Internal Dosimetry Research Articles

Dosimetry of nuclear medicine therapies: current controversies and impact on treatment optimization.

Nuclear medicine therapeutic procedures have considerably expanded over the last few years, and their number is expected to grow exponentially in the future. Internal dosimetry has significantly developed as well, but has not yet been uniformly accepted as a valuable tool for prediction of therapeutic efficacy and toxicity. In this paper, we briefly summarize some of the arguments about the implementation of internal dosimetry in clinical practice. In addition, we provide a few examples of radionuclide anticancer therapies for which internal dosimetry demonstrated a significant impact on treatment optimization and patient outcome.

Dosimetry for Radiopharmaceutical Therapy: Current Practices and Commercial Resources.

With the ongoing dramatic growth of radiopharmaceutical therapy, research and development in internal radiation dosimetry continue to advance both at academic medical centers and in industry. The basic paradigm for patient-specific dosimetry includes administration of a pretreatment tracer activity of the therapeutic radiopharmaceutical; measurement of its time-dependent biodistribution; definition of the pertinent anatomy; integration of the measured time-activity data to derive source-region time-integrated activities; calculation of the tumor, organ-at-risk, and/or whole-body absorbed doses; and prescription of the therapeutic administered activity. This paper provides an overview of the state of the art of patient-specific dosimetry for radiopharmaceutical therapy, including current methods and commercially available software and other resources.

OD154 - Internal dosimetry Monte Carlo study of TARE treatments: a comparison between GATE and GAMOS focused on lung dosimetry and background correction

OD154 - Internal dosimetry Monte Carlo study of TARE treatments: a comparison between GATE and GAMOS focused on lung dosimetry and background correction

Toward a Patient-Specific Traceable Quantification of SPECT/CT-Based Radiopharmaceutical Distributions.

Quantitative SPECT/CT imaging is currently the state of the art for peritherapeutic monitoring of radiopharmaceutical distributions. Because of poor resolution, however, the verification of SPECT/CT-based activity distributions is of particular importance. Because of the lack of a ground truth in patient measurements, phantoms are commonly used as a substitute for clinical validation of quantitative SPECT/CT. Because of the time-consuming and erroneous preparation of multicompartment phantoms, such as for the kidney, the usually very complex internal activity distributions are typically replaced by 1- or 2-compartment models. To provide a simplified solution for generating inhomogeneous activity distributions, this work presents a methodology for designing single-compartment phantoms that mimic inhomogeneous spatial activity distributions by using internal filling structures of different volume fractions. Methods: A series of phantoms with different filling structures was designed, 3-dimensionally printed, and measured. After assessing the feasibility of the presented approach in a simple geometry, a set of three patient-specific kidney phantoms was designed on the basis of the contrast-enhanced CT scan of a patient with metastatic castration-resistant prostate cancer. Internal gyroid structures of different wall thicknesses were used in the renal medulla and cortex to reproduce the inhomogeneous activity distribution observed in a peritherapeutic SPECT/CT acquisition 24 h after injection of 177Lu-labeled prostate-specific membrane antigen (apparent activity concentration ratios of 1:1, 1:3.5, and 1:7.5). After 3-dimensional printing, SPECT/CT experiments were performed and the results were compared with the patient data for different reconstruction settings (iterations, subsets, and postfiltering). Results: Good agreement was found between phantom designs and fabricated phantoms (based on high-resolution CT). No internal filling structures were visible in any of the SPECT images, indicating a sufficiently small feature size. Although good visual and quantitative agreement was achieved for certain combinations of filling structure and reconstruction, a histogram analysis indicated an even more complex activity distribution in the patient than represented by the two compartments assumed in our model. Conclusion: The proposed methodology provides patient-specific phantoms mimicking inhomogeneous activity distributions while using a single stock solution, thus simplifying the filling process and reducing uncertainties in the activity determination. This method enables an unprecedented possibility for patient-specific evaluation of radiopharmaceutical uptake, reducing uncertainties in internal dosimetry and individualized treatments.

