Absorbed dose evaluation at different organs after 131I oral contamination of two Wistar rat models

Iodine-131 (131I) is one of the most frequently used radionuclides for diagnosis and therapy of thyroid diseases. It is administered orally in the treatment of cancer to eliminate the residual postoperative microscopic tumor foci, and the residual normal thyroid tissue for early detection of recurrence [1]. The comparative behavior of 131I concentration into two animalmodels with total and partial thyroid has been investigated in our previous work [2]. The accumulated activities have been measured in fourteen organs. In this study, the mean absorbed doses resulting from 131I accumulated in all organs have been evaluated using RODES software [3, 4]. With this software, mean absorbed doses were calculatedfor selected organs (thyroid, lungs, heart, liver, kidneys, stomach, spleen, large and small intestine, testes, urinary bladder wall) by combining the specific absorbed fractions (SAF) of energy with radiation emission spectra and biokinetic data determined from our previous experimental study [2]. Calculations were based on the 131I photon and electron emissions reported by [5] and SAFs previously calculated by Monte Carlo simulation in the voxel phantom of an adult male rate [3, 4]. The obtained results show high absorbed dosesdeliveredto stomach and lungs for both models compared to other organs. The dose received by the testes and salivary glands is found to be higher in the case of the rat model without thyroid. Conversely, the spleen and bladder wall received lower doses in this latter model compared to those received by the rat model with thyroid. One can also note that the difference in mean absorbed dose received by liver, lungs, heart, and walls of the stomach is not significant between the two rat models.

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Histological long-term effects in relevant tissues after 131I contamination of two Wistar rat models

BIO Web of Conferences ◽

10.1051/bioconf/20191405009 ◽

2019 ◽

Vol 14 ◽

pp. 05009

Author(s):

Meriem Mezaguer-Lekouaghet ◽

Abdelwahab Badreddine ◽

Saadia Mameri ◽

Maamar Souidi ◽

Ahcène Baz ◽

...

Keyword(s):

Biological Effects ◽

Thyroid Tissue ◽

Absorbed Dose ◽

Wistar Rat ◽

Tissue Analysis ◽

Long Term Effects ◽

Target Organs ◽

Thyroid Mass ◽

Iodine 131

Procedures using iodine-131 (131I) represent about 90% of all therapies in nuclear medicine [1, 2]. It is important to evaluate the long-term biological effects of 131I treatment on non-target organs in order to improve the patient radioprotection. The aim of this work is to use an experimental animal model to contribute to the understanding of some biological effects induced by 131I contamination, and especially histological effects. Two models of Wistar rats with (Tr+) and without thyroid (Tr-) were orally contaminated with iodine and after 8 months they were sacrificed and the histological effects on some relevant tissues such as thyroid, testes, liver and kidneys were been studied. Thyroid tissue analysis revealed that in the case of the Tr+ model compared to their control (Tr+ uncontaminated), 50% of the slides examined had remodeled the thyroid tissue with rare follicles choked by fibrosis and with epithelial changes. However, for Tr- compared to their control, the examined slides reveal the presence of a small, completely atrophied thyroid mass associated with vesicular fibrosis and with detachment of the colloid. For the renal organ, disturbances are observed: inflammation of the presence of tissue fibrosis and glomerular necrosis. For the liver, there is an appearance of inflammatory focus in different degrees around the portals. However, the results of the testes of both models compared to their controls revealed no histological abnormalities. The observed histological effects are correlated with the corresponding absorbed dose received by each organ and calculated using the RODES software [3, 4].

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The Nonimpact of Thyroid Stunning: Remnant Ablation Rates in 131I-Scanned and Nonscanned Individuals

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.8.7717 ◽

2001 ◽

Vol 86 (8) ◽

pp. 3507-3511 ◽

Cited By ~ 32

Author(s):

Lilah F. Morris ◽

Alan D. Waxman ◽

Glenn D. Braunstein

Keyword(s):

