Medical Internal Radiation Dose Schema Research Articles

68Ga-Citrate PET of Healthy Men: Whole-Body Biodistribution Kinetics and Radiation Dose Estimates.

68Ga-citrate has one of the simplest chemical structures of all 68Ga-radiopharmaceuticals, and its clinical use is justified by the proven medical applications using its isotope-labeled compound 67Ga-citrate. To support broader application of 68Ga-citrate in medical diagnosis, further research is needed to gain clinical data from healthy volunteers. In this work, we studied the biodistribution of 68Ga-citrate and subsequent radiation exposure from it in healthy men. Methods: 68Ga-citrate was prepared with an acetone-based radiolabeling procedure compliant with good manufacturing practices. Six healthy men (age 41 ± 12 y, mean ± SD) underwent sequential whole-body PET/CT scans after an injection of 204 ± 8 MBq of 68Ga-citrate. Serial arterialized venous blood samples were collected during PET imaging, and the radioactivity concentration was measured with a γ-counter. Urinary voids were collected and measured. The MIRD bladder-voiding model with a 3.5-h voiding interval was used. A model using a 70-kg adult man and the MIRD schema was used to estimate absorbed doses in target organs and effective doses. Calculations were performed using OLINDA/EXM software, version 2.0. Results: Radioactivity clearance from the blood was slow, and relatively high radioactivity concentrations were observed over the whole of the 3-h measuring period. Although radioactivity excretion via urine was rather slow (biologic half-time, 69 ± 24 h), the highest decay-corrected concentrations in urinary bladder contents were measured at the 90- and 180-min time points. Moderate concentrations were also seen in kidneys, liver, and spleen. The source organs showing the largest residence times were muscle, liver, lung, and heart contents. The heart wall received the highest absorbed dose, 0.077 ± 0.008 mSv/MBq. The mean effective dose (International Commission on Radiological Protection publication 103) was 0.021 ± 0.001 mSv/MBq. Conclusion: PET imaging with 68Ga-citrate is associated with modest radiation exposure. A 200-MBq injection of 68Ga-citrate results in an effective radiation dose of 4.2 mSv, which is in the same range as other 68Ga-labeled tracers. This suggests the feasibility of clinical studies using 68Ga-citrate imaging in humans and the possibility of performing multiple scans in the same subjects across the course of a year.

Prospective evaluation of organ-specific dose and lesional doses following therapeutic [177Lu]Lu-EDTMP administration in patients with multiple skeletal metastases and its correlation with clinical hematological toxicity.

In patients with multiple skeletal metastases, accurate estimation of absorbed doses to radiosensitive bone marrow in bone-directed systemic radionuclide therapies (RNT) is critically important from clinical dose determination standpoint. The primary aim of the present study was to estimate the radiation absorbed doses of therapeutic [177Lu]Lu-EDTMP to bone marrow by two methods viz. Medical Internal Radiation Dose (MIRD) schema and using OLINDA software and correlate with hematological toxicity. A total of 15 patients diagnosed to have multiple painful skeletal metastases being treated with [177Lu]Lu-EDTMP for palliation of pain, were enrolled for this prospective study. For all patients, urine was collected immediately after infusion of [177Lu]Lu-EDTMP up to 24 h post-administration and cumulative activity excreted from body via urine was calculated. For dosimetry, patients underwent post-administration whole-body scintigraphy at five-time points: 0.5 (pre-void), 2, 24, 48 and 120 h (post-void). From the time-activity curves generated by drawing regions of interest (ROIs) on the images, number of disintegrations was determined. Absorbed doses for organs and bone lesions were calculated using OLINDA 2.2.0 software. For bone marrow dose estimates, in addition to OLINDA 2.2.0 software, MIRD schema was also adopted. Hematological profile was monitored in all patients during the treatment and post-treatment follow-up (estimating complete blood counts, every 15 d for 3 months after therapy). The mean ± standard deviation activity of [177Lu]Lu-EDTMP administered per patient per cycle was 2.08 ± 0.45 GBq. The results demonstrated higher uptake of [177Lu]Lu-EDTMP in bone metastases compared to normal bones. Within 2 and 24 h of administration of [177Lu]Lu-EDTMP, [177Lu]Lu activity excreted from the body was 24 ± 9% and 39 ± 14%, respectively. The mean absorbed organ doses (mean ± SD) in Gy/GBq were as follows: osteogenic cells 3.15 ± 1.85, bone marrow 0.57 ± 0.31, kidneys 0.08 ± 0.05, urinary bladder 0.32 ± 0.04, and bone lesions 2.91 ± 1.88. Strong correlation was found between (a) MIRD schema and OLINDA 2.2.0 software method for estimation of bone marrow doses (r = 0.96; P = <0.0001) and (b) Bone marrow absorbed dose and hematological toxicity (r = 0.81, P = 0.0027). Radiation absorbed doses to the bone marrow and skeletal metastatic lesions, following therapeutic [177Lu]Lu-EDTMP were estimated using a convenient and non-invasive quantitative imaging method. The estimated bone marrow absorbed dose, either by MIRD schema or the OLINDA 2.2.0 software method, demonstrated strong correlation. Strong correlation was also observed between bone marrow absorbed dose and hematological toxicity.

