A major goal in AIDS research is the development of new markers to monitor HIV-1 disease progression and drug therapy, particularly during the clinically latent period. During this period, HIV-1 accumulates and actively replicates in lymphoid/organs. Development of an imaging agent for HIV-1 disease would provide a non-invasive technique to localize and quantitate HIV-1 virions and productively infected cells in the body. In the Phase I study, it was demonstrated that two radioiodinated CD4- immunoglobulin chimeric proteins, CD4-gamma2 and CD4-IgG2, bind with high affinity and specificity to the envelope glycoprotein from a laboratory- adapted strain and a primary isolate of HIV-1. In the Phase II project, the ability of these radioimmunoconjugates to bind tissue sections from HIV-1 infected individuals will be examined. The imaging agents will be tested in a novel animal model of HIV-1 envelope glycoprotein expression - - recombinant gp120/gp41 vaccina virus-infected mice. One immunoconjugate will be selected for further studies in macaques infected with simian immunodeficiency virus (SW) or simian-human immunodeficiency virus (SHIV), and chimpanzees infected with HIV-1. Finally, methods of attaching to the immunoconjugate alternative radionuclides (99MTc or 111In) will be examined. Demonstration of in vivo 'proof-of-concept' in this Phase II project would be a critical step in the preclinical development of a commercial imaging agent for use in man.
Development of an in vivo CD4-based imaging agent for HIV-1 disease to determine the distribution and burden of HIV-1 virions and infected cells in tissues for use in staging infection and disease, determining clinical prognosis and outcome, and monitoring disease progression and drug therapy.
