J. Rodríguez-Cortés

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpam, Mexico City, Mexico

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Publications (4)3.44 Total impact

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    ABSTRACT: Malignant pancreatic tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to determine biokinetic parameters in mice, in order to estimate the induced pancreatic tumour absorbed doses and to evaluate an `in house' 177Lu-DOTA-TATE radiopharmaceutical as part of preclinical studies for targeted therapy in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (nD22) to obtain biokinetic and dosimetric data of 177Lu-DOTA-TATE. The mean tumour uptake 2 h post injection was 14.76±1.9% I.A./g; kidney and pancreas uptake, at the same time, were 7.27±1.1% I.A./g (1.71±0.90%/organ) and 4.20±0.98% I.A./g (0.42±0.03%/organ), respectively. The mean absorbed dose to tumour, kidney and pancreas was 0.58±0.02 Gy/MBq; 0.23±0.01 Gy/MBq and 0.14±0.01 Gy/MBq, respectively. These studies justify further dosimetric estimations to ensure that 177Lu-DOTA-TATE will act as expected in humans.
    No preview · Article · Oct 2007 · Radiation Effects and Defects in Solids
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    ABSTRACT: Radiolabelled peptides have been used as target-specific radiopharmaceuticals. The goal of this research was the in vitro assessment of the uptake, internalization, externalization, and efflux of five radiolabelled peptides in cancer cells to estimate radiation-absorbed doses from experimental biokinetic data. 177Lu-DOTA-octreotate, 188Re-lanreotide, and 99mTc-HYNIC-octreotide were studied in the AR42J cell line. The PC3 and NCIH69 cells were used for 99mTc-HYNIC-bombesin and 177Lu-DOTA-minigastrin, respectively. The cumulated activities in the membrane and cytoplasm were calculated by integration of the experimental time–activity curves and used for dosimetry calculations according to the Medical Internal Radiation Dose (MIRD) cellular methodology. The mean absorbed dose to the cell nucleus were 0.69±0.09, 0.11±0.08, 0.55±0.09, 3.45±0.48, and 3.30±0.65 Gy/Bq for 99mTc-HYNIC-bombesin, 99mTc-HYNIC-octreotide, 177Lu-DOTA-minigastrin, 177Lu-DOTA-octreotate, and 188Re-lanreotide, respectively. If radiopharmaceutical cell kinetics were not used and only uptake data were considered, the calculated doses would be overestimated up to 25 times.
    No preview · Article · Sep 2007 · Radiation Effects and Defects in Solids
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    ABSTRACT: Antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. (99m)Tc-UBI labeled by a direct method has shown high in vitro and in vivo stability, specific uptake at the site of infection, rapid background clearance, minimal accumulation in non-target tissues and rapid detection of infection sites in mice. The aim of this study was to establish a (99m)Tc-UBI biokinetic model and evaluate its feasibility as an infection imaging agent in humans. Whole-body images from 6 children with suspected bone infection were acquired at 1, 30, 120, 240 min and 24 h after (99m)Tc-UBI administration. Regions of interest (ROIs) were drawn around source organs (heart, liver, kidneys and bladder) on each time frame. The same set of ROIs was used for all 6 scans and the cpm of each ROI were converted to activity using the conjugate view counting method. Counts were corrected by physical decay and by the background correction factor derived from preclinical phantom studies. The image sequence was used to extrapolate (99m)Tc-UBI time-activity curves in each organ and calculate the cumulated activity (A). Urine samples were used to obtain the cumulative percent of injected activity (% I.A.) versus time renal elimination. The absorbed dose in organs was evaluated according to the general equation described in the MIRD formalism. In addition, (67)Ga-citrate images were obtained from all the patients and used as a control. Biokinetic data showed a fast blood clearance with a mean residence time of 0.52 h. Approximately 85% of the injected activity was eliminated by renal clearance 24 h after (99m)Tc-UBI administration. Images showed minimal accumulation in non-target tissues with an average target/non-target ratio of 2.18 +/- 0.74 in positive lesions at 2 h. All infection positive(99m)Tc-UBI images were in agreement with those obtained with (67)Ga-citrate. The mean radiation absorbed dose calculated was 0.13 mGy/MBq for kidneys and the effective dose was 4.34 x 10(-3)mSv/MBq.
    No preview · Article · May 2004 · Nuclear Medicine and Biology
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    ABSTRACT: Recently, antimicrobial peptides have been proposed as new agents to distinguish between bacterial infections and sterile inflammatory processes. Based on these considerations, Ubiquicidin peptide 29-41 (UBI) has been labeled with 99mTc using a new direct method showing a radiochemical purity > 97 %, high stability in human serum, and low protein binding. In addition 99mTc-UBI showed a specific in vitro and in vivo binding to bacteria. However its biokinetic parameters have not been evaluated since it is one of the new generation radiopharmaceuticals based on peptide structures. Therefore the aim of this project was to establish the biokinetic model for 99mTc-UBI. An activity from 74 to 148 MBq was injected to patients with bone infection and 5 whole body scans were taken at 1, 30, 120, 240 min and 24 h after radiopharmaceutical administration, with a dual head scanner. Urine was collected for 24 h. An antropomorphic phantom was previously used to calculate the effect of attenuation and scattered radiation on the gamma camera acquisition images. ROIs of the selected organs in patients (kidney, liver, heart, bone, soft tissue and lesion) were drawn, and attenuation and scatter corrected. The % urine elimination at 24 h and time integrated ROIs (cpm/pixel/ROIs) were used to obtain the residence time (tau) in each tissue and to establish the biokinetic model. Pharmacokinetic data show that blood clearance is biexponential with a mean residence time in the central compartment of 0.52 h. The images showed non-accumulation in metabolic organs. More than 75 % of the injected activity was eliminated by renal clearance 4 h after 99mTc-UBI administration. The mean radiation dose calculated according to the MIRD formalism was 0.130 mGy/MBq for kidney and the effective dose was 4.29 × 10-3 mSv/MBq.
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