Quantitative PET imaging of the CD4 pool in nonhuman primates

Area of Science:

• Immunology
• Radiochemistry
• Medical Imaging

Background:

• Previous studies using SPECT and PET imaging showed specific uptake of radiolabeled anti-CD4 antibody fragments in spleen and lymph nodes (LNs) of monkeys.
• Conflicting results existed regarding the imaging of the gut CD4+ T-cell pool.

Purpose of the Study:

• To perform fully quantitative CD4 imaging in rhesus macaques using positron emission tomography (PET) dynamic imaging with kinetic analysis.
• To accurately assess the distribution and binding potential of CD4 receptors in lymphoid tissues and the gut.

Main Methods:

• Biodistribution studies of [89Zr]Zr-CD4R1-F(ab΄)2 and [89Zr]Zr-ibalizumab were conducted using static PET scans in 18 rhesus macaques.
• Fully quantitative analysis involving dynamic PET scans, arterial sampling, metabolite evaluation, and model fitting was performed in three immunocompetent monkeys.

Main Results:

• Biodistributions of both radiotracers were similar in lymphoid tissues, clearly delineating the CD4 pool in LNs and spleen.
• Significant differences in lymphoid tissue uptake were observed between immunocompetent and immunocompromised macaques.
• Uptake in the gut was low and not significantly different between uninfected and SIV-infected CD4-depleted monkeys, consistent with prior SPECT imaging.

Conclusions:

• Specific binding to CD4+ tissue was predominantly localized to LNs and spleen, with minimal uptake in the gut.
• Quantitative binding potential studies indicated that the gut contributes less to the total body CD4 pool compared to the spleen.