Background Accurate quantification of iodine uptake is essential for performing pre-treatment dosimetry of ¹³¹I therapy after redifferentiation of radioiodine-refractory thyroid cancer. Standardized procedures for ¹²⁴I PET/CT-based dosimetry are currently lacking. We aim to evaluate the relation between ¹⁸F and ¹²⁴I imaging for two different PET/CT scanners, the effect of bias correction on recovery across scanners and investigate the impact of clinically-encountered background (BG)-to-lesion ratios on recovery correction. Methods Cylindrical and NEMA body phantoms were scanned following vendor-recommended ¹²⁴I acquisition using clinically representative activity concentrations (5.6–5.7 kBq/mL in cylindrical phantom, 45.1–59.2 kBq/mL in NEMA spheres) and BG-to-sphere ratios (∼1:125 to 1:infinity) using two digital PET/CT scanners (Philips Vereos and GE Healthcare Omni). Additionally, BG-to-sphere ratio ∼1:10 was acquired to compare ¹²⁴I to the EARL ¹⁸F standards 1 (EARL1). Calibration accuracy and recovery coefficients (RC_max, RC_mean) were compared between scanners with and without bias correction. Results ¹²⁴I recovery was ∼20% higher for the Omni compared to the Vereos, showing calibration accuracies of 1.12–1.15 vs. 0.94, and RC_mean reaching 0.86 vs. 0.69. After bias correction, RC_mean was comparable between scanners ('1%) but below the lower limits of EARL1. A single fit for recovery correction (R² = 0.97) was obtained for different BG-to-sphere ratios for both scanners as RC_mean was comparable (p ' 0.4). Conclusion Vendor-recommended ¹²⁴I acquisition and reconstruction leads to differences in quantification but can be compensated using a bias correction. Recovery correction is minimally affected by different BG-to-lesion ratios, suggesting that one RC curve is sufficient, simplifying ¹²⁴I calibration procedures in studies requiring ¹²⁴I quantification.

Background: Prior studies show that short-term treatment using tyrosine kinase inhibitors (TKIs) can reinduce radioiodine uptake and warrant ¹³¹I therapy in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC). We aim to evaluate the potential of standard-of-care TKI lenvatinib to reinduce clinically meaningful radioiodine retention. Methods: Nine RAI-R DTC patients starting lenvatinib treatment for progressive advanced or metastatic disease, were included and underwent rhTSH-stimulated ¹²⁴I dosimetric procedures at baseline, week 6 (N=7) and week 12 (N=8). At all timepoints, the fraction of patients eligible for ¹³¹I therapy with a maximal activity of 7.4 GBq was assessed. Patients were considered eligible if at least one target lesion showed an expected mean absorbed dose ≥20 Gy. In total, 23 target lesions were segmented on¹²⁴I PET/CT images and their volumes estimated using low-dose CT images. Lesion size-specific recovery correction was applied to the measured mean activity concentration at each timepoint. Tumor dosimetry was performed using a mono-exponential fit and S-values from an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms (IDAC-Dose2.1). Mean absorbed lesion dose per administered activity (LDpA), 24h-uptake and residence time in target lesions were compared between time points. Results: By our definition, none of the patients were found eligible for ¹³¹I therapy at any timepoint. Lenvatinib-induced partial response was observed in 59% and 75% of target lesions at week 6 and 12, respectively. Median LDpA was 0.08 (IQR: 0.04-0.17), 0.18 (0.08-0.36) and 0.17 (0.09-0.37) Gy/GBq for week 0, 6 and 12, respectively (p=0.08). The 24h-uptake and residence time were comparable between timepoints (p>0.22). Conclusion: Redifferentiation of RAI-R DTC to reinduce radioiodine uptake to a level that warrants ¹³¹I therapy may not be established by short-term lenvatinib treatment. Multi-targeted TKIs may not be as potent as selective TKIs in reinducing clinically meaningful radioiodine retention.