S W; Qing, F; Harriman, A et al. (1996) Gadolinium(III) texaphyrin: a tumor selective radiation sensitizer that is detectable by MRI. Proc Natl Acad Sci U S A 93:6610-5 |
| Geraldes, C F; Sherry, A D; Vallet, P et al. (1995) Nuclear magnetic relaxation dispersion studies of water-soluble gadolinium(III)-texaphyrin complexes. J Magn Reson Imaging 5:725-9 |
| Kral, V; Brucker, E A; Hemmi, G et al. (1995) A non-ionic water-soluble pentaphyrin derivative. Synthesis and cytotoxicity. Bioorg Med Chem 3:573-8 |
| Young, S W; Sidhu, M K; Qing, F et al. (1994) Preclinical evaluation of gadolinium (III) texaphyrin complex. A new paramagnetic contrast agent for magnetic resonance imaging. Invest Radiol 29:330-8 |
| Roitman, L; Ehrenberg, B; Nitzan, Y et al. (1994) Spectroscopy and photosensitization of sapphyrins in solutions and biological membranes. Photochem Photobiol 60:421-6 |
