Monitoring the biodistribution of radiolabeled therapeutics in mice.

Radiopharmaceutical therapy is a rapidly growing field for the treatment of cancer due to its high specificity and ability to target individual affected cells. A key component of the pre-clinical development of a new therapeutic radiopharmaceutical is the determination of its time-dependent distribution in tumors, normal tissues, and the whole body in mouse tumor models. Here, we provide an overview of the available instrumentation for the novice in radiation measurement. We also detail the methodology for assessing distribution and kinetics of a radiopharmaceutical and calculating radiation absorbed dose in mice using a gamma counter or a PET or SPECT camera.

Clinical perspectives on dosimetry in molecular radiotherapy.

Molecular radiotherapy is the use of systemically administered unsealed radioactive sources to treat cancer. Theragnostics is the term used to describe paired radiopharmaceuticals localising to a specific target, one optimised for imaging, the other for therapy. For many decades, molecular radiotherapy has developed empirically. Standard administered activity schedules have been used without the prior estimation of the resulting tumour radiation absorbed dose by theragnostic imaging, or its subsequent measurement by serial scanning. This pragmatic approach has benefited many patients, however others who should have benefited have failed to do so as the radiation absorbed dose in the tumour was suboptimal. The accurate prediction and measurement of tumour and organ at risk radiation absorbed doses allows treatment to be personalised, and offers the prospect of improved clinical outcomes. To deliver this for all molecular radiotherapy patients would require not only a significant financial investment in equipment and skilled personnel, but also a change in attitude of those who believe that simple - or simplistic - schedules are easier to deliver, and that accurate dosimetry is too much trouble. Further clinical studies are required to demonstrate beyond doubt that the advantages of individualised treatment planning outweigh the inconvenience, and that the expense is justified by enhanced results.

Monte Carlo simulation for assessing absorbed dose effects of low-dose ß-radiation (90Sr/90Y) on cytotoxicity and apoptotic death in K562 cells.

Objective: Most studies suggest that dose-specific radiation regimens are essential for optimal induction of cancer cell response. This study focused on determining ß-radiation-absorbed dose (rad) effects on the cell viability, cytotoxicity, hypersensitivity, and cell death of K562 cells using experimental methods and Monte Carlo simulation (MCS). Materials and Methods: The K562 cells were cultured and irradiated with ß-particles emitted from a strontium source in vitro, with the estimated daily activity of 1.238 µCi. The treated cells were radiated at least three times every day for 3 consecutive days. The cell viability and apoptosis were investigated in treated cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, DNA electrophoresis, Hoechst dye, and inverted microscope. The average absorbed doses were obtained by MCS (MCNPX code). To verify simulation and experimental results, we used a Geiger-Muller counter and estimated a scaling factor. Results: The cytotoxic effects and cell death were induced in the treated groups via rad in a time-dependent manner. The highest apoptotic and cytotoxic effects were observed in cells after irradiation with ß-particles for 120 min per day in 3 consecutive days. rads were determined using MCNPX code and cell survival rates were significantly reduced during irradiation periods. No significant hyper-radiosensitivity was found based on experimental and theoretical results. Conclusion: Despite the difficult calculation of the rad in the target cells and the scant information in this field, fortunately we have achieved significant theoretical data consistent with the experimental results. Our findings also introduced MCS as a better choice for evaluating of rad effects under different cellular conditions with high accuracy.

A Systematic Review and Meta-Analysis of the Relationship Between the Radiation Absorbed Dose to the Thyroid and Response in Patients Treated with Radioiodine for Graves' Disease.

