CNN application for automated determination of the patient's size to obtain the size-specific dose estimated in CT.

Introduction. The currently available dosimetry techniques in computed tomography can be inaccurate which overestimate the absorbed dose. Therefore, we aimed to provide an automated and fast methodology to more accurately calculate the SSDE usingDwobtained by using CNN from thorax and abdominal CT study images.Methods. The SSDE was determined from the 200 records files. For that purpose, patients' size was measured in two ways: (a) by developing an algorithm following the AAPM Report No. 204 methodology; and (b) using a CNN according to AAPM Report No. 220.Results. The patient's size measured by the in-house software in the region of thorax and abdomen was 27.63 ± 3.23 cm and 28.66 ± 3.37 cm, while CNN was 18.90 ± 2.6 cm and 21.77 ± 2.45 cm. The SSDE in thorax according to 204 and 220 reports were 17.26 ± 2.81 mGy and 23.70 ± 2.96 mGy for women and 17.08 ± 2.09 mGy and 23.47 ± 2.34 mGy for men. In abdomen was 18.54 ± 2.25 mGy and 23.40 ± 1.88 mGy in women and 18.37 ± 2.31 mGy and 23.84 ± 2.36 mGy in men.Conclusions. Implementing CNN-based automated methodologies can contribute to fast and accurate dose calculations, thereby improving patient-specific radiation safety in clinical practice.

Biokinetics, radiopharmacokinetics and estimation of the absorbed dose in healthy organs due to Technetium-99m transported in the core and on the surface of reconstituted high-density lipoprotein nanoparticles.

The development of rHDL-radionuclide theragnostic systems requires evaluation of the absorbed doses that would be produced in healthy tissues and organs at risk. Technetium-99m is the most widely used radionuclide for diagnostic imaging, therefore, the design of theragnostic reconstituted high density-lipoprotein (rHDL) nanosystems labeled with Technetium-99m offers multiple possibilities. OBJECTIVE: To determine the biokinetics, radiopharmacokinetics and estimate the absorbed doses induced in healthy organs by Technetium-99m transported in the core and on the surface of rHDL. METHODS: Biokinetic and radiopharmacokinetic models of rHDL/[99mTc]Tc-HYNIC-DA (Technetium-99m in the core) and [99mTc]Tc-HYNIC-rHDL (Technetium-99m on the surface) were calculated from their ex vivo biodistribution in healthy mice. Absorbed doses were estimated by the MIRD formalism using OLINDA/EXM and LMFIT softwares. RESULTS: rHDL/[99mTc]Tc-HYNIC-DA and [99mTc]Tc-HYNIC-rHDL show instantaneous absorption in kidney, lung, heart and pancreas, with slower absorption in spleen. rHDL/[99mTc]Tc-HYNIC-DA is absorbed more slowly in the intestine, while [99mTc]Tc-HYNIC-rHDL is absorbed more slowly in the liver. The main target organ for rHDL/[99mTc]Tc-HYNIC-DA, which is hydrophobic in nature, is the liver, whereas the kidney is for the more hydrophilic [99mTc]Tc-HYNIC-rHDL. Assuming that 925 MBq (25 mCi) of Technetium-99m, carried in the core or on the surface of rHDL, are administered, the maximum tolerated doses for the organs of greatest accumulation are not exceeded. CONCLUSION: Theragnostic systems based on 99mTc-labeled rHDL are safe from the dosimetric point of view. The dose estimates obtained can be used to adjust the 99mTc-activity to be administered in future clinical trials.

Photoactivation of Chemotherapeutic Agents with Cerenkov Radiation for Chemo-Photodynamic Therapy.