GATE Monte Carlo dosimetry in 90Y TARE planning: influence of simulation parameters and image resampling on dosimetric accuracy and optimization of computational times

Direct Monte Carlo (MC) simulation is considered the gold standard approach for internal dosimetry in nuclear medicine, and it is increasingly used in planning Trans-Arterial Radio-Embolization (TARE) of HepatoCellular Carcinoma (HCC) {and hepatic metastases}. However its computational times, longer with respect to other simplified approaches, constitute a limiting factor, especially when dealing with {large size and finely discretized voxelized volumes}. Aim of this work was the investigation of the influence of cuts on the production of secondary particles and of input CT images resamplings on dosimetric accuracy and computational time in patient-specific voxel-level MC simulations of 90 Y-labelled glass microspheres TARE treatment, to find optimal combinations of settings for speeding up such simulations. GATE GEANT4 interface was used to perform simulations employing CT and 99m Tc SPECT as input data, examining multiple CT resolutions (via CT resamplings characterized by voxel volume factors 2, 8, and 64 with respect to native one, and a CT resampling with SPECT resolution) and production cuts (0.01 mm, 0.05 mm, 0.1 mm, 0.5 mm and some more, specific for each resampling). Increasing cut length and reducing CT resolution produces an early rapid decrease followed by a late slow decrease of simulation time as a function of this two parameters. A reduction up to 30% with respect to reference simulation time, while preserving acceptable dosimetric accuracy, was obtained. The best combination of settings among the examined ones resulted the choice of CT resampling with 8 times the native voxel volume and of 0.1-0.5 mm cut, ensuring dosimetric agreement within 1% in liver-related VOIs, while reducing simulation time to 45%.

Implementation of a triage monitoring program for internal exposure to short-lived radionuclides in Israel—challenges and recommendations

Monitoring internal exposure to short-lived radionuclides is challenging, due to the frequent measurements required. ISO Standard 16 637 and the Swiss Personal Dosimetry Ordinance describe a screening measurement (triage monitoring) conducted in the workplace to identify workers suspected of internal exposure. Based on a previous study that examined the feasibility of using several commonly found radiation monitors in Israel in a triage monitoring program, we conducted a pilot study towards the implementation of triage monitoring in nuclear medicine facilities in Israel. The pilot study was conducted while considering the current Israeli regulations and local safety culture. We implemented the triage monitoring program in three nuclear medicine facilities in Israel, with a total of 55 monitored workers. The pilot study consisted of two stages: a short-term stage conducted in the largest manufacture of radiopharmaceuticals in Israel and a long-term stage in two nuclear medicine departments in Israel. During the first stage of the study, participants were asked to conduct a daily measurement at the end of the workday and send a urine sample to the national internal dosimetry laboratory. The second stage lasted 5 months in a major hospital and 18 months in a regional hospital. The workers were asked to perform the measurement at the end of the shift and send a urine sample if a defined threshold had been crossed. The mean participation rate in the long-term stage (>70%) indicates that implementation of the triage monitoring program could be successful in Israel. Based on the findings of the study, practical recommendations are listed: suitable monitoring devices, allocating a monitoring location, time of measurement, training of the workers, record keeping and coordination with a certified dosimetry laboratory. The pilot study recommendations were submitted to the Israel Institute for Occupational Safety and Hygiene at the Ministry of Labor, Social Affairs and Social Services.

An integrated exposure and pharmacokinetic modeling framework for assessing population-scale risks of phthalates and their substitutes.