Background: Patients with Graves' disease are commonly treated with radioiodine. There remains controversy over whether the aim of treatment should be to achieve euthyroidism or hypothyroidism, and whether treatments should be administered with standard levels of radioactivity or personalized according to the radiation absorbed doses delivered to the thyroid. The aim of this review was to investigate whether a relationship exists between radiation absorbed dose and treatment outcome. Methods: A systematic review and meta-analysis of all reports published before February 13, 2020, were performed using PubMed, Web of Science, OVID MEDLINE, and Embase. Proportion of patients achieving nonhyperthyroid status was the primary outcome. Secondary outcomes were proportion of patients who were specifically euthyroid or hypothyroid. A random-effects meta-analysis of proportions was performed for primary and secondary outcomes, and the impact of the radiation absorbed dose on treatment outcome was assessed through meta-regression. The study is registered with PROSPERO (CRD42020175010). Results: A total of 1122 studies were identified of which 15, comprising 2303 Graves' disease patients, were eligible for the meta-analysis. A strong association was found between radiation absorbed dose and nonhyperthyroid and hypothyroid outcomes (odds ratio [OR] = 1.11 [95% confidence interval {CI} 1.08-1.14] and OR = 1.09 [CI 1.06-1.12] per 10 Gy increase). Higher rates of euthyroid outcome were found for radiation absorbed doses within the range 120-180 Gy when compared with outside this range (n = 1172, OR = 2.50 [CI 1.17-5.35], p = 0.018). A maximum euthyroid response of 38% was identified at a radiation absorbed dose of 128 Gy. Conclusions: The presented radiation absorbed dose-response relationships can facilitate personalized treatment planning for radioiodine treatment of patients with Graves' disease. Further studies are required to determine how patient-specific covariates can inform personalized treatments.

Data on biodistribution and dose calculation of 99mTechnetium -Dimercaptosuccinic acid in pediatric patients using a hybrid planar/single emission computed tomography method.

The Biodistribution and absorbed dose data from the administration of radiopharmaceuticals are necessary to analyze the risk-benefit of the procedure. It has particular significance in children, as their metabolism is very different from adults. 99mTc-DMSA scintigraphy is the golden standard imaging technique for the assessment of renal involvement in febrile urinary tract infection and renal sequels. However, 99mTc-DMSA biodistribution data for children are scarce and usually outdated which have been obtained by older methods. In this data article, we analysed the biodistribution of 99mTc-DMSA in 12 pediatric patients using planar/SPECT method. In addition, the radiation absorbed doses were calculated by MIRDOSE software.

Determination and Comparison of Radiation Absorbed dose to the Blood, by Applying Different Techniques, for Patients, Suffering from Differentiated Thyroid Cancer.

BACKGROUND: Radiation absorbed dose to the red bone marrow, in the therapy of differentiated thyroid carcinoma (DTC) with 131I (radioiodine), cannot be measured directly. The absorbed dose to the blood seems to be a good first- order approximation of the radiation absorbed dose to the hematopoietic system and a better means to quantify exposure from therapy than the total amount of activity administered. OBJECTIVE: The aim of this research was to determine the radiation absorbed dose to the blood, for patients suffering from differentiated thyroid cancer. MATERIALS AND METHODS: Twenty seven patients, 22 women and 5 men, suffering from DTC were enrolled in this study. We applied four formulas and we compared between the estimated values of absorbed dose that were obtained by three formulas and those that obtained by fourth (standard one). RESULTS: All the values of absorbed dose that obtained by one of the techniques were regularly highly estimated, even though they have an excellent correlation (99%) with the standard value. CONCLUSIONS: Highly overestimated or highly underestimated results that can be obtained by certain method or technique are not desirable, because they tend to exaggerate, by increasing or decreasing, the radiation protection procedures. CONVERSION RADIATION UNITS: To convert the values of absorbed dose from S.I unit (mGy/MBq) to traditional unit (rad/mCi), we can simply multiply the values that expressed in S.I units by a factor of 3.7, and we don't need to apply complicated formulas, which were applied by other researches.

Radiation absorbed dose estimates for 18F-BPA PET.

Background Boron neutron capture therapy (BNCT) is a molecular radiation therapy approach based on the 10B (n, α) 7Li nuclear reaction in cancer cells. In BNCT, delivery of 10B in the form of 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is important. The PET tracer 4-borono-2-18F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. Purpose To determine the biodistribution and dosimetric parameters in 18F-BPA PET/CT studies. Material and Methods Human biokinetic data were obtained during clinical 18F-BPA PET studies between February and June 2015 at one institution. Nine consecutive patients were studied prospectively. The internal radiation dose was calculated on the basis of radioactivity data from blood, urine, and normal tissue of the heart, liver, spleen, kidney, and other parts of the body at each time point using OLINDA/EXM1.1 program. We compared our calculations with published 18F-FDG data. Results Adult patients (3 men, 3 women; age range, 28-68 years) had significantly smaller absorbed doses than pediatric patients (3 patients; age range, 5-12 years) ( P = 0.003). The mean effective dose was 57% lower in adult patients compared with pediatric patients. Mean effective doses for 18F-BPA were 25% lower than those for 18F-FDG presented in International Commission of Radiation Protection (ICRP) publication 106. Conclusion We found significant differences in organ absorbed doses for 18F-BPA against those for 18F-FDG presented in ICRP publication 106. Mean effective doses for 18F-BPA were smaller than those for 18F-FDG in the publication by 0.5-38% (mean difference, 25%).

