First Clinical Experience With [89Zr]Zr-Df-IAB22M2C PET/MRI in Patients With Metastatic Cancer

Abstract Aim/Introduction: Despite the spectacular success of immune checkpoint inhibitor therapy (ICT) in patients with metastatic cancer, only a limited proportion of patients benefit from ICT. An important gatekeeper for the therapeutic response to ICT are CD8+ cytotoxic T cells which are able to recognize MHC class I-dependent tumor antigens and destroy tumor cells. The radiolabeled minibody [89Zr]Zr-Df-IAB22M2C has a high affinity for human CD8+ T cells and was already successfully tested in a phase I study. Here, we aimed to gain first clinical PET/MRI experience with the non-invasive assessment of the CD8+ T cell distribution in cancer patients by in vivo [89Zr]Zr-Df-IAB22M2C.Material and Methods: We investigated 8 patients with metastasized cancers undergoing ICT. Radiolabeling of Df-IAB22M2C with Zr-89 was performed according to Good Manufacturing Practice. Multiparametric PET/MRI was acquired 24 h after injection of 74.2±17.9 MBq [89Zr]Zr-Df-IAB22M2C. We analyzed the [89Zr]Zr-Df-IAB22M2C uptake within the metastases and primary and secondary lymphatic organs. Results: [89Zr]Zr-Df-IAB22M2C injection was tolerated well without noticeable side effects. The CD8 PET/MRI data acquisitions 24 hours post administration of [89Zr]Zr-Df-IAB22M2C revealed a good image quality with a relatively low background signal due to only low unspecific tissue uptake and marginal blood pool retention. Only two metastatic lesions showed a markedly increased tracer uptake in our cohort of patients. Furthermore, we observed a high interpatient variability in the [89Zr]Zr-Df-IAB22M2C uptake within the primary and secondary lymphoid organs. Four out of five ICT patients exhibited a rather high [89Zr]Zr-Df-IAB22M2C uptake in the bone marrow. Two of these four patients as well as two other patients yielded a pronounced [89Zr]Zr-Df-IAB22M2C uptake within non metastatic lymph nodes. Interestingly, cancer progression in ICT patients was associated with a relatively low [89Zr]Zr-Df-IAB22M2C uptake in the spleen compared to the liver in 4 out of the 6 patients. Conclusion: Our first clinical experiences revealed the feasibility of [89Zr]Zr-Df-IAB22M2C PET/MRI to assess potential immune-related changes in the metastases and the primary and secondary lymphatic organs. According to our results, we hypothesize that alteration in the [89Zr]Zr-Df-IAB22M2C uptake in primary and secondary lymphoid organs might be associated with the response to ICT.