Eugenio Torres-García

Multifunctional targeted therapy system based on 99mTc/177Lu-labeled gold nanoparticles-Tat(49–57)-Lys3-bombesin internalized in nuclei of prostate cancer cells

Radiolabeled gold nanoparticles may function simultaneously as radiotherapy and thermal ablation systems. The gastrin-releasing peptide receptor (GRP-r) is overexpressed in prostate cancer, and Lys(3) -bombesin is a peptide that binds with high affinity to the GRP-r. HIV Tat(49-57) is a cell-penetrating peptide that reaches the DNA. In cancer cells, (177) Lu shows efficient crossfire effect, whereas (99m) Tc that is internalized in the cancer cell nuclei acts as an effective system of targeted radiotherapy because of the biological Auger effect. The aim of this research was to evaluate the in vitro potential of (99m) Tc-labeled and (177) Lu-labeled gold nanoparticles conjugated to Tat(49-57)-Lys(3) -bombesin peptides ((99m) Tc/(177) Lu-AuNP-Tat-BN) as a plasmonic photothermal therapy and targeted radiotherapy system in PC3 prostate cancer cells. Peptides were conjugated to AuNPs (5 nm) by spontaneous reaction with the thiol group of cysteine (Cys). The effect on PC3 cell viability after laser heating of the AuNP-Tat-BN incubated with the cancer cells was conducted using an Nd:YAG laser pulsed for 5 ns at 532 nm (0.65 W/cm(2) ). For the (99m) Tc/(177) Lu-AuNP-Tat-BN to be obtained, the (177) Lu-DOTA-Gly-Gly-Cys and (99m) Tc-HYNIC-octreotide radiopeptides were first prepared and added simultaneously to a solution of AuNP-Tat-BN. (99m) Tc/(177) Lu-AuNP-Tat-BN (20 Bq/cell) was incubated with PC3 cells, and the effect on the cell proliferation was evaluated after 3 days. Fluorescence images of (99m) Tc/(177) Lu-AuNP-Tat-BN internalized in nuclei of PC3 were also obtained. After laser irradiation, the presence of AuNP-Tat-BN caused a significant increase in the temperature of the medium (46.4 vs 39.5 °C of that without AuNP) resulting in a significant decrease in PC3 cell viability down to 1.3%. After treatment with (99m) Tc/(177) Lu-AuNP-Tat-BN, the PC3 cell proliferation was inhibited. The nanosystem exhibited properties suitable for plasmonic photothermal therapy and targeted radiotherapy in the treatment of prostate cancer.

Dose per unit cumulated activity (S-values) for e− and beta emitting radionuclides in cancer cell models calculated by Monte Carlo simulation

Cell dosimetry is relevant regarding new efforts in specific molecular radiotherapy using Auger, CE and beta emitters. Absorbed dose in cells can be obtained by means of the dose per unit cumulated activity (S-values), together with the activity distribution. In this work, Monte Carlo simulation codes PENELOPE and MCNPX were used to obtain cellular S-values for point and extended sources of electrons and beta emitting radionuclides in the nucleus of breast (MDA-MB231, MCF7) and prostate (PC3) cancer cell models.

Monte Carlo mitochondrial dosimetry and microdosimetry of 131I

A mitochondrion is an organelle found in most eukaryotic cells, which produces most of the energy needed by a living cell. It has been shown that ionising radiation causes mitochondrial damage leading to apoptosis or cell death. The aim of this work was to calculate, by Monte Carlo simulation, the specific energy (z) into the mitochondria, due to Auger electrons, conversion electrons and beta emission from (131)I, where the radionuclide was carried by a vector to the cell surface and the surrounding environment. A concentric spherical geometry represents a cell and its nucleus. Three different volumes were used to represent the mitochondria; they were placed in random positions within the cytoplasm. The z produced by a single event is due to low-energy electrons (76 %) and beta particles (24 %) and the mitochondria receive a total mean z two orders of magnitude higher than that of the cell nucleus.

Specific energy from Auger and conversion electrons of 131I, 188Re-anti-CD20 to a lymphocyte's nucleus

The typical radionuclides used to label anti-CD20 in the treatment of non-Hodgkins lymphoma are 90Y, 131I, and 188Re, with the emission of beta particles, Auger electrons, and conversion electrons for the latter two. The aim of the present work was to calculate the contribution of high linear energy transfer radiation as Auger electrons (AE) and conversion electrons (CE) of 131I and 188Re-anti-CD20 to mean specific energy into the cell nucleus by Monte Carlo simulation (MCS), so as to infer therapeutic effectiveness on a dosimetric basis. MCS was used to quantify the frequency–mean specific energy into the cell nucleus, where the cell was modeled by two concentric spheres, considering two cell models. The results showed that 10% and 33% of the mean-specific energies (z¯) per disintegration imparted to the cell nucleus for both geometries are due to AE and CE; on the other hand, if the hit of AE and CE occurs, the contribution to (z¯) is about 64% and 86% for 131I and 188Re, respectively. According to the amount of specific energy from AE and CE into the cell nucleus by positive event, they can cause catastrophic effects in the nuclear DNA in the treatment of non-Hodgkins lymphoma with 131I, 188Re-anti-CD20.

