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Objective: The aim of this pilot study was to explore intrapatient mixed metabolic response and early 18F-FDG PET response evaluation using predefined quantification strategies in patients with advanced KRAS wild-type colorectal adenocarcinoma (mCRC) treated with cetuximab. Methods: A 18F-FDG PET was performed at baseline and after 2 cycles of cetuximab. Metabolic response was categorized using thresholds suggested in PERCIST. Quantitative analysis was done for the sum of all target lesions, ≤ 5 lesions and the metabolically most active lesion per PET. Quantitative data were correlated with clinical benefit, according to RECIST v1.1, after two months of treatment. Results: In nine evaluable patients the total number of target lesions was 34 (1–8 per patient). Mixed metabolic response was observed in three out of seven patients with multiple target lesions, using TLG. Dichotomised metabolic data of the sum of all or ≤ 5 lesions had a concordance with clinical benefit of 89% using SULmax or SULpeak, and 100% using TLG. Evaluating the metabolically most active lesion, concordance was 89% for all three units. Additionally, the decrease in TLG was significantly correlated with PFS for all three quantification strategies. Conclusion: Mixed metabolic response was observed in nearly half of the patients with advanced KRAS wild-type mCRC treated with cetuximab. If ≤ 5 target lesions were evaluated using TLG clinical benefit was predicted correctly for all patients. Moreover, decrease in TLG is significantly correlated with the duration of PFS. Validation of these promising preliminary results in a larger cohort is currently on-going. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Cergutuzumab amunaleukin (CEA-IL2v) is an immunocytokine directed against carcinoembryonic antigen (CEA) containing an IL2v-moiety with abolished IL-2 receptor (IL-2R) α binding. We describe the biodistribution and tumor accumulation of 89 Zr-labeled CEA-IL2v. Twenty-four patients with advanced solid CEA positive (CEA+) or negative (CEA-) tumors received CEA-IL2v 6 mg (4 CEA+; 3 CEA-), 20 mg (9 CEA+), or 30 mg (4 CEA+; 4 CEA-) biweekly. In cycle 1, 2 mg of the total dose comprised 89 Zr-CEA-IL2v (50 MBq) and serial 89 Zr-PET imaging was conducted. Four CEA+ patients with visually confirmed 89 Zr-CEA-IL2v tumor accumulation at 20 mg had repeated 89 Zr-PET imaging during cycle 4. 89 Zr-CEA-IL2v immuno-PET demonstrated preferential drug accumulation in CEA+ tumors (%ID/mL peak CEA- 3.6 × 10 -3 vs. CEA+ 6.7 ×∙10 -3 ). There was a non-significant trend towards dose-dependent tumor uptake, with higher uptake at doses ≥20 mg. Biodistribution was dose- and CEA-independent with major accumulation in lymphoid tissue compatible with IL-2R binding. Reduced exposure and reduced tumor accumulation (%ID/mL peak 57% lower) on cycle 4 vs. cycle 1 was consistent with peripheral expansion of immune cells. The findings of this immune PET imaging study with 89 Zr-CEA-IL2v support the therapeutic concept of CEA-IL2v, confirming selective and targeted tumor accumulation with this novel immunocytokine., Competing Interests: CONFLICTS OF INTEREST T.N. is a former employee of Roche; J.J.L.T. and J.S. are employees of Roche; S.E. is an employee and shareholder of Roche; the other authors have nothing to disclose.