Biodistribution and Radiation Dosimetry of 11C-Nicotine from Whole-Body PET Imaging in Humans.

This study assessed the in vivo distribution of 11C-nicotine and the absorbed radiation dose from whole-body 11C-nicotine PET imaging of 11 healthy (5 male and 6 female) subjects. Methods: After an initial CT attenuation scan, 11C-nicotine was administered via intravenous injection. A dynamic PET scan was acquired for 90 s with the brain in the field of view, followed by a series of 13 whole-body PET scans acquired over a 90-min period. Regions of interest were drawn over organs visible in the reconstructed PET images. Time-activity curves were generated, and the residence times were calculated. The absorbed radiation dose for the whole body was calculated by entering the residence time in OLINDA/EXM 1.0 software to model the equivalent organ dose and the effective dose for a 70-kg man. Results: The mean residence times for 11C-nicotine in the liver, red marrow, brain, and lungs were 0.048 ± 0.010, 0.031 ± 0.005, 0.021 ± 0.004, and 0.020 ± 0.005 h, respectively. The mean effective dose for 11C-nicotine was 5.44 ± 0.67 µSv/MBq. The organs receiving the highest absorbed dose from the 11C-nicotine injection were the urinary bladder wall (14.68 ± 8.70 µSv/MBq), kidneys (9.56 ± 2.46 µSv/MBq), liver (8.94 ± 1.67 µSv/MBq), and spleen (9.49 ± 3.89 µSv/MBq). The renal and hepatobiliary systems were the major clearance and excretion routes for radioactivity. Conclusion: The estimated radiation dose from 11C-nicotine administration is relatively modest and would allow for multiple PET examinations on the same subject.

An update on radiation absorbed dose to patients from diagnostic nuclear medicine procedures in Tehran: A study on four academic centers.

PURPOSE: Use of radiopharmaceuticals for diagnostic nuclear medicine procedures is one of the main sources of radiation exposure. We performed this study with respect to the rapid growth in nuclear medicine in Iran and lack of updated statistics. MATERIALS AND METHODS: The data were obtained for all active Nuclear Medicine Centers affiliated to Shahid Beheshti University of Medical Sciences during 2009 and 2010. RESULTS: The most frequently performed procedures were bone (30.16%), cardiac (28.96%), renal (17.97%), and thyroid (7.93%) scans. There was a significant decrease in the number of thyroid scintigraphies with (131)I and (99m)Tc-sulfur colloid liver/spleen scans and tremendous increase in the frequencies of cardiac and bone scintigraphies compared to one decade ago. CONCLUSION: Compared to previous studies, there were striking changes in trends of diagnostic nuclear medicine procedures in Tehran. This field is still evolving in the country, and this trend will further change with the introduction of positron emission tomography scanners in future.

Data on biodistribution and radiation absorbed dose profile of a novel (64)Cu-labeled high affinity cell-specific peptide for positron emission tomography imaging of tumor vasculature.

New peptide-based diagnostic and therapeutic approaches hold promise for highly selective targeting of cancer leading to more precise and effective diagnostic and therapeutic modalities. An important feature of these approaches is to reach the tumor tissue while limiting or minimizing the dose to normal organs. In this context, efforts to design and engineer materials with optimal in vivo targeting and clearance properties are important. This Data In Brief article reports on biodistribution and radiation absorbed dose profile of a novel high affinity radiopeptide specific for bone marrow-derived tumor vasculature. Background information on the design, preparation, and in vivo characterization of this peptide-based targeted radiodiagnostic is described in the article "Synthesis and comparative evaluation of novel 64Cu-labeled high affinity cell-specific peptides for positron emission tomography of tumor vasculature" (Merrill et al., 2016) [1]. Here we report biodistribution measurements in mice and calculate the radiation absorbed doses to normal organs using a modified Medical Internal Radiation Dosimetry (MIRD) methodology that accounts for physical and geometric factors and cross-organ beta doses.

Synthesis and comparative evaluation of novel (64)Cu-labeled high affinity cell-specific peptides for positron emission tomography imaging of tumor vasculature.