Preclinical voxel-based dosimetry through GATE Monte Carlo simulation using PET/CT imaging of mice

Internal dosimetry is of critical importance to obtain an accurate absorbed dose-response relationship during preclinical molecular imaging and targeted radionuclide therapy (TRT). Conventionally, absorbed dose calculations have been performed using organ-level dosimetry based on the Medical Internal Radiation Dose (MIRD) schema. However, recent research has focused on developing more accurate voxel-level calculation methods. Geant4 application for emission tomography (GATE) Monte Carlo (MC) is a simulation toolkit gaining attention in voxel-based dosimetry. In this study, we used PET/CT images of real mice to estimate the absorbed doses in sensitive organs at voxel-level to evaluate the suitability of GATE MC simulation for preclinical dosimetry. Thirteen normal C57BL/6 mice (male, body weight: 27.71 ± 4.25 g) were used to acquire dynamic positron emission tomography/computed tomography (PET/CT) images after IV injection of 18F-FDG. GATE MC toolkit was applied to estimate the absorbed doses in various organs of mice at voxel-level using CT and PET images as voxelized phantom and voxelized source, respectively. In addition, mean absorbed dose at organ-level was calculated using MIRD schema for comparison purposes. The differences in the respective absorbed doses (mGy MBq−1) between GATE MC and MIRD schema for brain, heart wall, liver, lungs, stomach wall, spleen, kidneys, and bladder wall were 1.36, 12.3, −22.4, −11.2, −16.9, −2.87, −4.29, and 3.71%, respectively. Considering that the PET/CT data of real mice were used for GATE simulation, the absorbed doses estimated in this study are mouse-specific. Therefore, the GATE-based Monte Carlo is likely to allow for more accurate internal dosimetry calculations. This method can be used in TRT for personalized dosimetry because it considers patient-specific heterogeneous tissue compositions and activity distributions.

Voxel-Based Dosimetry of Iron Oxide Nanoparticle-Conjugated 177Lu-Labeled Folic Acid Using SPECT/CT Imaging of Mice.

Several radiolabeled folic acid conjugates have been developed for targeted imaging and therapy. However, the therapeutic concept with radiolabeled folate conjugates has not yet been applied to clinical applications owing to the high renal absorbed dose. The effectiveness of targeted radionuclide therapy (TRT) depends primarily on the absorbed dose rate and on the total absorbed dose delivered to the tumor and to normal tissue. Owing to various limitations associated with organ level dosimetry, voxel-based dosimetry has become essential for the assessment of a more accurateabsorbed dose during TRT. In this study, we synthesized iron oxide nanoparticle (IONP)-conjugated radiolabeled folate (177Lu-IONP-Folate) and performed voxel-based dosimetry using SPECT/CT images of normal mice through direct Geant4 application for emission tomography (GATE) Monte Carlo (MC) simulation. We also prepared 177Lu-Folate and 177Lu-IONPs for the comparison of absorbed doses with that of 177Lu-IONP-Folate. In addition, we calculated the mean absorbed dose at the organ-level using the medical internal radiation dose (MIRD) schema. The radioactivities of all three radiotracers were mainly accumulated in the liver and kidneys immediately after injection. For the kidneys, the voxel-based absorbed doses obtained with 177Lu-IONP-Folate, 177Lu-Folate, and 177Lu-IONPs were 1.01 ± 0.17, 2.46 ± 0.50, and 0.52 ± 0.08 Gy/MBq, respectively. The renal absorbed dose decreased significantly (∼half) when 177Lu-IONP-Folate was used compared with when the 177Lu-Folate only was used. The mean absorbed dose values obtained at organ-level using the MIRD schema were comparable to voxel-based absorbed doses estimated with GATE MC. The voxel-based absorbed dose values obtained in this study of individualized activity show that the renal absorbed dose could be reduced to almost half with 177Lu-IONP-Folate. Therefore, 177Lu-IONP-Folate could be clinically applicable in the TRT of folate receptor-positive cancers in a personalized manner when using the voxel-based dosimetry method.

