Theranostic Surrogacy of [123I]NaI for Differentiated Thyroid Cancer Radionuclide Therapy

Precise dosimetry has gained interest for interpretingthe responseassessments of novel therapeutic radiopharmaceuticals, as well asfor improving conventional radiotherapies such as the onedose fits all approach. Although radioiodine as same-elementisotope theranostic pairs has been used for differentiated thyroidcancer (DTC), there are insufficient studies on the determinationof its dosing regimen for personalized medicine and on extrapolatingstrategies for companion diagnostic radiopharmaceuticals. In thisstudy, DTC xenograft mouse models were generated after validatingiodine uptakes via sodium iodine symporter proteins(NIS) through in vitro assays, and theranostic surrogacyof companion radiopharmaceuticals was investigated in terms of singlephoton emission computed tomography (SPECT) imaging and voxel-leveldosimetry. Following a Monte Carlo simulation, the hypothetical energydeposition/dose distribution images were produced as [I-123]NaI SPECT scans with the use of I-131 ion source simulation,and dose rate curves were used to estimate absorbed dose. For thetumor, a peak concentration of 96.49 +/- 11.66% ID/g occurred 2.91 +/- 0.42 h after [I-123]NaI injection, and absorbed dosefor I-131 therapy was estimated as 0.0344 +/- 0.0088Gy/MBq. The absorbed dose in target/off-target tissues was estimatedby considering subject-specific heterogeneous tissue compositionsand activity distributions. Furthermore, a novel approach was proposedfor simplifying voxel-level dosimetry and suggested for determiningthe minimal/optimal scan time points of surrogates for pretherapeuticdosimetry. When two scan time points were set to T (max) and 26 h and the group mean half-lives were appliedto the dose rate curves, the most accurate absorbed dose estimateswere determined [-22.96, 2.21%]. This study provided an experimentalbasis to evaluate dose distribution and is expected hopefully to improvethe challenging dosimetry process for clinical use.

Automated summary

This study validated iodine uptakes and investigated theranostic surrogacy using DTC xenograft mouse models and SPECT imaging. Dosimetry was determined by simulating energy deposition/dose distribution and estimating absorbed dose. The study is expected to improve the challenging dosimetry process in clinical use.