Preparation and Dosimetry Assessment of 166Dy2O3/166Ho2O3-iPSMA Nanoparticles for Targeted Hepatocarcinoma Radiotherapy.

This research aimed to prepare 166Dy2O3-iPSMA/166Ho2O3-iPSMA nanoparticles (166Dy2O3/166Ho2O3-iPSMA NPs) and assess the radiation absorbed dose produced by the nanosystem to hepatic cancer cells by using experimental in vitro and in vivo biokinetic data. Dy2O3NPs were synthesized and functionalized with the prostate-specific membrane antigen inhibitor peptide (iPSMA). Fourier transform infrared (FTIR) spectroscopy, transmission electron microscope (TEM), dynamic light scattering (DSL) and zeta potential analyses indicated the formation of Dy2O3-iPSMA NPs (46.11 ± 13.24 nm). After neutron activation, a stable 166Dy2O3/166Ho2O3- iPSMA nanosystem was obtained, which showed adequate affinity to the PSMA receptor in HepG2 cancer cells (Kd = 9.87 ± 2.27 nM). in vitro studies indicated high 166Dy2O3/166Ho2O3-iPSMA internalization in cancer cells, with high radiation doses to cell nuclei (107 Gy) and cytotoxic effects, resulting in a significant reduction in HepG2 cell viability (decreasing to 2.12 ± 0.31%). After intratumoral administration in mice, the nanosystem biokinetic profile indicated significant retention into the tumoral mass, producing ablative radiation doses (>70 Gy).

Assessment of the radiation absorbed dose produced by 177Lu-iPSMA, 225Ac-iPSMA and 223RaCl2 to prostate cancer cell nuclei in a bone microenvironment model.

This research aimed to assess the radiation absorbed dose produced by 177Lu-iPSMA (177Lu-prostate specific membrane antigen inhibitor), 225Ac-iPSMA and 223RaCl2 to prostate cancer cell nuclei in a simplified model of bone by using an experimental in-vitro prostate cancer LNCaP cell biokinetic study and Monte Carlo simulation with the MCNPX code. Results showed that 225Ac-iPSMA releases a nine hundred-fold radiation dose greater than 177Lu-iPSMA and 14 times more than 223RaCl2 per unit of activity retained in bone. 225Ac-iPSMA could be the best option for treatment of bone metastases in prostate cancer.

Multimodal molecular 3D imaging for the tumoral volumetric distribution assessment of folate-based biosensors.

The aim of this study was to characterize the in vivo volumetric distribution of three folate-based biosensors by different imaging modalities (X-ray, fluorescence, Cerenkov luminescence, and radioisotopic imaging) through the development of a tridimensional image reconstruction algorithm. The preclinical and multimodal Xtreme imaging system, with a Multimodal Animal Rotation System (MARS), was used to acquire bidimensional images, which were processed to obtain the tridimensional reconstruction. Images of mice at different times (biosensor distribution) were simultaneously obtained from the four imaging modalities. The filtered back projection and inverse Radon transformation were used as main image-processing techniques. The algorithm developed in Matlab was able to calculate the volumetric profiles of 99mTc-Folate-Bombesin (radioisotopic image), 177Lu-Folate-Bombesin (Cerenkov image), and FolateRSense™ 680 (fluorescence image) in tumors and kidneys of mice, and no significant differences were detected in the volumetric quantifications among measurement techniques. The imaging tridimensional reconstruction algorithm can be easily extrapolated to different 2D acquisition-type images. This characteristic flexibility of the algorithm developed in this study is a remarkable advantage in comparison to similar reconstruction methods.

A new Monte Carlo code for light transport in biological tissue.

The aim of this work was to develop an event-by-event Monte Carlo code for light transport (called MCLTmx) to identify and quantify ballistic, diffuse, and absorbed photons, as well as their interaction coordinates inside the biological tissue. The mean free path length was computed between two interactions for scattering or absorption processes, and if necessary scatter angles were calculated, until the photon disappeared or went out of region of interest. A three-layer array (air-tissue-air) was used, forming a semi-infinite sandwich. The light source was placed at (0,0,0), emitting towards (0,0,1). The input data were: refractive indices, target thickness (0.02, 0.05, 0.1, 0.5, and 1 cm), number of particle histories, and λ from which the code calculated: anisotropy, scattering, and absorption coefficients. Validation presents differences less than 0.1% compared with that reported in the literature. The MCLTmx code discriminates between ballistic and diffuse photons, and inside of biological tissue, it calculates: specular reflection, diffuse reflection, ballistics transmission, diffuse transmission and absorption, and all parameters dependent on wavelength and thickness. The MCLTmx code can be useful for light transport inside any medium by changing the parameters that describe the new medium: anisotropy, dispersion and attenuation coefficients, and refractive indices for specific wavelength.