Patient-specific dosimetry in radionuclide therapy

This study presents an attempt to compare individualised palliative treatment absorbed doses, by planar images data and Monte Carlo simulation, in two in vivo treatment cases, one of bone metastases and the other of liver lesions. Medical Internal Radiation Dose schema was employed to estimate the absorbed doses. Radiopharmaceutical volume distributions and absorbed doses in the lesions as well as in critical organs were also calculated by Monte Carlo simulation. Individualised planar data calculations remain the method of choice in internal dosimetry in nuclear medicine, but with the disadvantage of attenuation and scatter corrections lack and organ overlay. The overall error is about 7 % for planar data calculations compared with that using Monte Carlo simulation. Patient-specific three-dimensional dosimetric calculations using single-photon emission computed tomography with a parallel computed tomography study is proposed as an accurate internal dosimetry with the additional use of dose-volume histograms, which express dose distributions in cases with obvious inhomogeneity.

Open-label, dose confirmation and dosimetry study of Interstitial 131I-chTNT-1/B MAb for the treatment of recurrent glioblastoma multiforme (GBM)

2072 Background: 131I-chTNT-1/B MAb (Cotara [C]) is a radioiodinated chimeric monoclonal antibody specific for DNA and histone H1 complex, which becomes exposed in the necrotic areas of gliomas. This is the first report on biodistribution and dosimetry of C for treatment of recurrent glioma. In a prior phase I trial with a single catheter, C was infused over ∼25 hrs using convection enhanced delivery (CED). This current trial assesses the use of 2 interstitial catheters to deliver C via CED. Methods: Patients with recurrent GBM and tumor volume of 5–60 cc are eligible. Patients receive 3 mCi of C for imaging and dosimetry followed 2–4 weeks later with a therapy dose. Cohorts of 3–6 patients will be enrolled to receive a therapy dose of 1.5, 2.0 or 2.5 mCi/cc. Biodistribution and dosimetry of C is determined using 5 sequential whole body images and counting 9 blood samples. Uptake and clearance of C in tissues were quantified and radiation doses were determined based on Medical Internal Radiation Dose schema. Results: Three patients received an imaging dose and then a therapy dose at 1.5 mCi/cc, both infused over ∼25 hrs with 2 interstitial catheters. The administered therapeutic radiation dose ranged from 17- 74 mCi and no dose limiting toxicities (DLT) were observed. From images acquired immediately and up to 168 hours post infusion, Cotara was concentrated only in tumor. Minimal uptake of Cotara could be faintly visualized only in stomach, heart, and thyroid. The peak uptake ranged from 1.1–3.3 %ID for stomach, 0.4–1.2 %ID for heart, 0.05–0.26 %ID for thyroid, 0.0009–0.0017 %ID/mL for blood, and 30–55.7 %ID for tumor. Radiation doses ranged 1.8–3.3 cGy/mCi for stomach, 0.9–1.6 cGy/mCi for heart, 0.7–4.4 cGy/mCi for thyroid, 0.9–1.6 cGy/mCi for contralateral healthy brain, 0.64–1.1 cGy/mCi for marrow from radioactivity in blood, and 179–598 cGy/mCi for tumor. Mean tumor-to-body dose ratio was 551 and ranged 223–732. Conclusions: CED administered C specifically localized only in tumor with minimal systemic radiation exposure. No DLTs were observed at the 1.5 mCi/cc dose level. These clinical and biodistribution/dosimetry findings are encouraging and support further dose escalation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Peregrine Pharmaceuticals Peregrine, Inc Peregrine, Inc