Initial Treatment ◽

Thyroid Tissue ◽

Absorbed Dose ◽

Remnant Ablation ◽

Metastatic Lesions ◽

Therapeutic Outcomes ◽

Treatment Dose ◽

Nonsignificant Difference ◽

The Difference ◽

Thyroid Stunning

Thyroid stunning has been reported as the temporary impairment of thyroid tissue after a 111-MBq or greater diagnostic 131I dose that decreases the final absorbed dose in ablative therapy. Concerns regarding the reality of stunning have arisen in part due to a flawed study design in prior reports. To assess whether a stunning effect has any impact on therapeutic outcomes, we compared initial treatment ablation rates in patients who received 111- to 185-MBq 131I diagnostic scans (n = 37) before ablative doses of 3700–7400 MBq with ablation rates in patients who did not receive any 131I before the initial treatment dose (n = 63). Ablation rates were 64.9% for scanned patients and 66.7% for nonscanned patients, a nonsignificant difference. Nonscanned patients with metastatic lesions (n = 23) were ablated at a higher rate (78.3%) than scanned patients (n = 9) (66.7%), but the difference was not significant (P = 0.50). It is possible that the reported stunning phenomenon, specifically its impact in temporarily impairing tissue, has been overemphasized.

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Differences in Rat Models Used in Routine Toxicity Studies

International Journal of Toxicology ◽

10.1177/1091581810391818 ◽

2011 ◽

Vol 30 (2) ◽

pp. 162-173 ◽

Cited By ~ 30

Author(s):

Klaus Weber ◽

Tanja Razinger ◽

Jerry F. Hardisty ◽

Peter Mann ◽

Kellie C. Martel ◽

...

Keyword(s):

Body Weight ◽

Rat Model ◽

Wistar Rat ◽

Historical Background ◽

Housing Conditions ◽

Sprague Dawley ◽

Rat Models ◽

Toxicity Studies ◽

Background Data ◽

Age Dependent

The discussion on whether the Sprague Dawley (SD), the Fischer F344, or the Hannover Wistar rat is the most appropriate model for toxicity studies in rodents is ongoing. A substantial quantity of data on these strains concerning their source, diet, and housing conditions have been published. Generally, before starting a toxicology program in rodents, it should be taken into account that oncogenicity studies will be required for the majority of compounds successfully completing development. Survival, body weight development, incidence, type, time of onset of age-dependent lesions and neoplasms, as well as some special considerations of the rat model selected may be decisive. Therefore, an understanding of the historical background data is essential. These aspects demonstrate why the use of a specific rat model should be carefully considered at the beginning of the toxicology program.

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Clinical implementation of PLANET®Dose for dosimetric assessment after [177Lu]Lu-DOTA-TATE : comparison with Dosimetry Toolkit® and OLINDA/EXM® V1.0

10.21203/rs.3.rs-36998/v2 ◽

2020 ◽

Author(s):

Lore Santoro ◽

Laurine Pitalot ◽

Dorian Trauchessec ◽

Erick Mora-Ramirez ◽

Pierre-Olivier Kotzki ◽

...

Keyword(s):