Cerenkov radiation (CR) can be used as an internal light source in photodynamic therapy (PDT). Methotrexate (MTX) and paclitaxel (PTX), chemotherapeutic agents with wide clinical use, have characteristics of photosensitizers (PS). This work evaluates the possibility of photoexciting MTX and PTX with CR from 18F-FDG to produce reactive oxygen species (ROS) capable of inducing cytotoxicity. PTX did not produce ROS when excited by CR from 18F-FDG, so it is not useful for PDT. In contrast, MTX produces 1O2 (detected by ABMA) in amounts sufficient to significantly decrease the viability of the T47D cells. MTX solutions of 100 nM combined with 18F-FDG activities of 50 (1.85 MBq) and 100 µCi (3.7 MBq) produced a significant decrease in cell viability to (50.09 ± 4.95) and (47.96 ± 11.19)%, respectively, compared to MTX (66.29 ± 5.92)% and 18F-FDG (91.35 ± 7.00% for 50 µCi and 99.43 ± 11.03% for 100 µCi) alone. Using the CellRox Green reagent, the intracellular production of ROS was confirmed as the main mechanism of cytotoxicity. The results confirm the therapeutic potential of photoactivation with CR and the synergy of the combined treatment with chemotherapy + photodynamic therapy (CMT + PDT). The combination of chemotherapeutic agents with PS properties and ß-emitting radiopharmaceuticals, previously approved for clinical use, will make it possible to shorten the evaluation stages of new CMT + PDT systems.

Preclinical evaluation of early multi-organ toxicity induced by liposomal doxorubicin using 67Ga-citrate.

Although liposomal doxorubicin (LPD) is widely used for cancer treatment, knowledge concerning the toxicity induced by this drug in healthy organs and tissues is limited. LPD-induced toxicity studies relative to free doxorubicin (DOX) have focused on cardiotoxicity in tumor-bearing animals. On the other hand, the results on DOX-induced cardiotoxicity depending on gender are controversial. One of the manifestations of toxicity is tissue inflammation. 67Ga-citrate has been used for decades to assess inflammation in various pathologies. In this work, the ex vivo biodistribution of 67Ga-citrate is used to evaluate induced multi-organ toxicity in healthy 10-week-old male and female CD1 mice treated for 5 weeks with LPD. Toxicity in males, determined by 67Ga-citrate, was evident only in the target organs of liposomes (spleen, liver, kidneys, and lungs); the average weight loss was 11% and mortality was 14%. In female mice, 67Ga-citrate revealed a cytotoxic effect in practically all organs, the average weight loss was 37%, and the mortality after the last dose of LPD was 66%. These results confirm the usefulness of 67Ga-citrate and the importance of stratifying by sex in the toxicological evaluation of drugs.

Targeted photodynamic therapy using reconstituted high-density lipoproteins as rhodamine transporters.

Reconstituted high-density lipoprotein (rHDL) nanoparticles are excellent transporters of molecules and very useful for targeted therapy as they specifically recognize the scavenger receptor, class B1 (SR-B1) that is present on the surface of a wide range of tumor cells. However, they have rarely been employed to transport photosensitizers (PS) for photodynamic therapy (PDT). Rhodamine (R) compounds have been dismissed as useful PSs for PDT due to their low 1O2 production, excitation wavelengths with little tissue penetration, and poor selectivity for tumor cells. It was recently demonstrated that when irradiating at 532 nm or with Cerenkov radiation (CR) from a ß-emitting radionuclide, R123, R6G, and RB undergo electron transfer reactions (type I reaction) with folic acid. R6G also produces type I reactions with O2. In this work, the photodynamic effects of the rHDL-R system were evaluated in vitro. rHDL nanoparticles loaded with R123, R6G, and RB were synthesized, and the PS was internalized into T47D tumor cells. When cells were irradiated with a 532-nm laser in the presence of an rHDL-R systems, a cytotoxic photodynamic effect was obtained in the order R6G > R123 > RB. In the presence of CR from a 177Lu source, cytotoxicity showed the order R6G > RB > R123. The higher cytotoxicity induced by R6G in both cases corresponds to higher cellular internalization and larger production of type I and II reactions. Thus, in this work, it is proposed that rHDL-R/177Lu system can be applied in theragnostics as a multimodal radiotherapy-PDT-imaging system (imaging by SPECT or Cerenkov) and in hypoxic solid tumors in which external radiation is not effective and 177Lu-CR acts as light source.

A Multimodal Theranostic System Prepared from High-Density Lipoprotein Carrier of Doxorubicin and 177Lu.

