Personalized dosimetry of internal exposure to foci and organs at risk of patients: development and implementation of a methodological basis for dosimetric support of clinical trials of therapeutic radiopharmaceuticals

Abstract

The cluster of calculational and instrumental methods for estimation of personalized internal radiation doses to foci and organs at risk among patients undergoing to therapy by radiopharmaceuticals has been developed. The developed set of methods was used for dosimetrical support of clinical trials of therapeutic radiopharmaceuticals: a) Lu-177-DOTA-PSMA (or "Lutaprost") targeted for radioligand therapy of metastatic castrate-resistant prostate cancer; b) Re-188 albumin microspheres 5-10 μm (or "Artroren") targeted for radiosynovectomy in the local treatment of chronic inflammatory diseases of the joints and c) 188Re albumin microspheres 20-40 μm (or "Gepatoren") targeted for intra-arterial radionuclide embolization in the treatment of inoperable liver cancer. The results of estimations absolute activities of radiopharmaceuticals and their dynamics during SPECT/CT scanning of radiopharmaceuticals in the body of patients were verified by measurements using physical phantoms of humans with different body weights and various standard activities of radionuclides distributed inside the phantoms. The developed cluster of programs (for calculating the absorbed fraction of energy in biostructures), relevant databases and instrumental methods were used as the basis for estimations personalized internal radiation doses in foci and organs at risk among patients included in clinical trials of the studied radiopharmaceuticals. Individual internal radiation doses in foci among 39 patients, included in the first phase of clinical trials of the three studied radiopharmaceuticals, were estimated. The analysis of the distribution of estimated doses shows that absorbed doses in foci are very differing not only in different patients, but also in different foci in the same patient. Irradiation doses in foci increase with an increasing in the administered activities of radiopharmaceuticals and, depending on the volume of foci, are within the following ranges: 1) in a case of “Lutaprost” – from 1.4 to 32 Gy (planned administered activity – 5 GBq), from 5.1 to 59 Gy (planned activity – 7.5 GBq), from 13 to 94 Gy (planned activity – 10 GBq); 2) in a case of "Arthroren" – from 17.5 to 74 Gy (planned administered activities – from 0.37 to 0.925 GBq); 3) in a case of “Gepatoren” – from 10.7 to 43 Gy (planned administered activities – from 1 to 3 GBq). Individual absorbed doses in organs at risk were estimated as well. Dose values in organs at risk also vary greatly between different patients and between different critical organs. These doses ranged from 0.01 to 7.4 Gy (39 patients), which is many times less than “commonly applied dose constraints” in radiotherapy.