At Risk ◽

Organs At Risk ◽

Absorbed Dose ◽

Peptide Receptor Radionuclide Therapy ◽

Slight Variation ◽

Clinical Implementation ◽

Absorbed Doses ◽

Plot Analysis ◽

The Difference ◽

Over Time

Abstract Background: The aim of this study was to compare a commercial dosimetry workstation (PLANET®Dose) and the dosimetry approach (GE Dosimetry Toolkit® and OLINDA/EXM® V1.0) currently used in our department for quantification of the absorbed dose in organs at risk after peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE. Methods: An evaluation on phantom was performed to determine the SPECT calibration factor variations over time and to compare the Time Integrated Activity Coefficients (TIACs) and absorbed doses obtained with the two tools. Then, the two tools were used for dosimetry evaluation in 21 patients with neuroendocrine tumours after the first and second injection of 7.2 ± 0.2 GBq of [177Lu]Lu-DOTA-TATE (40 dosimetry analyses with each software). SPECT/CT images were acquired at 4h, 24h, 72h and 192h after [177Lu]Lu-DOTA-TATE injection and were reconstructed using the Xeleris software (General Electric). The liver, spleen and kidney masses, TIACs and absorbed doses were calculated using i) GE Dosimetry Toolkit® (DTK) and OLINDA/EXM® V1.0 and ii) the Local Deposition Method (LDM) or Dose voxel-Kernel convolution (DK) on PLANET®Dose. Results: With the phantom, the 3D calibration factors showed a slight variation (0.8% and 3.3%) over time and TIACs of 225.19h and 217.52h were obtained with DTK and PLANET®Dose, respectively. In patients, the root mean square deviation value was 8.9% for the organ masses, 8.1% for the TIACs, and 9.1 and 7.8% for the absorbed doses with LDM and DK, respectively. The Lin’s concordance correlation coefficient was 0.99 and the Bland-Altman plot analysis estimated that the difference of absorbed dose values between methods ranged from -0.75 Gy to 0.49 Gy, from -0.20 Gy to 0.64 Gy and from -0.43 to 1.03 Gy for approximately 95% of the 40 liver, kidneys and spleen dosimetry analyses. A difference of 2.2% was obtained between the absorbed doses to organs at risk calculated with LDM and DK. Conclusions: The absorbed doses to organs at risk obtained with the new workstation are concordant with those calculated with the currently used software and in agreement with the literature. These results validate the use of PLANET®Dose in clinical routine for patient dosimetry after targeted radiotherapy with [177Lu]Lu-DOTA-TATE.

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Clinical Implementation of PLANET®Dose for Dosimetric Assessment after 177Lu-DOTATATE: Comparison with Dosimetry Toolkit® and OLINDA/EXM® V1.0

10.21203/rs.3.rs-36998/v1 ◽

2020 ◽

Author(s):

Lore Santoro ◽

Laurine Pitalot ◽

Dorian Trauchessec ◽

Erick Mora-Ramirez ◽

Pierre-Olivier Kotzki ◽

...

Keyword(s):

At Risk ◽

Organs At Risk ◽

Absorbed Dose ◽

Peptide Receptor Radionuclide Therapy ◽

Slight Variation ◽

Clinical Implementation ◽

Absorbed Doses ◽

Relative Standard ◽

The Difference ◽

Over Time

Abstract Background: Recently, commercial software tools have become available for dosimetry evaluations in clinical settings. The aim of this study was to compare a commercial dosimetry workstation (PLANETâDose) and the dosimetry approach (GE Dosimetry Toolkit® and OLINDA/EXM® V1.0) currently used in our department for quantification of the absorbed dose in organs at risk after peptide receptor radionuclide therapy with 177Lu-DOTATATE.Methods: First, an evaluation on phantom, with data acquisition at 5 time points, was performed to determine the SPECT calibration factor variations over time and to compare the Time Integrated Activity Coefficients (TIACs) and absorbed doses obtained with the two tools. Then, the two tools were used for dosimetry evaluation in 21 patients with neuroendocrine tumours after the first and second injection of 7.2 ± 0.2 GBq of 177Lu-DOTATATE (40 dosimetry analyses with each software). SPECT/CT images were acquired at 4h, 24h, 72h and 192h after 177Lu-DOTATATE injection and were reconstructed using the Xeleris software (General Electric). The liver, spleen and kidney masses, TIACs and absorbed doses were calculated using i) GE Dosimetry Toolkit® (DTK) and OLINDA/EXM® V1.0 and ii) the Local Deposition Method (LDM) or Dose voxel-Kernel convolution (DK) on PLANETâDose. Results: With the phantom, the 3D calibration factors showed a slight variation (0.8% and 3.3%) over time and TIACs of 225.19h and 217.52h were obtained with DTK and PLANETâDose, respectively. In patients, the mean of the relative standard deviations was -1% for the organ masses, 5.6%, for the TIACs, and 4.4% for the absorbed doses. The Lin’s concordance correlation coefficient was 0.99 and the Bland-Altman plot analysis estimated that the difference of absorbed dose values between methods ranged from -0.58 Gy to 0.84 Gy for approximately 95% of the 40 dosimetry analyses. A difference of 2.2% was obtained between the absorbed doses to organs at risk calculated with LDM and DK (PLANETâDose). Conclusions: The absorbed doses to organs at risk obtained with the new workstation are concordant with those calculated with the currently used software and in agreement with the literature. These results validate the use of PLANETâDose in clinical routine for patient dosimetry after targeted radiotherapy with 177Lu-DOTATATE.

