Medical Internal Radiation Dosimetry Method Research Articles

Biodistribution and radiation dosimetry in cancer patients of the ascorbic acid analogue 6-Deoxy-6-[18F] fluoro-L-ascorbic acid PET imaging: first-in-human study.

Clinical studies on the use of ascorbic acid (AA) have become a hot spot in cancer research. There remains an unmet need to assess AA utilization in normal tissues and tumors. 6-Deoxy-6-[18F]fluoro-L-ascorbic acid ([18F]DFA) displayed distinctive tumor localization and similar distribution as AA in mice. In this study, to evaluate the distribution, tumor detecting ability and radiation dosimetry of [18F]DFA in humans, we performed the first-in-human PET imaging study. Six patients with a variety of cancers underwent whole-body PET/CT scans after injection of 313-634MBq of [18F]DFA. Five sequential dynamic emission scans in each patient were acquired at 5-60min. Regions of interest (ROI) were delineated along the edge of the source-organ and tumor on the transverse PET slice. Tumor-to-background ratio (TBR) was obtained using the tumor SUVmax to background SUVmean. Organ residence times were calculated via time-activity curves, and human absorbed doses were estimated from organ residence time using the medical internal radiation dosimetry method. [18F]DFA was well tolerated in all subjects without serious adverse event. The high uptake was found in the liver, adrenal glands, kidneys, choroid plexus, and pituitary gland. [18F]DFA accumulated in tumor rapidly and the TBR increased over time. The average SUVmax of [18F]DFA in tumor lesions was 6.94 ± 3.92 (range 1.62-22.85, median 5.94). The organs with the highest absorbed doses were the liver, spleen, adrenal glands, and kidneys. The mean effective dose was estimated to be 1.68 ± 0.36 E-02mSv/MBq. [18F]DFA is safe to be used in humans. It showed a similar distribution pattern as AA, and displayed high uptake and retention in tumors with appropriate kinetics. [18F]DFA might be a promising radiopharmaceutical in identifying tumors with high affinity for SVCT2 and monitoring AA distribution in both normal tissues and tumors. Chinese Clinical Trial Registry; Registered Number: ChiCTR2200057842 (registered 19 March 2022).

Evaluation of the physical and biological dosimetry methods in iodine-131-treated patients

The aim of the study was to compare physical and biological dosimetry methods in iodine-131 (I-131)-receiving patients. The present study comprised of 47 patients (mean age: 47.9 ± 15.8 years), treated with I-131. Group I consisted of 17 patients with hyperthyroidism and mean administered activity of this group was 432.9 ± 111 MBq. There were 15 follow-up patients of differentiated thyroid cancer (DTC) in Group II with mean administered activity of 185 ± 22.2 MBq, who were administered scanning dose of I-131. Group III comprised of 15 patients with DTC, ablated with high-dose of I-131, and this group's mean administered activity was 4347.5 ± 695.6 MBq. The whole-body absorbed doses were calculated in all patients both with the Medical Internal Radiation Dosimetry (MIRD) method using MIRDOSE3 software and cytokinesis-block micronucleus (MN) assay-based MN analysis and were compared. The whole-body absorbed dose, calculated by MIRD method, showed very good correlation with the administered I-131 activity (r = 0.89, P < 0.001), but it was moderate in the MN method (r = 0.52, P < 0.01). Absorbed dose estimations with MIRD method were 49.2 ± 20.8 mGy in Group I, 6.5 ± 1.6 mGy in Group II, and 154.3 ± 47.8 mGy in Group III; the differences were statistically significant (P < 0.001), as expected. Pre- and posttreatment MN frequencies differed significantly in all groups (P < 0.05). The whole-body absorbed doses, based on MN method, were 68.2 ± 17.5, 46.0 ± 11.4, and 90.5 ± 26.9 mGy in Groups I–III, respectively. The difference was significant between Group II and Group III (P < 0.01). The mean absorbed dose was 74.6 ± 27.9 mGy with MN versus 68.0 ± 67.1 mGy in MIRD method (P = 0.087) in the entire study population and the correlation was moderate (r = 0.73, P < 0.001). The whole-body absorbed doses, estimated by MN method, showed moderate correlation with administered radioiodine activities in low radioiodine doses and had significantly different and fluctuating values as compared to MIRD method in patients treated with I-131.

