Estimation of Human Absorbed Dose for a Novel 177Lu-Labeled Nanoplatform Based on Murine Biodistribution: A Comparative Study of Dosimetric Estimates Derived from ICRP 89 Reference Data and OLINDA/EXM S-Values

Multifunctional theranostic agents are increasingly needed for cancer management because they can integrate tumor diagnosis, image-guided therapy, and treatment monitoring within a single platform. However, many existing radiopharmaceuticals are limited by single-modality performance, suboptimal tumor retention, or incomplete preclinical dosimetric characterization. This study evaluates a theranostic nanoplatform (NPF), [177Lu]Lu@Gd-CdSe, with an ultra-small diameter of approximately 3.5 nm, for radionuclide-based cancer targeting and preclinical dosimetric assessment. The radiolabeled NPF achieved a radiochemical purity (RCP) exceeding 99%. Stability in phosphate-buffered saline (PBS, 4 °C) and human serum (37 °C) remained above 90% up to 48 h and above 82% at 168 h. In vivo biodistribution was evaluated in 4T1 tumor-bearing BALB/c mice (n=3 per time point) at 2, 4, 24, 48, and 164 h post-injection. The NPF showed favorable tumor accumulation, peaking at 13.27 %ID/g at 24 h. Tumor-to-muscle (T/M) and tumor-to-blood (T/B) ratios reached 196.99 and 196.97 at 164 h, respectively, indicating prolonged tumor retention and low background activity. Human organ absorbed doses were estimated from mouse biodistribution data using mass extrapolation within the medical internal radiation dose (MIRD) formalism, with calculations performed using OLINDA/EXM software and ICRP Publication 89 reference data. The average absorbed doses for the liver, kidneys, and spleen were 0.23, 0.13, and 0.13 mGy/MBq, respectively, identifying them as the main dose-limiting organs. Overall, [177Lu]Lu@Gd-CdSe demonstrated high RCP, acceptable in vitro stability, favorable tumor accumulation, prolonged tumor retention, and a measurable preclinical dosimetric profile. These findings support further preclinical investigation of this NPF as a potential theranostic agent.