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

Su Bin Kim; Min Seob Lee; In Ho Song; Hyun Soo Park; Sang Eun Kim

doi:10.1021/acs.molpharmaceut.3c00073

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

Mol Pharm. 2023 Jul 3;20(7):3460-3470. doi: 10.1021/acs.molpharmaceut.3c00073. Epub 2023 Jun 9.

Authors

Su Bin Kim^{1

2}, Min Seob Lee², In Ho Song², Hyun Soo Park^{2

3}, Sang Eun Kim^{2

3

4

5}

Affiliations

¹ Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
² Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam 13620, Korea.
³ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
⁴ Advanced Institutes of Convergence Technology, 145 Gwanggyo-ro, Yeongtong-gu, Suwon 16229, Korea.
⁵ BIK Therapeutics Inc., 172 Dolma-ro, Bundang-gu, Seongnam 13605, Korea.

PMID: 37294909
DOI: 10.1021/acs.molpharmaceut.3c00073

Abstract

Precise dosimetry has gained interest for interpreting the response assessments of novel therapeutic radiopharmaceuticals, as well as for improving conventional radiotherapies such as the "one dose fits all" approach. Although radioiodine as same-element isotope theranostic pairs has been used for differentiated thyroid cancer (DTC), there are insufficient studies on the determination of its dosing regimen for personalized medicine and on extrapolating strategies for companion diagnostic radiopharmaceuticals. In this study, DTC xenograft mouse models were generated after validating iodine uptakes via sodium iodine symporter proteins (NIS) through in vitro assays, and theranostic surrogacy of companion radiopharmaceuticals was investigated in terms of single photon emission computed tomography (SPECT) imaging and voxel-level dosimetry. Following a Monte Carlo simulation, the hypothetical energy deposition/dose distribution images were produced as [¹²³I]NaI SPECT scans with the use of ¹³¹I ion source simulation, and dose rate curves were used to estimate absorbed dose. For the tumor, a peak concentration of 96.49 ± 11.66% ID/g occurred 2.91 ± 0.42 h after [¹²³I]NaI injection, and absorbed dose for ¹³¹I therapy was estimated as 0.0344 ± 0.0088 Gy/MBq. The absorbed dose in target/off-target tissues was estimated by considering subject-specific heterogeneous tissue compositions and activity distributions. Furthermore, a novel approach was proposed for simplifying voxel-level dosimetry and suggested for determining the minimal/optimal scan time points of surrogates for pretherapeutic dosimetry. When two scan time points were set to T_max and 26 h and the group mean half-lives were applied to the dose rate curves, the most accurate absorbed dose estimates were determined [-22.96, 2.21%]. This study provided an experimental basis to evaluate dose distribution and is expected hopefully to improve the challenging dosimetry process for clinical use.

Keywords: biodistribution; differentiated thyroid cancer; internal radiation dosimetry; simplified dosimetry; surrogate; theranostics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / drug therapy
Animals
Humans
Iodine Radioisotopes / therapeutic use
Mice
Precision Medicine
Radiometry / methods
Radiopharmaceuticals / therapeutic use
Thyroid Neoplasms* / diagnostic imaging
Thyroid Neoplasms* / drug therapy
Thyroid Neoplasms* / radiotherapy

Substances

Iodine-131
Iodine-123
Iodine Radioisotopes
Radiopharmaceuticals