Abstract LB058: Imaging of CD8+ cytotoxic T-cells by Zr-89-Df-IAB22M2C PET/MRI: First clinical experience in patients with metastatic cancer
Authors: Schwenck Johannes , Sonanini Dominik , Ehrlichmann Walter , Kienzle Gabriele , Reischl Gerald , Krezer Pascal , Wilson Ian , Korn Ron , Gonzalez-Menendez Irene , Quintanilla-Martinez Leticia , Seith Ferdinand , Forschner Andrea , Eigentler Thomas , Zender Lars , Röcken Martin , Pichler Bernd , Flatz Lukas , Kneilling Manfred , la Fougere Christian 
Published: June 2022

Abstract
CD8+ cytotoxic T cells are key players in anti-cancer immune responses as they destroy MHC class I-dependent tumor cells. Therefore, the spatial distribution of CD8+ cytotoxic T cells might represent an important surrogate for the response to cancer immunotherapy including immune checkpoint inhibitor therapy ICT. The radiolabeled minibody [89Zr]Zr-Df-IAB22M2C is characterized by a high affinity to human CD8 and was already investigated in a phase I study. Here, we present our first experience with the non invasive in vivo assessment of the whole body CD8 T cell distribution in cancer patients using clinical [89Zr]Zr-Df-IAB22M2C PET/MRI. In total 8 patients with metastasized cancers (5 x malignant melanoma; 1 x choroidal melanoma, 1 x NSCLC and 1 x sarcoma) were studied before (n = 3) or during (n = 5) ICT. Multiparametric PET/MRI was performed 24 h after injection of 74.2±17.9 MBq [89Zr]Zr-Df-IAB22M2C (1.1 - 1.8 mg Df-IAB22M2C) on a Siemens Biograph mMR System (SiemensHealthineers, Erlangen, Germany). The whole body distribution of the [89Zr]Zr-Df-IAB22M2C tracer was analyzed with a special focus on tumors/metastases as well as primary and secondary lymphatic organs. The PET tracer [89Zr]Zr-Df-IAB22M2C was well tolerated without any reported side effects. The PET/MRI acquisitions 24h p.i. of [89Zr]Zr-Df-IAB22M2C revealed a comparably low background signal with only a minor blood pool and unspecific tissue retention. Regarding the primary and secondary lymphoid organs we observed a high interpatient variability of the tracer uptake. Four out of five patients with previous ICT exhibited a relatively high [89Zr]Zr-Df-IAB22M2C uptake in the bone marrow. Also a large number of non metastatic lymph nodes yielded a pronounced [89Zr]Zr-Df-IAB22M2C uptake in four patients. Strikingly, a low [89Zr]Zr-Df-IAB22M2C uptake in the spleen compared to the liver (liver/spleen ratio &lt; 10) was observed in 4 out of the 5 patients with cancer progression during ICT. Interestingly, only one metastasis with an intense tracer was detected in this patient cohort. This first clinical experiences revealed the feasibility to assess potential immune-related changes by [89Zr]Zr-Df-IAB22M2C PET/MRI. Considering these results we hypothesize that the whole body distribution of CD8+ cytotoxic T-cells assessed by non-invasive in vivo [89Zr]Zr-Df-IAB22M2C PET/MRI might be associated with the response to cancer immunotherapy which needs to be investigated in subsequent prospective trials.
Citation Format: Johannes Schwenck, Dominik Sonanini, Walter Ehrlichmann, Gabriele Kienzle, Gerald Reischl, Pascal Krezer, Ian Wilson, Ron Korn, Irene Gonzalez-Menendez, Leticia Quintanilla-Martinez, Ferdinand Seith, Andrea Forschner, Thomas Eigentler, Lars Zender, Martin Röcken, Bernd Pichler, Lukas Flatz, Manfred Kneilling, Christian la Fougere. Imaging of CD8+ cytotoxic T-cells by Zr-89-Df-IAB22M2C PET/MRI: First clinical experience in patients with metastatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB058.