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Biodistribution and post-therapy dosimetric analysis of [177Lu]Lu-DOTAZOL in patients with osteoblastic metastases: first results

EJNMMI Research ◽

10.1186/s13550-019-0566-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Ambreen Khawar ◽

Elisabeth Eppard ◽

Frank Roesch ◽

Hojjat Ahmadzadehfar ◽

Stefan Kürpig ◽

...

Keyword(s):

Urinary Bladder ◽

Radionuclide Therapy ◽

Bladder Wall ◽

Absorbed Dose ◽

Whole Body ◽

Normal Organ ◽

Skeletal Disease ◽

Absorbed Doses ◽

Urinary Bladder Wall ◽

Dosimetric Analysis

Abstract Background Preclinical biodistribution and dosimetric analysis of [177Lu]Lu-DOTAZOL suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [177Lu]Lu-DOTAZOL in patients with metastatic skeletal disease. Method Four patients with metastatic skeletal disease (age range, 64–83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.3 mCi) of [177Lu]Lu-DOTAZOL. Biodistribution was assessed with serial planar whole body scintigraphy at 20 min and 3, 24, and 167 h post injection (p.i.) and blood samples at 20 min and 3, 8, 24, and 167 h p.i. Percent of injected activity in the blood, kidneys, urinary bladder, skeleton, and whole body was determined. Bone marrow self-dose was determined by an indirect blood-based method. Urinary bladder wall residence time was calculated using Cloutier’s dynamic urinary bladder model with a 4-h voiding interval. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) software was used to determine residence times in source organs by applying biexponential curve fitting and to calculate organ absorbed dose. Results Qualitative biodistribution analysis revealed early and high uptake of [177Lu]Lu-DOTAZOL in the kidneys with fast clearance showing minimal activity by 24 h p.i. Activity in the skeleton increased gradually over time. Mean residence times were found to be highest in the skeleton followed by the kidneys. Highest mean organ absorbed dose was 3.33 mSv/MBq for osteogenic cells followed by kidneys (0.490 mSv/MBq), red marrow (0.461 mSv/MBq), and urinary bladder wall (0.322 mSv/MBq). The biodistribution and normal organ absorbed doses of [177Lu]Lu-DOTAZOL are consistent with preclinical data. Conclusion [177Lu]Lu-DOTAZOL shows maximum absorbed doses in bone and low kidney doses, making it a promising agent for radionuclide therapy of bone metastasis. Further studies are warranted to evaluate the efficacy and safety of radionuclide therapy with [177Lu]Lu-DOTAZOL in the clinical setting.

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Biodistribution and Radiation Dosimetric Analysis of [68Ga]Ga-RM2: A Potent GRPR Antagonist in Prostate Carcinoma Patients

Radiation ◽

10.3390/radiation1010004 ◽

2020 ◽

Vol 1 (1) ◽

pp. 33-44

Author(s):

Matthias Haendeler ◽

Ambreen Khawar ◽

Hojjat Ahmadzadehfar ◽

Stefan Kürpig ◽

Michael Meisenheimer ◽

...

Keyword(s):

