AIDS Imaging Research—Integrated Research Facility at Fort Detrick

As part of model development, the team conducts in vitro and in vivo experimental testing of novel radiolabeled probes for single-photon emission computed tomography (SPECT) and positron emission tomography–computed tomography (PET/CT) imaging of SIV/SHIV-exposed nonhuman primates for application in the following areas:

• Whole-body T-cell pool
• Immune activation
• Antiviral drug-delivery strategies (such as, lipid-based nanoparticles) and whole-body pharmacokinetics
• Viral replication in anatomic compartments
• Neuroinflammation

The AIRS program is tied to the Mathematical Biology Section of the Biostatistics Research Branch (in the DRC) focused on integrating mathematical modeling with experimental data to investigate the within-host dynamics of lentiviral infections.
 

Whole-body CD4 pool imaging in unexposed and SIV-exposed rhesus monkeys.

Images acquired 48 hours after radiotracer injection show high levels of radiotracer uptake (SUV rainbow scale) in clusters of lymph nodes and the spleen of unexposed animals, i.e., in lymphoid organs with the highest concentrations of CD4 receptors per unit volume of tissue. A dramatic decrease in radiotracer uptake was observed in the same organs of the SIV-exposed monkey as well as in the same organs of an unexposed animal co-injected with excess unlabeled probe. Radiotracer uptake in the bowel is at background level of all images.

Credit: NIH Animal Center

• PET and CT image acquisition and quantitative analyses to quantify changes in lymphoid organs function after SIV/SHIV exposure in nonhuman primates
• SPECT and CT imaging protocols to evaluate SIV/SHIV-induced disease progression
• Radiosynthesis of PET and SPECT molecular imaging agents to probe-specific processes related to host immune responses and/or organ pathophysiology
• Radio-high-performance liquid chromatography (radio-HPLC) capabilities to study probe stability
• In vitro testing of radiolabeled probes in cell lines and primary cells
• Autoradiography studies of tissue sections from SIV/SHIV-exposed nonhuman primates
• Dedicated commercial software for quantitative image analyses
• Access to NIH Imaging Probe Development Center development or manufacture of imaging probes
• Imaging to evaluate pre-clinical and translational pathophysiological SIV/SHIV-induced disease mechanisms and processes
• Imaging tools to study the penetration of antiretroviral therapies in tissues and strategies to prolong tissue antiviral drugs retention through nanoparticle technologies

• Using imaging to detect biomarkers for lentiviral disease 

Whole-body immune activation imaging during acute and chronic SIV infection of rhesus monkeys (non-natural hosts) and green monkeys (natural hosts).

Images acquired 1 hour after radiotracer injection show increases in radiotracer uptake (SUV rainbow scale) in clusters of lymph nodes and the spleen of both species. Radiotracer uptake in the bowel is unchanged during the course of the disease in both species.

Credit: NIH Animal Center

Kim I., Srinivasula S., DeGrange P., Long B., Jang H., Carrasquillo J.A., Lane H.C., Di Mascio M. Quantitative PET imaging of the CD4 pool in nonhuman primates. Eur. J. Nucl. Med. & Mol. Imaging, 2022 Aug 27:50 (14-26).

Sinharay S., Srinivasula S., Schreiber-Stainthorp W., Shah S., Degrange P., Bonvillain A., Wang J., Dodd L., Carrasquillo J.A., Hammoud D.A., Di Mascio M. Monitoring Immune Activation with Whole-Body Fluorodeoxyglucose–Positron-Emission Tomography in Simian Immunodeficiency Virus–Infected Rhesus Macaques. ImmunoHorizons, 2021 July 5: (7):557-567.

Di Mascio M., Lifson J.J., Srinivasula S., DeGrange P., Keele B., Proschan M., Lane H.C., Fauci A.S. Evaluation of an antibody to Alpha4Beta7 in the control of SIV infection. Science, 2019 Sep 6: 354(6457):1025-1029.

Srinivasula S., Gabriel E., Kim I., DeGrange P., St Claire A., Mallow C., Donahue R.E., Paik C., Lane H.C., Di Mascio M. CD4+ levels control the odds of induction of humoral immune responses to tracer doses of therapeutic antibodies. PLOS One PLoS One. 2017 Nov 9;12(11): e0187912.

Donahue RE, Srinivasula S, Uchida N, Kim I, St Claire A, Duralde G, DeGrange P, St Claire M, Reba RC, Bonifacino AC, Krouse AE, Metzger ME, Paik CH, Lane HC, Tisdale JF, Di Mascio M. Discordance in lymphoid tissue recovery following stem cell transplantation in rhesus macaques: an in vivo imaging study.Blood 2015 Dec 10: 126(24):2632-41.

Deeks SG, Autran B, Berkhout B, Benkirane M, Cairns S, Chomont N, Chun TW, Churchill M, Di Mascio M., Katlama C, Lafeuillade A, Landay A, Lederman M, Lewin SR, Maldarelli F, Margolis D, Markowitz M, Martinez-Picado J, Mullins JI, Mellors J, Moreno S, O'Doherty U, Palmer S, Penicaud MC, Peterlin M, Poli G, Routy JP, Rouzioux C, Silvestri G, Stevenson M, Telenti A, Lint CV, Verdin E, Woolfrey A, Zaia J, Barré-Sinoussi F. Towards an HIV cure: a global scientific strategy.The International AIDS Society Scientific Working Group on HIV Cure. Nat Rev Immunol. 2012 Jul 20:12(8):607-614.

National Institutes of Health Animal Center

Michele Di Mascio, Ph.D.
Chief, AIDS Imaging Research Section
Chief, Mathematical Biology Section