JMIR Publications

ABSTRACT

Background:

Targeted radiopharmaceutical therapy (TRT) offers a promising approach for cancer treatment by delivering radiation directly to tumor cells while sparing healthy tissues. Accurate dosimetry of organs and tumors is crucial to optimize therapeutic efficacy and minimize toxicity, especially for dose-limiting organs like the kidneys. Although routine dosimetry using single-photon emission computed tomography (SPECT) is recommended by guidelines, its widespread clinical application remains limited. This is due to a lack of consensus on the optimal frequency and timing of SPECT scans for accurate dosimetry, which leads to variability in clinical practice and hinders robust dose-response relationships. Furthermore, discrepancies in dose estimates among different simulation software programs pose a significant challenge to standardizing dosimetry workflows. Therefore, this study aims to identify the optimal SPECT imaging schedule, evaluate differences among simulation software programs, and establish a standardized protocol for future epidemiological research to determine the definition of organ tolerance doses and facilitate wider adoption of personalized TRT regimens.

Methods:

This exploratory observational trial will determine the optimal SPECT imaging protocol and consistency of dosimetry estimates using software programs for Lutetium-177 (Lu-177)-DOTATATE therapy in patients with neuroendocrine tumor. In a single treatment cycle, SPECT imaging will be performed at 4h, 24h, 96h, and 168h following Lu-177-DOTATATE administration. For each patient, absorbed doses calculated from all time-points (4-point method) will be the reference standard, compared with estimates from 1- to 3-point methods. Fifteen dose simulations will be conducted per patient. The primary endpoint is the calculated kidney dose, with secondary analyses including tumor and other organ dosimetry. Cross-comparisons will assess software program differences. A dose deviation of <5–10% will be considered acceptable. Ethics approval was obtained from the Tokushukai Group Ethics Committee (Approval No. 2447; UMIN000057478). This study addresses the need for a standardized dosimetry workflow for Lu-177-DOTATATE therapy, given the absence of prospective dosimetry trials in Japan and variability in kidney dose estimates across centers. Discussion: This study will evaluate whether simplified SPECT imaging protocols can maintain dosimetric accuracy while reducing the burden on patients and providers. It will also compare absorbed dose estimates across software programs to assess consistency and reliability. Findings will be disseminated through open-access peer-reviewed journals and relevant conferences and events.