Evaluasi Akurasi Aktivitas Tc-99m pada Single Organ dan All Organ Menggunakan Kamera Gamma Mediso Anyscan S Dual Head dan Fantom Antropomorfik

In term of nuclear medical, Radiopharmaceuticals with Tc - 99m radioisotope for kidney examination inserted into the body will emit gamma radiation that can be detected by a gamma camera. Gamma camera will display the distribution of radioisotopes in the patient's body and measure examined organ function in the form of image. A committee in nuclear medical developed Medical Internal Radiation Dosimetry (MIRD) method, the standard method on the way calculating activities in organ by image quantification. Differences in the activity of Tc-99m were measured by a dose calibrator with detected activity of organs to determine the accuracy of activity measurement. These results indicated that detected activity in the organ, calculated by the method MIRD, were smaller than the calibrator measurement result. The differences percentage in the activity of a single organ (counting each organ), involving all organs (enumeration simultaneously including kidney, bladder, heart and liver), has value <20% that indicate the reliability of MIRD method to use in internal dosimetry.

Human Biodistribution and Radiation Dosimetry of S-11C-Methyl-L-Cysteine Using Whole-Body PET.

S-C-Methyl-L-cysteine (C-MCYS) is a recently developed amino acid PET tracer for tumor imaging. The present study estimated human radiation absorbed dose of C-MCYS in healthy volunteers based on whole-body PET imaging. Five sequential whole-body PET scans were performed on 6 healthy volunteers after injection of C-MCYS. Each scan contained of approximately 7 to 10 bed positions, and total scan time of each volunteer was approximately 70 to 85 minutes. Regions of interest were drawn on PET images of source organs. Residence times of 13 source organs for men and 14 source organs for women were calculated from the organ-specific time-activity curves. Absorbed dose estimates were performed from organ residence time by using the medical internal radiation dosimetry method. All volunteers showed initial high uptake in liver, heart, kidneys, pancreas, spleen, and uterus (only women), and followed by rapid clearance. There was very little activity residual in most of the organs except for the liver at the last emission scan time (approximately 75 minutes). The liver was the dose-limiting critical organ with the highest radiation-absorbed dose (1.01E-02 ± 2.64E-03 mGy/MBq), followed by the heart (9.09E-03 ± 1.40E-03 mGy/MBq), and the kidneys (7.12E-03 ± 9.44E-04 mGy/MBq). The effective dose to the whole body was 4.03E-03 ± 1.65E-04 mSv/MBq. A routine injection of 555 MBq (15 mCi) of C-MCYS would lead to an estimated effective dose of 2.24 ± 0.092 mSv. The potential radiation risks associated with C-MCYS PET imaging are within accepted limits. C-MCYS is a safe amino acid PET tracer for tumor imaging and can be used in further clinical studies.

Biodistribution and estimation of radiation-absorbed doses in humans for 13N-ammonia PET.

To evaluate the biodistribution of radiation-absorbed doses of (13)N-ammonia in healthy people. Five healthy human subjects underwent whole-body PET and CT scans after injection of 555-740 MBq of (13)N-ammonia. Five serial dynamic emission scans in each healthy volunteer were acquired. Regions of interest were drawn on the CT image and transferred to the corresponding transverse PET slice. Estimates of the radiation-absorbed doses were calculated using the medical internal radiation dosimetry method. The highest concentrations of (13)N-ammonia were found in the heart and liver, followed by pancreas, brain, spleen and stomach. The highest absorbed organ doses were to the heart wall (7.14E-03 ± 3.63E-03 mGy/MBq) and kidneys (6.02E-03 ± 3.53E-03 mGy/MBq). The effective dose (ED) was 6.58E-03 ± 1.23E-03 mSv/MBq. With these new estimates for (13)N-ammonia dosimetry, the results for Chinese people were not appreciably different from those of the previous study performed with old devices. As one of the most important myocardial perfusion PET tracers, the whole-body (13)N-ammonia PET appears to be safe for humans, yielding a relatively modest radiation burden that would allow multiple PET studies on the same subject per year.