To effectively incorporate in vitro-in silico-based methods into the regulation of consumer product safety, a quantitative connection between product phthalate concentrations and in vitro bioactivity data must be established for the general population. We developed, evaluated, and demonstrated a modeling framework that integrates exposure and pharmacokinetic models to convert product phthalate concentrations into population-scale risks for phthalates and their substitutes. A probabilistic exposure model was developed to generate the distribution of multi-route exposures based on product phthalate concentrations, chemical properties, and human activities. Pharmacokinetic models were developed to simulate population toxicokinetics using Bayesian analysis via the Markov chain Monte Carlo method. Both exposure and pharmacokinetic models demonstrated good predictive capability when compared with worldwide studies. The distributions of exposures and pharmacokinetics were integrated to predict the population distributions of internal dosimetry. The predicted distributions showed reasonable agreement with the U.S. biomonitoring surveys of urinary metabolites. The "source-to-outcome" local sensitivity analysis revealed that food contact materials had the greatest impact on body burden for di(2-ethylhexyl) adipate (DEHA), di-2-ethylhexyl phthalate (DEHP), di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH), and di(2-propylheptyl) phthalate (DPHP), whereas the body burden of diethyl phthalate (DEP) was most sensitive to the concentration in personal care products. The upper bounds of predicted plasma concentrations showed no overlap with ToxCast in vitro bioactivity values. Compared with the in vitro-to-in vivo extrapolation (IVIVE) approach, the integrated modeling framework has significant advantages in mapping product phthalate concentrations to multi-route risks, and thus is of great significance for regulatory use with a relatively low input requirement. Further integration with new approach methodologies will facilitate these in vitro-in silico-based risk assessments for a broad range of products containing an equally broad range of chemicals.

InterDosi Monte Carlo simulations of photon and electron specific absorbed fractions in a voxel-based crab phantom.

InterDosi is a new in-house Monte Carlo code that aims at facilitating the use of the Geant4 toolkit for internal dosimetry using voxel-based phantoms. In the present work the dosimetric capabilities of this code are assessed by calculating self-irradiation specific absorbed fractions (SI-SAFs) in a voxel-based crab phantom. Recent standard human organ compositions and densities taken from ICRP Publication 110 have been used for material specifications of the four organs of a crab, namely, the heart, hepatopancreas, gills, and gonads, whereas the material assigned to the crab shell has been modeled based on literature values. The SI-SAFs were calculated for mono-energetic photons of energies between 10 and 4000keV, and for mono-energetic electrons of energies between 100 and 4000keV. The statistical errors corresponding to the calculated SI-SAFs were all less than 0.01%. The results obtained demonstrate that the simulated masses and volumes of the crab organs are in good agreement with those presented in the literature. In addition, the dosimetric results show that the calculated SI-SAFs are generally consistent with those reported in the literature, with some moderate differences due to differences in material specification. It is concluded that the InterDosi code can be successfully employed in internal dose estimations in small organisms, and it is suggested that material specifications specifically relating to crab tissues should be developed to provide more precise SI-SAFs.

Dr. Edith H. Quimby: A pioneering medical physicist and educator with outstanding contributions in radiation dosimetry

Dr. Edith H. Quimby: A pioneering medical physicist and educator with outstanding contributions in radiation dosimetry

Monte Carlo calculation of organ dose coefficients for internal dosimetry: Results of an international intercomparison exercise

EURADOS Working Group 6 has organized an intercomparison exercise on the use of the ICRP Reference Computational Phantoms with radiation transport codes. This paper summarizes the results of a specific task from the intercomparison exercise modelling internal radiation sources. The quantities to be calculated were absorbed fractions and specific absorbed fractions for monoenergetic photon and electron sources as well as S-values for two radionuclides in four source organs. Twelve participants from eleven countries participated in this specific task using the Monte Carlo radiation transport codes FLUKA, Geant4, the MCNP code family, PenEasy, TRIPOLI-4 and VMC. Although some participants provided initial solutions in good agreement with the master solution evaluated by the organizers, differences of factors or even orders of magnitude were also found. Following feedback from the organizer, most participants submitted revised solutions that were mostly in better agreement with the master solution, although this was not always the case. Some initial and revised results are discussed in detail in this paper, and the reasons of mistakes are described as far as they were revealed by the participants. A full account of all results is presented in specific annexes as supplemental material.