Tumor angiogenesis, the formation of new tumor blood supply, has been recognized as a hallmark of cancer and represents an important target for clinical management of various angiogenesis-dependent solid tumors. Previously, by screening a bacteriophage peptide library we have discovered the FHT-peptide sequence that binds specifically to bone marrow-derived tumor vasculature with high affinity. Here in an effort to determine the potential of the FHT-peptide for in vivo positron emission tomography (PET) imaging of aggressive tumor vasculature we studied four FHT-derivatives: NOTA-FHT, NOTA-(FHT)2, NOTA-PEG-FHT, and NOTA-PEG-(FHT)2. These peptide analogs were synthesized, labeled with the PET radionuclide (64)Cu, and characterized side-by-side with small animal PET and computed tomography imaging (microPET/CT) at 1 h, 4 h, and 24 h post injection in a subcutaneous Lewis lung carcinoma (LLC) tumor model. Because of its excellent in vivo kinetic properties and high tumor-to-background ratio, the (64)Cu-NOTA-FHT radiopeptide was selected for more detailed evaluation. Blocking studies with excess of unlabeled peptide showed specific and peptide mediated (64)Cu-NOTA-FHT tumor uptake. Biodistribution experiments in the same tumor model confirmed microPET/CT imaging results. Human radiation absorbed dose extrapolated from rodent biodistribution of (64)Cu-NOTA-FHT revealed favorable dosimetry profile. The findings from this investigation warrant further development of (64)Cu-NOTA-FHT as a potential targeted diagnostic radiopharmaceutical for PET imaging of aggressive tumor vasculature.

Absorbed radiation doses to staff after implementation of a radiopharmacy clean room.

UNLABELLED: In response to U.S. Pharmacopeia general chapter <797> standards, a clean room was constructed for our in-house radiopharmacy. Previously, most patient doses were prepared as needed just before injection. Currently, to minimize repeated entries into the clean room, most patient doses are prepared in batches; that is, early morning and noontime preparation of doses to be injected at various times throughout the morning and the afternoon, respectively. Because these patient doses may be prepared well before injection time, radioactive decay necessitates higher amounts of radioactivity to be handled for patient dose preparation. Hence, absorbed radiation doses to staff, all of whom rotate into the radiopharmacy clean room in addition to their regular patient-related activities, were retrospectively evaluated. METHODS: Monthly dosimetry reports for body (chest badge) and extremities (finger ring) were retrospectively reviewed for each staff member for 12 mo before and 12 mo after implementation of the radiopharmacy clean room. Monthly data were evaluated for average and SD, and 12-mo groups were evaluated using a paired t test. Data for the second 12-mo period were also normalized to the same number of patient doses to account for an increase in procedure volume and were reevaluated. RESULTS: Before the radiopharmacy clean room had been implemented, average monthly absorbed radiation doses to body and extremities were 23 ± 15 mrem (0.23 ± 0.15 mSv) and 93 ± 59 mrem (0.93 ± 0.59 mSv), respectively. After the clean room had been implemented, average monthly absorbed radiation doses increased to 32 ± 16 mrem (0.32 ± 0.16 mSv) (P < 0.001) and 121 ± 89 mrem (1.21 ± 0.89 mSv) (P = 0.0015), respectively. When normalized for procedure volume, average monthly absorbed radiation doses after implementation of the clean room were still higher, at 29 ± 15 mrem (0.29 ± 0.15 mSv) (P = 0.001) and 110 ± 80 mrem (1.10 ± 0.80 mSv) (P = 0.039), respectively. CONCLUSION: After implementation of a radiopharmacy clean room, absorbed radiation doses to body and extremities increased by 26% and 18%, respectively, even after normalizing for procedure volume. Because absorbed radiation doses from other activities, such as patient dose administration and patient imaging, are assumed to remain relatively constant, these increases in absorbed radiation doses to staff are attributed to changes in work flow after implementation of the radiopharmacy clean room.

A Randomized Controlled Trial about the Levels of Radiation Exposure Depends on the Use of Collimation C-arm Fluoroscopic-guided Medial Branch Block.