Urinary Bladder ◽

Prostate Carcinoma ◽

Bladder Wall ◽

Absorbed Dose ◽

Stomach Wall ◽

Physiological Uptake ◽

Absorbed Doses ◽

Pet Tracer ◽

Red Marrow ◽

Positron Emission

[68Ga]Ga-RM2 is a promising innovative positron emission tomography (PET) tracer for patients with primary or metastatic prostate carcinoma. This study aims to analyze the biodistribution and radiation dosimetry of [68Ga]Ga-RM2 in five prostate cancer patients. The percentages of injected activity in the source organs and blood samples were determined. Bone marrow residence time was calculated using an indirect blood-based method. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) was used to determine residence times, organ absorbed and effective doses. Physiological uptake was seen in kidneys, urinary bladder, pancreas, stomach, spleen and liver. Blood clearance was fast and followed by rapid clearance of activity from kidneys resulting in high activity concentrations in the urinary bladder. The urinary bladder wall was the most irradiated organ with highest mean organ absorbed dose (0.470 mSv/MBq) followed by pancreas (0.124 mSv/MBq), stomach wall (0.063 mSv/MBq), kidneys (0.049 mSv/MBq) and red marrow (0.010 mSv/MBq). The effective dose was found to be 0.038 mSv/MBq. Organ absorbed doses were found to be comparable to other gallium-68 labelled GRPR antagonists and lower than [68Ga]Ga-PSMA with the exception of the urinary bladder, pancreas and stomach wall. Remarkable interindividual differences were observed for the organ absorbed doses. Therefore, [68Ga]Ga-RM2 is a safe diagnostic agent with a significantly lower kidney dose but higher pancreas and urinary bladder doses as compared to [68Ga]Ga-PSMA.

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Evaluation of the biochemical and anti-snake venom effects of Calliandra portoricensis extract fractions in wistar rat models

Planta Medica ◽

10.1055/s-0032-1320624 ◽

2012 ◽

Vol 78 (11) ◽

Author(s):

PE Ebong ◽

HP Onyeama ◽

MU Eteng ◽

GO Igile ◽

GE Egbung

Keyword(s):

Snake Venom ◽

Wistar Rat ◽

Rat Models

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α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05170-6 ◽

2021 ◽

Author(s):

S. Schumann ◽

U. Eberlein ◽

C. Lapa ◽

J. Müller ◽

S. Serfling ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Damage ◽

Cancer Patients ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Absorbed Dose ◽

Peripheral Blood Mononuclear ◽

Absorbed Doses ◽

Blood Mononuclear Cells

Abstract Purpose One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. Methods Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. Results The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h – 4 weeks after administration), the α-track frequency remained elevated. Conclusion The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.

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Engineered Stem Cells Improve Neurogenic Bladder by Overexpressing SDF-1 in a Pelvic Nerve Injury Rat Model

Cell Transplantation ◽

10.1177/0963689720902466 ◽

2020 ◽

Vol 29 ◽

pp. 096368972090246 ◽

Cited By ~ 2

Author(s):

Guan Qun Zhu ◽

Seung Hwan Jeon ◽

Kyu Won Lee ◽

Hyuk Jin Cho ◽

U-Syn Ha ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Neurogenic Bladder ◽

Rat Model ◽

Bladder Wall ◽

Bladder Function ◽

Pelvic Nerve ◽

Injured Nerve

There is still a lack of sufficient research on the mechanism behind neurogenic bladder (NB) treatment. The aim of this study was to explore the effect of overexpressed stromal cell-derived factor-1 (SDF-1) secreted by engineered immortalized mesenchymal stem cells (imMSCs) on the NB. In this study, primary bone marrow mesenchymal stem cells (BM-MSCs) were transfected into immortalized upregulated SDF-1-engineered BM-MSCs (imMSCs/eSDF-1+) or immortalized normal SDF-1-engineered BM-MSCs (imMSCs/eSDF-1−). NB rats induced by bilateral pelvic nerve (PN) transection were treated with imMSCs/eSDF-1+, imMSCs/eSDF-1−, or sham. After a 4-week treatment, the bladder function was assessed by cystometry and voiding pattern analysis. The PN and bladder tissues were evaluated via immunostaining and western blotting analysis. We found that imMSCs/eSDF-1+ expressed higher levels of SDF-1 in vitro and in vivo. The treatment of imMSCs/eSDF-1+ improved NB and evidently stimulated the recovery of bladder wall in NB rats. The recovery of injured nerve was more effective in the NB+imMSCs/eSDF-1+ group than in other groups. High SDF-1 expression improved the levels of vascular endothelial growth factor and basic fibroblast growth factor. Apoptosis was decreased after imMSCs injection, and was detected rarely in the NB+imMSCs/eSDF-1+ group. Injection of imMSCs boosted the expression of neuronal nitric oxide synthase, p-AKT, and p-ERK in the NB+imMSCs/eSDF-1+ group than in other groups. Our findings demonstrated that overexpression of SDF-1 induced additional MSC homing to the injured tissue, which improved the NB by accelerating the restoration of injured nerve in a rat model.

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