AIDS Imaging Research Section, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
AIDS Imaging Research Section, Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
Eur J Nucl Med Mol Imaging. 2022 Dec;50(1):14-26. doi: 10.1007/s00259-022-05940-4. Epub 2022 Aug 27.
Previous SPECT and PET semi-quantitative in vivo imaging studies in monkeys have demonstrated specific uptake of radiolabeled rhesus recombinant anti-CD4 monoclonal antibody fragment CD4R1-F(ab΄) in the spleen and clusters of lymph nodes (LNs) but yielded conflicting results of imaging the gut CD4 + T-cell pool. Here, using PET dynamic imaging with kinetic analysis, we performed a fully quantitative CD4 imaging in rhesus macaques.
The biodistributions of [Zr]Zr-CD4R1-F(ab΄) and/or of [Zr]Zr-ibalizumab were performed with static PET scans up to 144 h (6 days) post-injection in 18 rhesus macaques with peripheral blood CD4 + T cells/μl ranging from ~ 20 to 2400. Fully quantitative analysis with a 4-h dynamic scan, arterial sampling, metabolite evaluation, and model fitting was performed in three immunocompetent monkeys to estimate the binding potential of CD4 receptors in the LNs, spleen, and gut.
The biodistributions of [Zr]Zr-CD4R1-F(ab΄) and [Zr]Zr-ibalizumab were similar in lymphoid tissues with a clear delineation of the CD4 pool in the LNs and spleen and a significant difference in lymphoid tissue uptake between immunocompetent and immunocompromised macaques. Consistent with our previous SPECT imaging of [Tc]Tc-CD4R1-F(ab΄), the [Zr]Zr-CD4R1-F(ab΄) and [Zr]Zr-Ibalizumab uptakes in the gut were low and not different between uninfected and SIV-infected CD4-depleted monkeys. Ex vivo studies of large and small intestines confirmed the in vivo images.
The majority of specific binding to CD4 + tissue was localized to LNs and spleen with minimal uptake in the gut. Binding potential derived from fully quantitative studies revealed that the contribution of the gut is lower than the spleen's contribution to the total body CD4 pool.
先前的 SPECT 和 PET 半定量体内成像研究表明，放射性标记的恒河猴重组抗 CD4 单克隆抗体片段 CD4R1-F(ab')在脾脏和淋巴结（LN）中具有特异性摄取，但对肠道 CD4+T 细胞池的成像结果存在冲突。在这里，我们使用 PET 动态成像和动力学分析，对恒河猴进行了完全定量的 CD4 成像。
在 18 只外周血 CD4+T 细胞/μl 范围从~20 到 2400 的恒河猴中，通过静态 PET 扫描在注射后长达 144 小时（6 天）进行[Zr]Zr-CD4R1-F(ab')和/或[Zr]Zr-ibalizumab 的生物分布。在 3 只免疫功能正常的猴子中进行 4 小时的动态扫描、动脉采样、代谢物评估和模型拟合的完全定量分析，以估计 LN、脾脏和肠道中 CD4 受体的结合潜力。
[Zr]Zr-CD4R1-F(ab')和[Zr]Zr-ibalizumab 的生物分布在淋巴组织中相似，LN 和脾脏中 CD4 池清晰，免疫功能正常和免疫功能低下的猴子之间的淋巴组织摄取有明显差异。与我们之前 SPECT 成像的[Tc]Tc-CD4R1-F(ab')一致，肠道中[Zr]Zr-CD4R1-F(ab')和[Zr]Zr-Ibalizumab 的摄取量在未感染和 SIV 感染的 CD4 耗竭猴子之间较低且无差异。大、小肠的离体研究证实了体内图像。
大多数对 CD4+组织的特异性结合被定位到 LN 和脾脏，肠道摄取量较少。完全定量研究得出的结合潜力表明，肠道的贡献低于脾脏对全身 CD4 池的贡献。
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