Core B serves as an integrated bridge in cross validating the results obtained in projects 1 and 2 (H. Gendelman and H. Fox). The core will provide bioimaging support to assess nanoformulated antiretroviral drug (nanoART) tissue delivery using magnetic resonance imaging (MRI) and single photon emission/X-ray computed tomography (SPECT/CT). The core will support diagnostic and pharmacokinetic studies in animal models (rodent and rhesus macaques) of HlV-1- and SlV-associated diseases. Magnetic resonance spectroscopy (MRS) and SPECT will be used to pinpoint drug biodistribution and therapeutic responses. MRI and MRS methods proposed in support of the projects include tracking of magnetically and radiolabeled cells, quantitative diffusion tensor imaging, quantitative proton magnetic resonance spectroscopy for imaging cell migration and assess nanotoxicologies and drug availability. The bioimaging core has four principal goals: (1) to use MRI and SPECT/CT for cell and nanotracking to determine nanoparticle (NP) and NPcarried cell biodistribution;(2) to determine the kinetics of cell and particle entry into viral sanctuaries including the nervous system by non-invasively following disease related metabolic and physiological alterations;(3) to elucidate disease related alterations using MRI coregistered to histopathology;and (4) to improve diagnosis and therapeutic monitoring in rodent and monkey models of HlV-1 associated disease. Most importantly, the works proposed serve to bring the projects and core C (C. Fletcher) into an integrated focus by serving to complement ongoing pharmacokinetic studies for cell-based drug delivery.
The officacy of antiretroviral medicines in reducing disease morbidity and morality is unprecedented. Treatments lead to sustained viral suppression and protection of adaptive immunity over prolonged time periods in virus-infected patients. Nonetheless, an important issue rests in adherence to often complex dosing regimens in patients who abuse drugs. Sustained release nanoformulations of ART (nanoART) can serve to overcome this issue and lead to improved treatment outcomes for HIV/AIDS. This bioimaging core serves to monitor treatment efficacy of nanoART by providing cross-validation of drug and cell-based drug distributions in animal models of HIV and are directly applicable to future human studies.
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