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

TL;DR

This study shows that partial volume correction enhances the accuracy of tumor dosimetry in preclinical head and neck cancer models using theranostic 124I/131I-CLR1404, supporting personalized radiotherapy approaches.

Contribution

It introduces a novel partial volume correction method for 124I PET imaging that improves dosimetry accuracy in tumor models of head and neck cancer.

Findings

PVC increased uptake measurements by up to 188%.

Tumor dosimetry was significantly more accurate with PVC.

CLR 131 showed tumoricidal effects correlated with radiation dose.

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.