BACKGROUND: C-arm fluoroscope has been widely used to promote more effective pain management; however, unwanted radiation exposure for operators is inevitable. We prospectively investigated the differences in radiation exposure related to collimation in Medial Branch Block (MBB). METHODS: This study was a randomized controlled trial of 62 MBBs at L3, 4 and 5. After the patient was laid in the prone position on the operating table, MBB was conducted and only AP projections of the fluoroscope were used. Based on a concealed random number table, MBB was performed with (collimation group) and without (control group) collimation. The data on the patient's age, height, gender, laterality (right/left), radiation absorbed dose (RAD), exposure time, distance from the center of the field to the operator, and effective dose (ED) at the side of the table and at the operator's chest were collected. The brightness of the fluoroscopic image was evaluated with histogram in Photoshop. RESULTS: There were no significant differences in age, height, weight, male to female ratio, laterality, time, distance and brightness of fluoroscopic image. The area of the fluoroscopic image with collimation was 67% of the conventional image. The RAD (29.9 ± 13.0, P = 0.001) and the ED at the left chest of the operators (0.53 ± 0.71, P = 0.042) and beside the table (5.69 ± 4.6, P = 0.025) in collimation group were lower than that of the control group (44.6 ± 19.0, 0.97 ± 0.92, and 9.53 ± 8.16), resepectively. CONCLUSIONS: Collimation reduced radiation exposure and maintained the image quality. Therefore, the proper use of collimation will be beneficial to both patients and operators.

A Randomized Controlled Trial about the Levels of Radiation Exposure Depends on the Use of Collimation C-arm Fluoroscopic-guided Medial Branch Block

BACKGROUND: C-arm fluoroscope has been widely used to promote more effective pain management; however, unwanted radiation exposure for operators is inevitable. We prospectively investigated the differences in radiation exposure related to collimation in Medial Branch Block (MBB). METHODS: This study was a randomized controlled trial of 62 MBBs at L3, 4 and 5. After the patient was laid in the prone position on the operating table, MBB was conducted and only AP projections of the fluoroscope were used. Based on a concealed random number table, MBB was performed with (collimation group) and without (control group) collimation. The data on the patient's age, height, gender, laterality (right/left), radiation absorbed dose (RAD), exposure time, distance from the center of the field to the operator, and effective dose (ED) at the side of the table and at the operator's chest were collected. The brightness of the fluoroscopic image was evaluated with histogram in Photoshop. RESULTS: There were no significant differences in age, height, weight, male to female ratio, laterality, time, distance and brightness of fluoroscopic image. The area of the fluoroscopic image with collimation was 67% of the conventional image. The RAD (29.9 +/- 13.0, P = 0.001) and the ED at the left chest of the operators (0.53 +/- 0.71, P = 0.042) and beside the table (5.69 +/- 4.6, P = 0.025) in collimation group were lower than that of the control group (44.6 +/- 19.0, 0.97 +/- 0.92, and 9.53 +/- 8.16), resepectively. CONCLUSIONS: Collimation reduced radiation exposure and maintained the image quality. Therefore, the proper use of collimation will be beneficial to both patients and operators.

Study on radiation dose based on chrominance / 第二军医大学学报

Objective: To set up a new measurement method for radiation absorbed dose by using chrominance technology. Methods: The changes of trichromatic values were measured using color analysis technique after different concentrations of alphaurine A aqueous solutions (500 mg/L, 250 mg/L, and 150 mg/L) were irradiated with 1.5-13.5 kGy doses of γ-rays at room temperature. Immediately after irradiation, the trichromatic color testing device was used to determine the trichromatic color changes of the samples for further statistical processing, analysis, and mapping. Repeated measurements were obtained with the test samples. The samples was stored at room temperature of summer for two weeks and the above protocol was repeated. Paired t-test was used for statistical analysis. Results: The trichromatic red-green-blue color underwent evident changes with the changes of reagent concentrations and absorbed doses. There was a gradual increment of absorption value (80-360) of the red color with the increment of absorbed dose in 500 mg/L group; meanwhile, there was a decrement of absorption value (580-250) of blue color with the increment of absorbed dose, which showed that the changing trend of the red color and blue color was on contrary. Compared with the red and blue, the absorption value of green color underwent a slighter change(270-320) with the increment of absorbed doses. Despite a similar color change trend in all the experimental groups, the solution concentration and the radiation dose were the main factor for ideal trichromatic data. The change of color in the solution of lower concentration was greater within a smaller range of absorption dose. Temperature had little influence on the measuring results after the irradiated samples were kept for two weeks at the room temperature in the summer (P>0.05). Conclusion: Ionizing radiation-induced color change combined with chrominance technique may provide a new convenient method for studying radiation absorbed dose.

Study on radiation dose based on chrominance / 第二军医大学学报

0.05).Conclusion:Ionizing radiation-induced color change combined with chrominance technique may provide a new convenient method for studying radiation absorbed dose.