RT Journal Article SR Electronic T1 CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 720 OP 726 DO 10.2967/jnumed.121.262485 VO 63 IS 5 A1 Michael D. Farwell A1 Raymond F. Gamache A1 Hasan Babazada A1 Matthew D. Hellmann A1 James J. Harding A1 Ron Korn A1 Alessandro Mascioni A1 William Le A1 Ian Wilson A1 Michael S. Gordon A1 Anna M. Wu A1 Gary A. Ulaner A1 Jedd D. Wolchok A1 Michael A. Postow A1 Neeta Pandit-Taskar YR 2022 UL http://jnm.snmjournals.org/content/63/5/720.abstract AB There is a need for in vivo diagnostic imaging probes that can noninvasively measure tumor-infiltrating CD8+ leukocytes. Such imaging probes could be used to predict early response to cancer immunotherapy, help select effective single or combination immunotherapies, and facilitate the development of new immunotherapies or immunotherapy combinations. This study was designed to optimize conditions for performing CD8 PET imaging with 89Zr-Df-IAB22M2C and determine whether CD8 PET imaging could provide a safe and effective noninvasive method of visualizing the whole-body biodistribution of CD8+ leukocytes. Methods: We conducted a phase 1 first-in-humans PET imaging study using an anti-CD8 radiolabeled minibody, 89Zr-Df-IAB22M2C, to detect whole-body and tumor CD8+ leukocyte distribution in patients with metastatic solid tumors. Patients received 111 MBq of 89Zr-Df-IAB22M2C followed by serial PET scanning over 5–7 d. A 2-stage design included a dose-escalation phase and a dose-expansion phase. Biodistribution, radiation dosimetry, and semiquantitative evaluation of 89Zr-Df-IAB22M2C uptake were performed in all patients. Results: Fifteen subjects with metastatic melanoma, non–small cell lung cancer, and hepatocellular carcinoma were enrolled. No drug-related adverse events or abnormal laboratory results were noted except for a transient increase in antidrug antibodies in 1 subject. 89Zr-Df-IAB22M2C accumulated in tumors and CD8-rich tissues (e.g., spleen, bone marrow, nodes), with maximum uptake at 24–48 h after injection and low background activity in CD8-poor tissues (e.g., muscle and lung). Radiotracer uptake in tumors was noted in 10 of 15 subjects, including 7 of 8 subjects on immunotherapy, 1 of 2 subjects on targeted therapy, and 2 of 5 treatment-naïve subjects. In 3 patients with advanced melanoma or hepatocellular carcinoma on immunotherapy, posttreatment CD8 PET/CT scans demonstrated increased 89Zr-Df-IAB22M2C uptake in tumor lesions, which correlated with response. Conclusion: CD8 PET imaging with 89Zr-Df-IAB22M2C is safe and has the potential to visualize the whole-body biodistribution of CD8+ leukocytes in tumors and reference tissues, and may predict early response to immunotherapy.