Dataset Information

Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry.

ABSTRACT: Background: Delivery of radiotherapeutic dose to recurrent head and neck cancer (HNC) is primarily limited by locoregional toxicity in conventional radiotherapy. As such, HNC patients stand to benefit from the conformal targeting of primary and remnant disease achievable with radiopharmaceutical therapies. In this study, the authors investigated the tumor targeting capacity of ¹³¹I-CLR1404 (iopofosine I-131) in various HNC xenograft mouse models and the impact of partial volume correction (PVC) on theranostic dosimetry based on ¹²⁴I-CLR1404 (CLR 124) positron emission tomography (PET)/computed tomography (CT) imaging. Methods: Mice bearing flank tumor xenograft models of HNC (six murine cell line and six human patient derived) were intravenously administered 6.5-9.1 MBq of CLR 124 and imaged five times over the course of 6 d using microPET/CT. In vivo tumor uptake of CLR 124 was assessed and PVC for ¹²⁴I was applied using a novel preclinical phantom. Using subject-specific theranostic dosimetry estimations for iopofosine I-131 based on CLR 124 imaging, a discrete radiation dose escalation study (2, 4, 6, and 8 Gy) was performed to evaluate tumor growth response to iopofosine I-131 relative to a single fraction of external beam radiation therapy (6 Gy). 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 squamous cell carcinoma-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 percent injected activity per gram. Tumor dosimetry averaged over all HNC models was 0.85 ± 0.27 Gy/MBq (1.58 ± 0.46 Gy/MBq with PVC). Therapeutic iopofosine I-131 studies demonstrated a variable, but linear relationship between iopofosine I-131 radiation dose and tumor growth delay (p < 0.05). Conclusions: Iopofosine I-131 demonstrated tumoricidal capacity in preclinical HNC tumor models and the theranostic pairing with CLR 124 presents a promising new treatment approach for personalizing administration of iopofosine I-131.

SUBMITTER: Marsh IR

PROVIDER: S-EPMC10516227 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry.

Marsh Ian R IR Li Chunrong C Grudzinski Joseph J Jeffery Justin J Longhurst Colin C Adam David P DP Hernandez Reinier R Weichert Jamey P JP Harari Paul M PM Bednarz Bryan P BP

Cancer biotherapy & radiopharmaceuticals 20230405 7

Background: Delivery of radiotherapeutic dose to recurrent head and neck cancer (HNC) is primarily limited by locoregional toxicity in conventional radiotherapy. As such, HNC patients stand to benefit from the conformal targeting of primary and remnant disease achievable with radiopharmaceutical therapies. In this study, the authors investigated the tumor targeting capacity of 131I-CLR1404 (iopofosine I-131) in various HNC xenograft mouse models and the impact of partial ...[more]

PMID: 37022739

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Project description:BackgroundWe present a method for extracting arterial input functions from dynamic [18F]FLT PET images of the head and neck, directly accounting for the partial volume effect. The method uses two blood samples, for which the optimum collection times are assessed.MethodsSix datasets comprising dynamic PET images, co-registered computed tomography (CT) scans and blood-sampled input functions were collected from four patients with head and neck tumours. In each PET image set, a region was identified that comprised the carotid artery (outlined on CT images) and surrounding tissue within the voxels containing the artery. The time course of activity in the region was modelled as the sum of the blood-sampled input function and a compartmental model of tracer uptake in the surrounding tissue.The time course of arterial activity was described by a mathematical function with seven parameters. The parameters of the function and the compartmental model were simultaneously estimated, aiming to achieve the best match between the modelled and imaged time course of regional activity and the best match of the estimated blood activity to between 0 and 3 samples. The normalised root-mean-square (RMSnorm) differences and errors in areas under the curves (AUCs) between the measured and estimated input functions were assessed.ResultsA one-compartment model of tracer movement to and from the artery best described uptake in the tissue surrounding the artery, so the final model of the input function and tissue kinetics has nine parameters to be estimated. The estimated and blood-sampled input functions agreed well when two blood samples, obtained at times between 2 and 8 min and between 8 and 60 min, were used in the estimation process (RMSnorm values of 1.1 ± 0.5 and AUC errors for the peak and tail region of the curves of 15% ± 9% and 10% ± 8%, respectively). A third blood sample did not significantly improve the accuracy of the estimated input functions.ConclusionsInput functions for FLT-PET studies of the head and neck can be estimated well using a one-compartment model of tracer movement and TWO blood samples obtained after the peak in arterial activity.

Dataset Information

Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry.

Publications

Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry.

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