Partial volume correction improves theranostic 124I/131I-CLR1404 tumor dosimetry in xenograft models of head and neck cancer

Abstract

Combination radiopharmaceutical and external beam radiotherapy offers the potential to diminish locoregional toxicity that remains dose-limiting in the conventional treatment paradigm for recurrent head and neck cancer (HNC). In this study, we investigated the tumor targeting capacity of 131I-CLR1404 (CLR 131) in various HNC xenograft mouse models and the impact of partial volume correction on theranostic dosimetry based on 124I-CLR1404 (CLR 124) PET/CT imaging. Methods: Mice bearing flank tumor xenograft models of HNC (6 murine cell line- and 6 human patient-derived) were intravenously administered 6.5-9.1 MBq of CLR 124 and imaged five times over the course of six days using microPET/CT. In vivo tumor uptake of CLR 124 was assessed and partial volume corrections (PVC) for 124I were applied using a novel preclinical phantom. Using subject-specific theranostic dosimetry estimations for CLR 131 based on CLR 124 imaging, a discrete radiation dose escalation study was performed to evaluate tumor growth response to CLR 131 relative to a single fraction of XRT. Results: PET imaging demonstrated consistent tumor selective uptake and retention of CLR 124 across all HNC xenograft models. Peak uptake of 4.4 +/- 0.8% and 4.2 +/- 0.4% was observed in SCC-22B and UW-13, respectively. PVC application increased uptake measures by 47-188% and reduced absolute differences between in vivo and ex vivo uptake measurements from 3.3 to 1.0 %IA/g. Tumor dosimetry averaged over all HNC models was 0.85 +/- 0.27 Gy/MBq (1.58 +/- 0.46 Gy/MBq with PVC). Therapeutic CLR 131 studies demonstrated a variable, but linear relationship between CLR 131 radiation dose and tumor growth delay (p < 0.05). Conclusion: CLR 131 demonstrated tumoricidal capacity in preclinical HNC tumor models and the theranostic pairing of CLR 124/131 presents a promising new treatment approach for personalizing administration of CLR 131.