Evaluation of factors affecting tumor response and survival in patients with primary and metastatic liver cancer treated with microspheres.

Radioembolization with the yttrium-90 (Y-90) microspheres is being used increasingly more often in the treatment of patients with primary or metastatic liver cancer. Although technetium-99m macroaggregated albumin (Tc-99m MAA) scintigraphy performed following diagnostic angiography has an important role in predicting the effectiveness of treatment and in dose estimation, the number of studies using quantitative assessment of Tc-99m MAA scintigraphy is limited in this field. In the present study, the aim was to assess whether a tumor dose is required to obtain objective tumor response and to check whether this threshold value is predictive in terms of tumor response, survival, and liver toxicity by using Tc-99m MAA single-photon emission computed tomography (SPECT) images. Overall, 54 patients (20 women and 34 men; median age: 60 years) who underwent Y-90 Resin (SIR-Spheres) and Glass (TheraSphere) microsphere treatment with a diagnosis of unresectable liver cancer between August 2010 and April 2013 were included in the study. The mean doses to normal liver and tumor were estimated for each patient using Tc-99m MAA SPECT images and the medical internal radiation dosimetry method. The responses were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) and European Organisation for Research and Treatment of Cancer (EORTC) criteria. Kaplan-Meier survival curves and univariate Cox regression analysis were used in survival analysis. The relationship between treatment response and other parameters included was assessed using logistic regression analysis. The variables with a P value less than 0.01 in univariate analysis were assessed with multivariate analysis. Fifty-four Y-90 microsphere treatments (eight by using a Y-90 glass microsphere and 46 by using a Y-90 resin microsphere) were performed. In the multivariate analysis, the only parameter related to response was tumor dose (P<0.01). With a tumor dose of 280 Gy or higher, objective tumor response was observed in 59 and 77% of the patients according to RECIST and EORTC criteria, respectively, and the tumor control rate was found to be 95% according to both criteria. In addition, it was found that only tumor dose was correlated with progression-free survival (PFS) (P<0.001) and overall survival (OS) (P=0.018). When the tumor dose was 280 Gy or higher, median PFS increased from 2 to 10.7 months (P<0.001), whereas median OS increased from 9 to 17.6 months (P=0.018). However, reversible ≥ G2 liver toxicity was observed in 3.7% (2/54) of the patients within 3 months after radioembolization with a median normal liver dose of 40 Gy (10-102 Gy). There was reversible ≥ G3 liver toxicity in 3.7% (2/54) of patients, but no G4 liver toxicity was observed. Clinical radiation hepatitis and treatment-induced liver failure were not observed in any of these patients. Tc-99m MAA SPECT has a predictive value in terms of response to radioembolization, PFS, and OS. Dosimetry based on Tc-99m MAA SPECT images can be used in the selection of patients and, in particular, to adaptation of treatment plan in selected patients.

Comparison of the Absorbed Dose for (99m)Tc-Diethylenetriaminepentaacetic Acid and (99m)Tc-Ethylenedicysteine Radiopharmaceuticals using Medical Internal Radiation Dosimetry.

The aim of this study was the investigation of absorbed dose to the kidneys, spleen, and liver during technetium-99 m ethylene dicysteine and technetium-99 m diethylenetriaminepentaacetic acid ((99m)Tc-EC and (99m)Tc-DTPA) kidney scan. Patients who had been prepared for the kidney scan, were divided into two groups (Groups 1 and 2). The first group (Group 1) and the second group (Group 2) received intravenous injection of (99m)Tc-EC and (99m)Tc-DTP, respectively. A certain amount of radiopharmaceuticals was injected into each patient and was immediately imaged with dual-head gamma camera to calculate the activity through the conjugated view method. Then, the doses of kidney, liver, and spleen were measured using medical internal radiation dosimetry method. Finally, absorbed dose of these organs was compared. Based on these different results (P < 0.05), organs absorbed dose was significantly less with radiopharmaceutical (99m)Tc-EC as compared with (99m)Tc-DTPA.

