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

Abstract

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

Methods: Patients referred for RAI therapy of mDTC were enrolled in institutionally approved protocols. A total of 208 mDTC lesions (in 21 patients) with SUV_max > 1 underwent quantitative PET scans at 24, 48, 72, and 120 h post-administration of 222 MBq of theranostic NaI-¹²⁴I 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 SUV_max and activity in microcurie per gram, from a single imaging timepoint.

Results: In the 169 lesions (in 15 patients) that received ¹³¹I 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 SUV_max was the best predictor of lesion radiation dose and permitted calculation of the ¹³¹I activity required to achieve a lesional threshold radiation dose (2000 cGy) within defined confidence intervals.

Conclusions: Based on MIRD lesion-absorbed dose estimates and regression statistics, we report on the feasibility of a new single-timepoint ¹²⁴I-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 ¹²⁴I-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.

Trial registration: NCT04462471, Registered July 8, 2020. NCT03647358, Registered Aug 27, 2018.

Keywords: Differentiated thyroid cancer; Dosimetry; Iodine-124; PET/CT; Radioactive iodine therapy.

Fig. 1

Example of four ¹²⁴I PET scans conducted at 24, 48, 72, and 120 h post-oral radioiodine administration. The clearance curves (SUV_max plotted vs. time in days) for individual neck and lung lesions of size > 0.5 cc) are shown in the view graph. This patient has lung lesions exhibiting high radioiodine uptake and rapid clearance accompanied by neck nodes with low uptake and slow clearance. This is an example of a patient who was not selected for treatment, since overall dose for several lesions was well below the 2000-cGy threshold

Fig. 2

Prediction curve for the best predictor as the ¹²⁴I PET imaging biomarker. ln-48-h SUV_max (optimal predictor) vs. ln-AUC (each color represents a patient; each dot is a lesion; the black line is the average linear regression line from the general estimating equation estimate while the gray area is the 95% prediction interval, which encompasses 95% of all lesions AUC at a particular 48-h SUV_max, from the lowest value at the 2.5 percentile to the highest value at the 97.5 percentile). Because a logarithmic transformation is used, the distance between the average prediction and the measured values can be larger than they appeared

Fig. 3

Results of leave-one-out cross-validation (SUV_max analysis). For each patient (separate quadrant), the AUC as predicted by our model is represented by a blue point while the blue line represents the 95% PI. The orange dots represent the actual AUC as measured on the lesion

Fig. 5

Distribution of radioactive iodine treatment dose given in 169 treated lesions (15 patients)

Fig. 4

Maximum-intensity projection (MIP) PET ¹²⁴I images at 48 h of 21 patents in the teaching set