The application of polymer gel dosimeters to dosimetry for targeted radionuclide therapy

There is a lack of standardized methodology to perform dose calculations for targeted radionuclide therapy and at present no method exists to objectively evaluate the various approaches employed. The aim of the work described here was to investigate the practicality and accuracy of calibrating polymer gel dosimeters such that dose measurements resulting from complex activity distributions can be verified. Twelve vials of the polymer gel dosimeter, ‘MAGIC’, were uniformly mixed with varying concentrations of P-32 such that absorbed doses ranged from 0 to 30 Gy after a period of 360 h before being imaged on a magnetic resonance scanner. In addition, nine vials were prepared and irradiated using an external 6 MV x-ray beam. Magnetic resonance transverse relaxation time, T2, maps were obtained using a multi-echo spin echo sequence and converted to R2 maps (where T2 = 1/R2). Absorbed doses for P-32 irradiated gel were calculated according to the medical internal radiation dose schema using EGSnrc Monte Carlo simulations. Here the energy deposited in cylinders representing the irradiated vials was scored. A relationship between dose and R2 was determined. Effects from oxygen contamination were present in the internally irradiated vials. An increase in O2 sensitivity over those gels irradiated externally was thought to be a result of the longer irradiation period. However, below the region of contamination dose response appeared homogenous. Due do a drop-off of dose at the periphery of the internally irradiated vials, magnetic resonance ringing artefacts were observed. The ringing did not greatly affect the accuracy of calibration, which was comparable for both methods. The largest errors in calculated dose originated from the initial activity measurements, and were approximately 10%. Measured R2 values ranged from 5–35 s−1 with an average standard deviation of 1%. A clear relationship between R2 and dose was observed, with up to 40% increased sensitivity for internally irradiated gels. Curve fits to the calibration data followed a single exponential function. The correlation coefficients for internally and externally irradiated gels were 0.991 and 0.985, respectively. With the ability to accurately calibrate internally dosed polymer gels, this technology shows promise as a means to evaluate dosimetry methods, particularly in cases of non-uniform uptake of a radionuclide.

Internal dosimetry for systemic radiation therapy

The key to effective use of the medical internal radiation dose (MIRD) schema in radioimmunotherapy (RIT) is to understand how it works and what the essential data input requirements are. The fundamental data are acquired from medical imaging. Image interpretation involves (1) collecting data to determine the source-organ activities, (2) plotting the source-organ time-activity curves, (3) integrating the time-activity curves for an estimate of the residence time, and (4) applying the residence time values (for each important source organ) within the MIRD schema to calculate the tissue absorbed dose to target organs and tumors of interest. This article reviews methods for calculating internal dose. It also describes methods for selecting sampling times, integrating the area under the data curves, and customizing a dose assessment for a patient who does not resemble the MIRD phantom. A sample dose assessment is given, together with common mistakes to avoid. Three approaches to red marrow dosimetry are described. With the increased use of RIT agents for cancer treatment, a solid understanding of internal dose methods is essential for treatment planning and follow-up evaluations.

The AAPM/RSNA physics tutorial for residents: internal radiation dosimetry: principles and applications.

Internal dose calculations in nuclear medicine normally use the techniques, equations, and resources provided by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. The MIRD schema uses a unique set of symbols and quantities to calculate the absorbed dose of radiation in any target organ per radioactive decay in any source organ. The calculations involve the energy emitted per radioactive decay, the fraction of the emitted energy that is absorbed in various target organs, the masses of these organs, and both the physical decay and biologic clearance of the injected radioactive material. Standardized mathematical models (phantoms) of the human body and standardized biokinetic models are also used. A computer program, MIRDose, calculates dose tables per unit administered activity of various radiopharmaceuticals. Special care must be taken when nuclear medicine procedures involve pregnant or lactating patients. New methodologies are becoming available to calculate doses to individual patients.