The determination of patient dose from 18F-FDG PET/CT examination

The use of positron emission tomography/computed tomography (PET/CT) system has heightened the need for medical diagnosis. However, the patient dose is increasing in comparison to whole-body PET/CT dose. The aim of this study is to determine the patient effective dose in 35 oncology Thai patients with the age range of 28-60 y from PET scan using [fluorine-18]-fluoro-2-deoxy-D-glucose and from CT scan. Cumulated activity and residence time of various organs were calculated from time-activity curves by using S-value based on the body mass. Mean organ absorbed dose and the effective dose from CT scan were calculated using the Medical Internal Radiation Dosimetry method and Monte Carlo simulation, respectively. The average whole-body effective doses from PET and CT were 4.40 + or - 0.61 and 14.45 + or - 2.82 mSv, respectively, resulting in the total patient dose of 18.85 mSv. This can be used as the reference dose in Thai patients.

Estimation of internal absorbed dose of L-[methyl-11C]methionine using whole-body positron emission tomography.

L-[Methyl-11C]-methionine (11C-methionine) is proposed as a useful radiotracer for tumour diagnosis. Human biodistribution data of cumulated activities and absorbed doses estimated by the MIRD (medical internal radiation dosimetry) method for 11C-methionine are not available in the literature. In this study we measured the organ activity for 11C-methionine by using whole-body positron emission tomography (PET) and estimated the absorbed doses to 25 organs by the MIRD method. Whole-body dynamic PET scans were performed on five normal volunteers to measure the time course of the organ activity concentration (activity/volume) after intravenous administration of 11C-methionine. Cumulated activities of the ten source organs were calculated from the time-activity curves, obtained from the dynamic PET data. Absorbed dose estimates were performed by the MIRD method for the Caucasian reference man and for the Japanese reference man. The organs which received the highest absorbed doses for the Caucasian reference man were found to be the bladder wall (2.7x10(-2) mGy/MBq), the pancreas (1.9x10(-2) mGy/ MBq), the liver (1.8x10(-2) mGy/MBq) and the kidney (1.1x10(-2) mGy/MBq). The effective doses for the Caucasian reference man and the Japanese reference man were calculated as 5.2x10(-3) and 5.0x10(-3) mSv/MBq, respectively.

Estimation of absorbed dose for 2-[F-18]fluoro-2-deoxy- d - glucose using whole-body positron emission tomography and magnetic resonance imaging

The purpose of this study was to measure the cumulated activity and absorbed dose in organs after intravenous administration of 2-[F-18]fluoro-2-deoxy-D-glucose (18F-FDG) using whole-body positron emission tomography (PET) and magnetic resonance imaging (MRI). Whole-body dynamic emission scans for 18F-FDG were performed in six normal volunteers after transmission scans. The total activity of a source organ was obtained from the activity concentration of the organ measured by whole-body PET and the volume of that organ measured by whole-body T1-weighted MRI. The cumulated activity of each source organ was calculated from the time-activity curve. Absorbed doses to the individuals were estimated by the MIRD (medical internal radiation dosimetry) method using S-values adjusted to the individuals. Another calculation of cumulated activities and absorbed doses was performed using the organ volumes from the MIRD phantom and the "Japanese reference man" to investigate the discrepancy of actual individual results against the phantom results. The cumulated activities of 18 source organs were calculated, and absorbed doses of 27 target organs estimated. Among the target organs, bladder wall, brain and kidney received the highest doses for the above three sets of organ volumes. Using measured individual organ volumes, the average absorbed doses for those organs were found to be 3.1x10(-1), 3.7x10(-2) and 2.8x10(-2) mGy/MBq, respectively. The mean effective doses in this study for individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were the same, i.e. 2.9x10(-2) mSv/MBq, while for the Japanese reference man of 60 kg the effective dose was 2.1x10(-2) mSv/MBq. The results for measured organ volumes derived from MRI were comparable to those obtained for organ volumes from the MIRD phantom. Although this study considered 18F-FDG, combined use of whole-body PET and MRI might be quite effective for improving the accuracy of estimations of the cumulated activity and absorbed dose of positron-labelled radiopharmaceuticals.