Recently, it was demonstrated that doxorubicin (Dox.HCl), a chemotherapeutic agent, could be photoactivated by Cerenkov radiation (CR). The objective of the present work was to develop a multimodal chemotherapy-radiotherapy-photodynamic therapeutic system based on reconstituted high-density lipoprotein (rHDL) loaded with Dox.HCl and 177Lu-DOTA. 177Lu acts as a therapeutic radionuclide and CR source. The system can be visualized by nuclear imaging. Fluorescence microscopy showed that rHDL-Dox specifically recognized cancer cells (T47D) that are positive for SR-B1 receptors. Encapsulated Dox.HCl was released into the cells and produced reactive oxygen species when irradiated with a 450-nm laser (photodynamic effect). The same effect occurred when Dox.HCl was irradiated by 177Lu CR. Through in vitro experiments, it was confirmed that the addition of 177Lu-DOTA to the rHDL-Dox nanosystem did not affect the specific recognition of SR-B1 receptors expressed in cells, or the cellular internalization of 177Lu-DOTA. The toxicity induced by the rHDL-Dox/177Lu nanosystem in cell lines with high (T47D and PC3), poor (H9C2) and almost-zero (human fibroblasts (FB)) expression of SR-B1 was evaluated in vitro and confirmed the synergy of the combined chemotherapy-radiotherapy-photodynamic therapeutic effect; this induced toxicity was proportional to the expression of the SR-B1 receptor on the surface of the cells used. The HDL-Dox/177Lu nanosystem experienced uptake by tumor cells and the liver-both tissues with high expression of SR-B1 receptors-but not by the heart. 177Lu CR offered the possibility of imparting photodynamic therapy where laser light could not reach.

Evaluation of doxorubicin-induced early multi-organ toxicity in male CD1 mice by biodistribution of 18F-FDG and 67Ga-citrate. Pilot study.

The search for methods that identify early toxicity, induced by chemotherapy, is urgent. Changes in the biodistribution of radiopharmaceuticals could give information on early toxicity. Ten-week-old CD1 male mice were divided into four groups. Two groups were administered a weekly dose of 5 mg/kg of doxorubicin hydrochloride (DOX) for 5 weeks and the control groups were administered saline solution. One week after the end of treatment, the biodistribution of 18F-FDG and 67Ga-citrate were carried out, as was the quantification of plasma enzymes CK, CK-MB, LDH and AST. All enzymes were higher in the treated animals, but only significant (p < 0.05) in the case of CK-MB. 18F-FDG uptake increased in all organs of treated animals except retroperitoneal fat, being significant in spleen, brain, heart, liver, lung, kidney, and inguinal fat. 67Ga-citrate had a more complex pattern. The uptake in the DOX group was higher in spleen, lung, kidney, testes, and gonadal fat, it did not change in brain, heart, and liver, and it was lower in the rest of the organs. It only showed significant differences in lung and pancreas. A thorough discussion of the possible causes that produced the change in biodistributions of both radiopharmaceuticals is included. The pilot study showed that both radiopharmaceuticals could identify early multi-organ toxicity induced by DOX. Although 18F-FDG seems to be better, 67Ga-citrato should not be ruled out a priori. The detection of early toxicity would serve to adopt treatments that prevent its progression, thus improving patient's quality of life.

Femur absorptiometry changes determined by X-ray image segmentation in mice under experimental diabetes and ovariectomy.

AIM: The aim of the present work was to determine if both ovariectomy (OVX) and type 2 diabetes mellitus (T2DM) can change X-ray absorptiometry until reach the osteoporosis condition. RESULTS: The segmentation allowed us to quantitatively determine the X-ray absorption in the femurs of mice subjected to OVX, T2DM and both pathologies together. CONCLUSIONS: The test subjects suffering from the mentioned pathologies separately or together, did not reach the osteoporosis condition when they were 30 weeks old.

In vitro irradiation of doxorubicin with 18F-FDG Cerenkov radiation and its potential application as a theragnostic system.