New track-structure Monte Carlo code for 4D ionizing photon transport

ABSTRACT Radiodiagnosis and radiation treatment, in each of their areas such as imaging, radiotherapy and nuclear medicine, require precise calculations about the energy deposited and scattering of the ionizing radiation used. In healthcare applications, it is required to know the penetration and amount of energy deposited in the biological tissue irradiated by ionizing photons; these parameters are function of the photon interaction processes with matter, which can be analyzed experimentally or by Monte Carlo simulation. Purpose: The aim of this work was to develop a new Monte Carlo code for ionizing photon transport in water with the track structure technique, that allows to discriminate primary and secondary photons, and to determine the energy deposited, interaction coordinates, path length and time of flight (TOF) inside of scatter volume. Methods: C++ programming language was used. In the Compton scattering, the polar angle was sampled by methods: Kahn and EGS. Water spheres centered at the origin with different radius were used, where the isotropic point source was placed at (0, 0, 0) for different energies to compute the energy lost by photons and TOF inside spherical volume. Results: It was determined that the best sampling method for the polar angle generation in each Compton interaction was the EGS method. Energy deposited in target region filled with water was compared with MCNPX 2.6 and others’ results from literature. Mean TOF and pathlength inside region of interest was obtained for 4 radii and 5 energies. Conclusions: Quantities computed with the new code are, according to reported data, and so, the new code is reliable for photon transport in water using the track structure method; this will allow the new code to become a useful tool in the areas of radiology and radiation dosimetry. Also, TOF inside scatter volume was reported.

Estimation of the effectiveness ratio (α/β) for resistant cancer cells in U87MG human glioblastoma

Glioblastoma contains self-renewing, tumorigenic cancer stem-like cells that contribute to tumor initiation and therapeutic resistance. The aim of this research was to estimate and compare the effectiveness ratio (α/β) of stem-like cells and differentiated glioma cells derived from the U87MG glioblastoma cell line. Cell survival experiments were obtained in a dose range of 0-20 Gy (13.52 ± 0.09 Gy/h) as a hyperfractionationated accelerated radiotherapy scheme. Biochemical characterization of the post-irradiated cells was performed by flow cytometry analysis and the percentage of stem-like cells that resisted irradiation was determined by the CD133 expression. Results showed that U87MG stem-like cells are highly proliferative and more radioresistant than the U87MG adherent group (with a lesser stem-like character), this in association with the calculated α/β ratio of 17 and 14.1, respectively.

67Ga as a biosensor of iron needs in different organs: Study performed on male and female rats subjected to iron deficiency and exercise

The aim of the present study was to determine the iron needs in different organs and tissues using 67Ga as a biosensor in males and females rats subjected to iron deficiency (ID) and voluntary exercise (EX). 67Ga citrate was injected i.p. to female and male Wistar rats (n=5/sex/group). Groups: Control (sedentary conditions), Control+EX, ID and ID+EX. To determine the 67Ga uptake, samples from the following regions of interest (ROIs) were extracted 12h post-injection: blood, liver, gonads, bone marrow, heart, adrenal glands, skeletal muscle, stomach, kidney, eyeball, sciatic nerve, small intestine and peritoneum. The total 67Ga uptake was 412% higher in ID subjects than in control subjects, being 1011% higher in ID-males than ID-females. In ID-females, the ROIs with the greater 67Ga uptake were blood, kidney and bone marrow, while in ID-males they were sciatic nerve, eyeball and adrenals, which demonstrates that the biodistribution differed between sexes in sedentary conditions but when subjected to EX, the biodistribution was similar in each sex group although females had a greater 67Ga uptake. In ID+EX subjects, the ROIs that showed the highest uptake were sciatic nerve, eyeball and adrenal glands. Using 67Ga as a biosensor, it is possible to identify the needs of iron that each organ requires to perform their functions in normal physiological conditions. In addition, a higher or lower 67Ga uptake in a specific organ may indicate its malfunction or show damage.

Preliminary Analysis of the Social and Scientific Impact of the UAEM‐ININ M.Sc. and D.Sc. Graduate Programme in Medical Physics

Sponsored by the International Atomic Energy Agency (IAEA) in 1994, the Instituto Nacional de Investigaciones Nucleares (ININ) started in Mexico a teaching and training programme (Diplomado) in Radiotherapy Medical Physics. Based on this experience, the Universidad Autonoma del Estado de Mexico (UAEM) and the Instituto Nacional de Investigaciones Nucleares (ININ) launched two years later, the first Graduate Programme in Science (M.Sc. and D.Sc.), specialised in Medical Physics in Mexico. A preliminary analysis of the social and scientific impact of the UAEM‐ININ Programme is presented in this work based on the achievements attained, regarding the number of graduated Medical Physicists, their geographic and academic origin, their current professional activities and the number of scientific publications produced as a result of the thesis, as well as their citations.

Biokinetics and dosimetry of target-specific radiopharmaceuticals for molecular imaging and therapy

Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic or therapeutic applications. 99mTc-HYNIC-TOC has shown high stability both in vitro and in vivo and rapid detection of somatostatin receptor-positive tumors. Therapies using radiolabeled anti-CD20 have demonstrated their efficacy in patients with B-cell non-Hodgkins lymphoma (NHL). The aim of this study was to establish biokinetic models for 99mTc-HYNIC-TOC and 188Re-anti-CD20 and to evaluate their dosimetry as target-specific radiopharmaceuticals. The OLINDA/EXM code was used to calculate patient-specific internal radiation dose estimates. 99mTc-HYNIC-TOC images showed an average tumor/blood ratio of 4.3±0.7 in receptor-positive tumors with an average effective dose of 4.4 mSv. Dosimetric studies indicated that after administration of 5.8 to 7.5 GBq of 188Re-anti-CD20 the absorbed dose to total body would be 0.75 Gy which corresponds to the recommended dose for NHL therapies.