Voxel-based dosimetry of iron oxide nanoparticles based 177Lu-labeled folate conjugates targeted SPECT/CT imaging of mice

Abstract

Peptide-receptor radionuclide therapy (PRRT) has gained increasing importance for the treatment of various cancers including lymphoma, glioblastoma, neuroendocrine tumors and prostate cancer. The effectiveness of targeted radionuclide therapy (TRT) depends primarily on the absorbed dose rate and the total absorbed dose delivered to the tumor and to normal tissues. Hence, the absorbed dose must be determined as accurately as possible to obtain appropriate absorbed dose response–effect relationships. Due to the various limitations associated with organ-based dosimetry performed by MIRD schema, the voxel-based dosimetry has become essential for the assessment of more accurate absorbed dose. <br/> The folate receptor (FR) has been identified as a target associated with varieties of tumors including ovarian and cervical carcinoma. Therefore, several folic acid conjugates using diagnostic and therapeutic radionuclides have been developed for targeted imaging and therapy. However, the therapeutic concept with radiolabeled folate conjugates has not been applied yet for clinical application due to higher renal absorbed dose caused by increased uptake in kidneys. To overcome these challenges, we prepared iron oxide nanoparticle (IONPs) based radiolabeled folate conjugate (177Lu-IONPs-Folate) and performed voxel-based dosimetry using SPECT/CT imaging of normal mice. In this thesis, we first performed voxel-based dosimetry in normal mice from whole-body 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging to evaluate the feasibility and reliability of image-based preclinical dosimetry using GATE MC toolkit. Secondly, we evaluated system performance and quantitative accuracy of NanoSPECT/CT scanner for 177Lu radioisotope using point source and uniform phantom studies. Finally, we estimated the absorbed doses at voxel-level using GATE MC from the SPECT/CT images of normal mice performed with 177Lu-Folate, 177Lu-IONPs and 177Lu-IONPs-Folate. We also calculated organ-based absorbed dose in the given organs due to all three radiotracers using MIRD schema. <br/> MC simulation considers the true activity distribution and tissue heterogeneity during whole-body absorbed dose estimation at voxel-level. Therefore, the voxel-based absorbed dose estimated in the organs of mice from 18F-FDG PET would be more accurate. The results obtained from measured performance parameters were convincing to conduct preclinical SPECT/CT imaging. We found that the absorbed dose to the kidneys was significantly decreased when Iron-oxide nanoparticle based 177Lu-lableled folate conjugate (177Lu-IONPs-Folate) was used compared to 177Lu-Folate. <br/> In conclusion, the absorbed dose values in the organs obtained at voxel-level using individualized activity and media distributions would be more accurate. This method can be used for personalized dosimetry in TRT to estimate maximum tolerated activity for therapy planning.<br/>