Doxorubicin (DOX), an effective chemotherapeutic agent, has a wide excitation band centred at 480 nm. Cerenkov radiation (CR) is considered an internal light source in photodynamic therapy (PDT). DOX could be photoactivated by CR and thus, enhancing its cytotoxicity. In this work, 18F-FDG was used to evaluate the effect of Cerenkov radiation on DOX, in comparison to irradiation with a 450-nm laser beam, in terms of ROS production. The production of 1O2 and O2⁎- reactive species during DOX irradiation was detected indirectly by ABMA and DCPIP bleaching, respectively. The cytotoxic effect of the DOX / 18F-FDG CR system was evaluated in the T47D breast cancer cell line. The irradiation of DOX produced 1O2 and O2⁎- species using both 18F-FDG CR and a 450-nm laser beam. The majority reactive species produced in both cases was 1O2; a favourable result, given the greater cytotoxicity of this species. The viability of T47D cells in presence of DOX (5 nM), 18F-FDG (37.5 µCi) and DOX (5 nM)/18F-FDG (37.5 µCi) was (86 ± 9)%, (84 ± 8)% and (64 ± 5)%, respectively; these results suggest a synergistic cytotoxic effect derived from the cytotoxic activity of DOX and its photoactivation by 18F-FDG CR. It is worth noting that the system could be optimized in terms of DOX concentration and 18F-FDG activity for better results. Due to the fact that 18F-FDG is widely used in nuclear imaging, the DOX/18F-FDG system also possesses theragnostic characteristics. Thus, in this work, it is demonstrated that DOX can be used in a dual therapy system based on chemotherapy-PDT when 18F-FDG CR is used as a DOX excitation source.

Effects of chronic immobilization stress on biokinetics and dosimetry of 67Ga in a murine model.

The aim of this work is to determine the effect of chronic immobilization stress on kinetics and dosimetry of 67Ga in a mouse model. A control group (CG) and a stress group (SG), each with 15 mice, were included in the study, and the latter group was subjected to a chronic immobilization stress model 2 h daily for 14 consecutive days. At day 13, 67Ga-citrate was administered intraperitoneally (11.24 ± 0.44 MBq) to each mouse. Then, sets of three mice were obtained sequentially at 24, 36, 48, 60 and 72 h, in which the radionuclide activity was measured with an activity counter. The 67Ga biokinetic data showed a fast blood clearance in the SG, with a mean residence time of 0.06 h. The calculated mean radiation absorbed doses were: liver (2.45 × 10-03 Gy), heart (3.17 × 10-04 Gy) and kidney (1.88 × 10-04 Gy) in the SG. The results show that stress reduced weight gain by approximately 13% and also increased adrenal gland weight by 26%. On the other hand, chronic stress accelerates 67Ga clearance after 24 h compared to normal conditions. It is concluded that murine organisms under chronic immobilization stress have higher gallium-67 clearance rates, decreasing the cumulated activity and absorbed dose in all organs.

Theoretical and experimental characterization of emission and transmission spectra of Cerenkov radiation generated by 177Lu in tissue.

Cerenkov radiation (CR) is the emission of UV-vis light generated by the de-excitation of the molecules in the medium, after being polarized by an excited particle traveling faster than the speed of light. When ß particles travel through tissue with energies greater than 219 keV, CR occurs. Tissues possess a spectral optical window of 600 to 1100 nm. The CR within this range can be useful for quantitative preclinical studies using optical imaging and for the in-vivo evaluation of Lu177-radiopharmaceuticals (ß-particle emitters). The objective of our research was to determine the experimental emission light spectrum of Lu177-CR and evaluate its transmission properties in tissue as well as the feasibility to applying CR imaging in the preclinical studies of Lu177-radiopharmaceuticals. The theoretical and experimental characterizations of the emission and transmission spectra of Lu177-CR in tissue, in the vis-NIR region (350 to 900 nm), were performed using Monte Carlo simulation and UV-vis spectroscopy. Mice Lu177-CR images were acquired using a charge-coupled detector camera and were quantitatively analyzed. The results demonstrated good agreement between the theoretical and the experimental Lu177-CR emission spectra. Preclinical CR imaging demonstrated that the biokinetics of Lu177-radiopharmaceuticals in the main organs of mice can be acquired.

Effect of 177Lu-iPSMA on viability and DNA damage of human glioma cells subjected to hypoxia-mimetic conditions.