Monoclonal antibody based radiopharmaceuticals for imaging and therapy

The concept of personalized medicine has been steadily growing for the past decades. Monoclonal antibodies (mAbs) are undoubtedly playing an important role in the transition away from conventional medical practice to a more tailored approach to deliver the best therapy with the highest safety margin to a specific patient. In certain instances, mAbs and antibody drug conjugates (ADCs) may represent the preferred therapeutic option for several types of cancers due to their high specificity and affinity to the antigen. Monoclonal antibodies can be labeled with specific radionuclides well-suited for PET (Positron Emission Tomography) or gamma camera scintigraphy. The use of radiolabeled mAbs allows the interrogation of specific biomarkers and assessment of tumor heterogeneity in vivo by a single diagnostic imaging scan that includes the whole-body in the field-of-view. Moreover, the same mAb can then be radiolabeled with an analogous radionuclide for the delivery of beta-minus radiation or alpha-particles as part of a radioimmunotherapy (RIT) approach. However, the path to develop, validate, and implement mAb-based radiopharmaceuticals from bench-to-bedside is complex due to the extensive pre-clinical experiments and toxicological studies required, and the necessity of labor-intensive clinical trials that often require multi-time-point imaging and blood draws for internal radiation dosimetry and pharmacokinetics. As more mAb-based radiopharmaceuticals have been developed and evaluated, the opportunities and limitations offered by mAbs have become better defined. Our aim with this manuscript is therefore to provide an overview of the recent advances in the development of mAb-based radiopharmaceuticals and their clinical applications in Oncology.

A SIMPLE AND NOVEL APPROACH TO STUDY KINETICS AND ESTIMATE RADIATION DOSES FROM INTERNALLY ADMINISTERED RADIOPHARMACEUTICALS USING AN EXTERNAL DOSE MEASUREMENT SYSTEM.

Various methods have been reported to study radiotracer kinetics and make internal dosimetry feasible in the routine clinical nuclear medicine practice. The aim of the present study was to quantify cumulative activity and organ doses using an indigenously designed and fabricated external dose measurement system. The measurement was demonstrated on patients undergoing whole-body (WB) 18F-FDG (Fluorine-18-fluorodeoxyglucose) direct positron emission tomography/computed tomography investigations. An external dose measurement system comprising of an ionisation chamber-survey meter and the movable focussing collimator was used to quantify the uptake of 18F-FDG in liver and brain. Cumulative activity and normalised cumulative activity in these organs were calculated. The results were validated by performing measurements on a phantom uniformly filled with known activity of 18F-FDG.The difference in the absorbed dose estimated with and without collimator was statistically significant (p<0.05). The external dose measurement technique is relatively novel, convenient and reliable for the assessment of internal absorbed dose of organs.

Perspectives on Internal Dosimetry for Optimized Radionuclide Therapy.

Abstract A balanced approach to radiopharmaceutical dosimetry involves personalized dosimetry. Planar quantitative imaging can be practical, reliable, and relatively cost-effective. Therapy dose optimization can be achieved for the individual patient using a straightforward tracer study to determine patient-specific biokinetics at three or more imaging time points for organs that assimilate the radiopharmaceutical. Two-dimensional quantitative imaging may be supported and calibrated using a 3D SPECT/CT measurement for the dose-limiting organ at a single time point. Organ volumes are needed from CT images. Measurements require special attention for consistency in camera-to-patient distancing, region-of-interest delineation, and attenuation correction, and operators need training and experience well beyond the requirements for standard nuclear medicine scintigraphy. As with external beam therapy, reimbursement codes are needed to support treatment-planning costs. Postinfusion tumor dosimetry can be important in overall evaluation of radionuclide therapy effectiveness. Clinicians and pharmaceutical companies should recognize the value of a balanced approach to personalized internal dosimetry for maximizing therapy benefit while minimizing toxicity. Prospective clinical trials should employ quantitative dosimetry with standardized methodologies to deliver predictive paradigms and establish the efficacy of new radioimmunotherapy products.

Exposure to an Environmental Mixture of Polycyclic Aromatic Hydrocarbons Induces Hepatic Cytochrome P450 Enzymes in Mice.

