Human dose-escalation study of PET imaging CD8+ T-cell infiltration in solid malignancies with 68GaGa -NODAGA-SNA006

A noninvasive method for evaluating the infiltration of CD8+ T cells in tumors is urgently needed to monitor the response to immunotherapy. This study investigated the performance of a [68Ga]Ga-NODAGA-SNA006 in positron emission tomography (PET) imaging of CD8+ T cells in patients with solid malignancies.PURPOSEA noninvasive method for evaluating the infiltration of CD8+ T cells in tumors is urgently needed to monitor the response to immunotherapy. This study investigated the performance of a [68Ga]Ga-NODAGA-SNA006 in positron emission tomography (PET) imaging of CD8+ T cells in patients with solid malignancies.This human dose-escalation PET imaging study involved eleven patients (lung cancer, 8; gastric carcinoma, 1; esophageal carcinoma, 2). Approximately 150 MBq of [68Ga]Ga-NODAGA-SNA006 with varying nanobody masses (100 µg, 300 µg, 500 µg, 800 µg) was administered, and PET/computed tomography (CT) scans were performed at 15-30, 60-90 and 120 min postinjection (p.i.). Data regarding biodistribution, pharmacokinetics and radiation dosimetry were evaluated. CD8+ T-cell infiltration in biopsy samples was also measured via immunohistochemistry (IHC) for correlation analysis with the tumor uptake of [68Ga]Ga-NODAGA-SNA006 PET.METHODSThis human dose-escalation PET imaging study involved eleven patients (lung cancer, 8; gastric carcinoma, 1; esophageal carcinoma, 2). Approximately 150 MBq of [68Ga]Ga-NODAGA-SNA006 with varying nanobody masses (100 µg, 300 µg, 500 µg, 800 µg) was administered, and PET/computed tomography (CT) scans were performed at 15-30, 60-90 and 120 min postinjection (p.i.). Data regarding biodistribution, pharmacokinetics and radiation dosimetry were evaluated. CD8+ T-cell infiltration in biopsy samples was also measured via immunohistochemistry (IHC) for correlation analysis with the tumor uptake of [68Ga]Ga-NODAGA-SNA006 PET.[68Ga]Ga-NODAGA-SNA006 was well tolerated by all eleven subjects. The highest radioactive uptake was observed in the spleen, followed by the kidneys and bladder. Liver uptake decreased with increasing nanobody mass. Rapid clearance (t1/2