The therapeutic potential of 177Lu-iPSMA on hypoxic cancer cells has not been yet demonstrated. The aim of this work was to evaluate the radiation dose effect of 177Lu-iPSMA on viability and DNA damage in U87MG human glioma cells subjected to hypoxia-mimetic conditions. U87MG cells treated with 177Lu-iPSMA were incubated with CoCl2 in order to induce hypoxia-mimetic conditions. The cytotoxic and genotoxic effect was evaluated with an in vitro viability test and a neutral comet assay. 177Lu-iPSMA decreased the cell viability and induced DNA double strand breaks in U87MG human glioma cells under hypoxia-mimetic conditions. 177Lu-iPSMA produced the maximum effect at 48 h, suggesting that this radiopharmaceutical could be used as a strategy for the treatment of human glioma hypoxic cells.

Differences in the S value between male and female murine model for diagnostic, therapeutic and theragnostic radionuclides.

The aim of this work was to calculate S values for 99mTc, 67Ga, 68Ga, 18F, 223Ra, 166Ho, 90Y, 161Tb 131I and 177Lu, using a mouse phantom (MOBY) standard and considering the anatomic sizes from males and females, the simulation of radiation transport was performed with GATE/Geant4 platform. This indicates that in the internal dosimetry the use of a customized geometry is relevant for each gender and a standard model is not a good choice.

Estimation of the effectiveness ratio (α/ß) 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/ß) 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/ß ratio of 17 and 14.1, respectively.

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.

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.

Multifunctional targeted therapy system based on (99m) Tc/(177) Lu-labeled gold nanoparticles-Tat(49-57)-Lys(3) -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.

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.

¹5³Sm-HM for arthritic knee pain. Estimated dosimetry.

Osteoarthritis is the most common type of arthropathy and after cardiovascular diseases is the most disabling disease in developing countries. The dosimetry for the clinical application of 153-samarium-hydroxymacroaggregates (¹5³Sm-HM) for radiation synovectomy (RSV) and palliative treatment for arthritic pain, as far as we know, has not been reported. The aim of this research was to estimate the radiation dose necessary for synovial ablation and pain palliation with minimum risk to the patient. ¹5³Sm-HM (370 MBq) was administered intra-articularly in a patient with severe knee pain and hindered motility. Regions of interest drawn on sequential, conjugated, anterior and posterior scintigraphy images were used to obtain the respective activity. The data was entered into a knee joint histological-geometric model designed with micrometric dimensions to represent the synovial cell layers. The Monte Carlo code was used to calculate the absorbed dose in each of the 12 model-cells representing the distance from the synovial liquid to the cartilage or bone. The absorbed dose in the synovial cavity was 114 Gy which is sufficient energy for RSV. The treated patient referred little pain and higher motility with no adverse reactions. ¹5³Sm-HM is a potentially valid radiopharmaceutical for RSV, which effectively palliates knee pain.

Biokinetics and dosimetry of 188Re-anti-CD20 in patients with non-Hodgkin's lymphoma: preliminary experience.

BACKGROUND: Radioimmunotherapy is a molecular targeting treatment for high-risk leukemia and lymphoma. Rhenium-188-labeled anti-CD66 monoclonal antibody has been used successfully in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome. Our aim was to establish the biokinetics of (188)Re-anti-CD20 in patients and to evaluate its dosimetry as a target-specific radiopharmaceutical for non-Hodgkin's lymphoma (NHL) radioimmunotherapy. METHODS: Whole-body images were acquired at various times after administration of (188)Re-anti-CD20, obtained from instant freeze-dried kit formulations with radiochemical purity >95%. Regions of interest (ROIs) were drawn around source organs in each time frame. The cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate time-activity curves in each organ to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. RESULTS: Dosimetric studies indicated that after administration of 4.87-8.72 GBq of (188)Re-anti-CD20, the absorbed dose to total body would be 0.75 Gy, which corresponds with the recommended dose for NHL therapies. CONCLUSIONS: The calculated absorbed doses of (188)Re-anti-CD20 indicate that it may be used in radioimmunotherapy. Therefore, these preliminary data justify a full assessment of the safety, toxicity, and efficacy of (188)Re-anti-CD20 in a clinical study.