Cytochrome P450 enzymes (CYPs) play an important role in bioactivating or detoxifying polycyclic aromatic hydrocarbons (PAHs), common environmental contaminants. While it is widely accepted that exposure to PAHs induces CYPs, effectively increasing rates of xenobiotic metabolism, dose- and time-response patterns of CYP induction are not well-known. In order to better understand dose- and time-response relationships of individual CYPs following induction, we exposed B6129SF1/J mice to single or repeated doses (2-180 μmol/kg/d) of benzo[a]pyrene (BaP) or Supermix-10, a mixture of the top 10 most abundant PAHs found at the Portland Harbor Superfund Site. In hepatic microsomes from exposed mice, we measured amounts of active CYPs using activity-based protein profiling and total CYP expression using global proteomics. We observed rapid Cyp1a1 induction after 6 h at the lowest PAH exposures and broad induction of many CYPs after 3 daily PAH doses at 72 h following the first dose. Using samples displaying Cyp1a1 induction, we observed significantly higher metabolic affinity for BaP metabolism (Km reduced 3-fold), 3-fold higher intrinsic clearance, but no changes to the Vmax. Mice dosed with the highest PAH exposures exhibited 1.7-5-fold higher intrinsic clearance rates for BaP compared to controls and higher Vmax values indicating greater amounts of enzymes capable of metabolizing BaP. This study demonstrates exposure to PAHs found at superfund sites induces enzymes in dose- and time-dependent patterns in mice. Accounting for specific changes in enzyme profiles, relative rates of PAH bioactivation and detoxification, and resulting risk will help translate internal dosimetry of animal models to humans and improve risk assessments of PAHs at superfund sites.

The internal dosimetry user group position statement on molecular radiotherapy.

The Internal Dosimetry User Group (IDUG) is an independent, non-profit group of medical professionals dedicated to the promotion of dosimetry in molecular radiotherapy (www.IDUG.org.uk). The Ionising Radiation (Medical Exposure) Regulations 2017, IR(ME)R, stipulate a requirement for optimisation and verification of molecular radiotherapy treatments, ensuring doses to non-target organs are as low as reasonably practicable. For many molecular radiotherapy treatments currently undertaken within the UK, this requirement is not being fully met. The growth of this field is such that we risk digressing further from IR(ME)R compliance potentially delivering suboptimal therapies that are not in the best interest of our patients. For this purpose, IDUG proposes ten points of action to aid in the successful implementation of this legislation. We urge stakeholders to support these proposals and ensure national provision is sufficient to meet the criteria necessary for compliance, and for the future advancement of molecular radiotherapy within the UK.

Conventional Hepatic Volumetry May Lead to Inaccurate Segmental Yttrium-90 Radiation Dosimetry.

To compare radioembolization treatment zone volumes from mapping cone beam CT (CBCT) versus planning CT/MRI and to model their impact on dosimetry. Y90 cases were retrospectively identified in which intra-procedural CBCT angiograms were performed. Segmental and lobar treatment zone volumes were calculated with semi-automated contouring using Couinaud venous anatomy (planning CT/MRI) or tumor angiosome enhancement (CBCT). Differences were compared with a Wilcoxon signed-rank test. Treatment zone-specific differences in segmental volumes by volumetric method were also calculated and used to model differences indelivered dose using medical internal radiation dosimetry (MIRD) at 200 and 120Gy targets. Anatomic, pathologic, and technical factors likely affecting segmental volumes by volumetric method were evaluated. Forty segmental and 48 lobar CBCT angiograms and corresponding planning CT/MRI scans were included. Median Couinaud- and CBCT-derived segmental volumes were 281 and 243mL, respectively (p = 0.005). Differences between Couinaud and CBCT lobar volumes (right, left) were not significant (p = 0.24, p = 0.07). Couinaud overestimated segmental volumes in 28 cases by a median of 98mL (83%) and underestimated in 12 cases by median 69mL (20%). At a 200Gy dose target, Couinaud estimates produced median delivered doses of 367 and 160Gy in these 28 and 12 cases. At a 120Gy target, Couinaud produced doses of 220 and 96Gy. Proximal vs. distal microcatheter positioning, variant arterial anatomy, and tumor location on or near segmental watersheds were leading factors linked to volumetric differences. Use of CBCT-based volumetry may allow more accurate, personalized dosimetry for segmental Y90 radioembolization.

