Noninvasive in vivo imaging of CD4 cells in simian-human immunodeficiency virus (SHIV)–infected nonhuman primates

Abstract

Since the earliest days of the HIV epidemic, the number of CD4 ؉ T cells per unit volume of blood has been recognized as a major prognostic factor for the development of AIDS in persons with HIV infection. It has also been generally accepted that approximately 2% of total body lymphocytes circulate in the blood. In the present study, we have used a nondepleting humanized anti-CD4 monoclonal antibody labeled with the gamma emitter indium-111 to visualize the CD4 ؉ T-cell pool in vivo in nonhuman primates with simian HIV infection. A strong correlation was noted between radiotracer uptake in spleen, tonsil, axillary lymph nodes, and peripheral blood CD4 T-cell counts ( ‫؍‬ 0.75, 0.93, and 0.85, respectively, P < .005). The relationship between radiotracer retention in lymphoid tissues and CD4 ؉ T-cell counts in the circulation was governed by an exponential law. These data provide an estimate for the total number of lymphocytes in the body as being between 1.9 and 2.9 ؋ 10 12 and suggest that the partition between peripheral blood and lymphoid tissue is between 0.3% and 0.5%. (Blood. 2009; 114:328-337)

Discordance in lymphoid tissue recovery following stem cell transplantation in rhesus macaques: an in vivo imaging study

“…The percentage of the labeled fragment bound to cells was .60% at 4 3 10 6 MT4 cells, and its immunoreactivity was estimated to be ;100% extrapolated under condition of excess receptor concentration based on the Lindmo method, 8 similar to the intact anti-CD4 mAbs previously described. 4 In order to demonstrate the specificity of radiotracer binding to CD4 In-DTPA-CDR-OKT4A/huIgG4. 4,9 The size-exclusion HPLC analysis of the plasma at baseline imaging showed that ;90% of the injected 99m Tc -F(ab9)2-CD4R1 remained at ;4 hours postinjection in vivo, and no evidence of formation of metabolites or catabolites, thus confirming the stability of the radiotracer in vivo (data not shown).…”

“…4 In order to demonstrate the specificity of radiotracer binding to CD4 In-DTPA-CDR-OKT4A/huIgG4. 4,9 The size-exclusion HPLC analysis of the plasma at baseline imaging showed that ;90% of the injected 99m Tc -F(ab9)2-CD4R1 remained at ;4 hours postinjection in vivo, and no evidence of formation of metabolites or catabolites, thus confirming the stability of the radiotracer in vivo (data not shown).…”

“…4 Imaging and biodistribution studies SPECT/computed tomography (CT) images were taken prior to transplant and at ;6, 30, 90, 150, 260, and 380 days post-TBI. Animals were anesthetized with ketamine (10 mg/kg), and maintained on propofol (Diprivan 10 mg/mL; initial 2.5-5 mg/kg dose given as a bolus, then 0.3-0.4 mg/kg per minute of constant IV infusion).…”

“…3 In addition, we have developed a strategy to evaluate noninvasively and in real time the contribution of the CD4 1 cell population to LTs using single-photon emission computed tomography (SPECT) imaging. 4 This technique has been used to study the relationships between the PB and LT pool of CD4 1 T cells in healthy and SIV-or simian/human immunodeficiency virus (SHIV)-infected animals. In the present study, we have used a combination of SPECT imaging and a radiotracer, The online version of this article contains a data supplement.…”

Visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging

“…Compared with PET-CT, MRI can provide higher spatial resolution at near-cellular level, but with much lower sensitivity (Lecchi et al, 2007). Previous efforts using MRI in HIV research were mostly focused on imaging the pathogenesis caused by HIV or simian immunodeficiency virus (SIV) infection in the brain of patients or experimental non-human primates (Archibald et al, 2004;Di Mascio et al, 2009;Venneti et al, 2008;Zhang & Li, 2013).…”