The use of single-timepoint images to link administered radioiodine activity (MBq) to a prescribed lesion radiation-absorbed dose (cGy): a regression-based prediction interval tool for the management of well-differentiated thyroid cancer patients

PurposeTo introduce a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine I-131 therapy (RAI) for metastatic differentiated thyroid cancer (mDTC) based on single-timepoint imaging of individual lesion uptake by I-124 PET.MethodsPatients referred for RAI therapy of mDTC were enrolled in institutionally approved protocols. A total of 208 mDTC lesions (in 21 patients) with SUVmax > 1 underwent quantitative PET scans at 24, 48, 72, and 120 h post-administration of 222 MBq of theranostic NaI-I-124 to determine the individual lesion radiation-absorbed dose. Using a general estimating equation, a prediction curve for biomarker development was generated in the form of a best-fit regression line and 95% prediction interval, correlating individual predicted lesion radiation dose metrics, with candidate biomarkers (predictors) such as SUVmax and activity in microcurie per gram, from a single imaging timepoint.ResultsIn the 169 lesions (in 15 patients) that received I-131 therapy, individual lesion cGy varied over 3 logs with a median of 22,000 cGy, confirming wide heterogeneity of lesion radiation dose. Initial findings from the prediction curve on all 208 lesions confirmed that a 48-h SUVmax was the best predictor of lesion radiation dose and permitted calculation of the I-131 activity required to achieve a lesional threshold radiation dose (2000 cGy) within defined confidence intervals.ConclusionsBased on MIRD lesion-absorbed dose estimates and regression statistics, we report on the feasibility of a new single-timepoint I-124-PET-based dosimetry biomarker for RAI in patients with mDTC. The approach provides clinicians with a tool to select personalized (precision) therapeutic administration of radioactivity (MBq) to achieve a desired target lesion-absorbed dose (cGy) for selected index lesions based on a single 48-h measurement I-124-PET image, provided the selected activity does not exceed the maximum tolerated activity (MTA) of < 2 Gy to blood, as is standard of care at Memorial Sloan Kettering Cancer Center.

Automated summary

This article introduces a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine I-131 therapy (RAI) for metastatic differentiated thyroid cancer (mDTC) based on single-timepoint imaging of individual lesion uptake by I-124 PET.