First in Human Phase I Imaging Study With 89Zr-IAB22M2C Anti CD8 Minibody in Patients with Solid Tumors

Objectives: Immune modulating agents are becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients respond to immunotherapy. Tumor infiltrating CD 8 positive T lymphocytes play a central role in the anti-tumor immune response. Non Invasive imaging of CD8 T cells can provide new insights in the mechanisms of immunotherapy and potentially predict treatment responses. We are therefore studying the safety and feasibility of PET/CT imaging with a radiolabeled minibody (Mb) against CD8 (89Zr-Df-IAB22M2C) for imaging CD8 positive T cells in patients undergoing immunotherapy.Methods : In an ongoing prospective study 2 pts (1 melanoma, 1 hepatocellular carcinoma) received 3 mCi of 89Zr-Df-IAB22M2C of radiolabeled Mb (0.2 and 0.5mg of Mb) followed by PET/CT scans at ~1-2 h, 6-8 24, 48 h and 120-144 h post injection(PI) . Serum samples and whole body (WB) counts were obtained at each imaging time point. All patients were monitored for vitals and side effects during and after the infusion up to the last time point of imaging. Biodistribution and uptake in normal organs, lymph nodes and tumor lesions was evaluated.Results: 89Zr-Df-IAB22M2C infusion was tolerated well and no immediate or delayed side effects were seen in either pt after injection. Activity in the serum cleared exceptionally rapidly for an antibody fragment, reaching an average of 5.7 %ID/l at 30 min post-injection and generally conformed to a bi-exponential function with respective partition coefficients; Tbiol of 10%ID/l; 0.9h and 1.5%ID/l; 152h. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h pi reaching peak levels by 24- 48 h pi. Maximum nodal uptake ranged from 4.0- 34.9 at 48 h pi. Spleen, bone marrow and liver also showed tracer uptake with SUVMAX of 115, 18.1 and 6.1, respectively. Renal uptake was relatively low and primarily in cortex with SUVmax of 7.2 at 24-48 h. Uptake in tumor lesions was seen in both patients, as early as 2 h imaging. The majority of lesions were seen by 24 h and maximum uptake in lesions was seen at 48 h in most sites Maximum lesion uptake, evaluated in 6 target lesions including 1 lesion in muscle, two liver lesions and 3 nodes ranged between 5.85- 22.8. While physiologic uptake was seen in liver in both patients, the HCC showed prominent uptake and was visualized with high contrast on PET/CT imaging (Figure). Conclusions: Preliminary data from this ongoing study shows that 89Zr-Df-IAB22M2C imaging is safe,