Analysis of absorbed dose in radioimmunotherapy with 177Lu-trastuzumab using two different imaging scenarios: a pilot study.

Internal organ dosimetry is an important procedure to demonstrate the reliable application of 177Lu-trastuzumab radioimmunotherapy for human epidermal growth factor receptor-positive metastatic breast cancers. We are reporting the first human dosimetry study for 177Lu-trastuzumab. Another objective of our study was to calculate and compare the absorbed doses for normal organs and tumor lesions in patients before radioimmunotherapy with 177Lu-trastuzumab using two different imaging scenarios. Eleven patients (48.27 ± 8.95 years) with a history of metastatic breast cancer were included in the study. Postadministration of 177Lu-trastuzumab (351.09 ± 23.89 MBq/2 mg), acquisition was performed using planar and hybrid imaging scenarios at 4, 24, 72 and 168 h. Single-photon emission computed tomography/computed tomography imaging was performed at 72 h postinjection. Acquired images were processed using Dosimetry Toolkit software for the estimation of normalized cumulated activity in organs and tumor lesions. OLINDA/EXM 2.0 software was used for absorbed dose calculation in both scenarios. Significant difference in normalized cumulated activity and the absorbed dose is noted between two imaging scenarios for the organs and tumor lesions (P < 0.05). Mean absorbed dose (mGy/MBq) estimated from heart, lungs, liver, spleen, kidney, adrenal, pancreas and colon using planar and hybrid scenarios were 0.81 ± 0.19 and 0.63 ± 0.17; 0.75 ± 0.13 and 0.32 ± 0.06; 1.26 ± 0.25 and 1.01 ± 0.17; 0.68 ± 0.22 and 0.53 ± 0.16; 0.91 ± 0.3 and 0.69 ± 0.24; 0.18 ± 0.04 and 0.11 ± 0.02; 0.25 ± 0.22 and 0.09 ± 0.02 and 0.75 ± 0.61 and 0.44 ± 0.28, respectively. On the basis of our dosimetric evaluation, we concluded that radioimmunotherapy with 177Lu-trastuzumab is well tolerated to be implemented in routine clinical practice against HER2 positive metastatic breast cancer. Liver is the main critical organ at risk. Hybrid scenario demonstrated significantly lower absorbed doses in organs and tumors compared to the multiplanar method.

Biodistribution and internal radiation dosimetry of a companion diagnostic radiopharmaceutical, [68Ga]PSMA-11, in subcutaneous prostate cancer xenograft model mice

[68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [68Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [68Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [68Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions.

Internal dosimetry in F-18 FDG PET examinations based on long-time-measured organ activities using total-body PET/CT: does it make any difference from a short-time measurement?

PurposeA 2-m axial field-of-view, total-body PET/CT scanner (uEXPLORER) has been recently developed to provide total-body coverage and ultra-high sensitivity, which together, enables opportunities for in vivo time-activity curve (TAC) measurement of all investigated organs simultaneously with high temporal resolution. This study aims at quantifying the cumulated activity and patient dose of 2-[F-18]fluoro-2-deoxy-D-glucose (F-18 FDG ) imaging by using delayed time-activity curves (TACs), measured out to 8-h post-injection, for different organs so that the comparison between quantifying approaches using short-time method (up to 75 min post-injection) or long-time method (up to 8 h post-injection) could be performed.MethodsOrgan TACs of 10 healthy volunteers were collected using total-body PET/CT in 4 periods after the intravenous injection of F-18 FDG. The 8-h post-injection TACs of 6 source organs were fitted using a spline method (based on Origin (version 8.1)). To compare with cumulated activity estimated from spline-fitted curves, the cumulated activity estimated from multi-exponential curve was also calculated. Exponential curve was fitted with shorter series of data consistent with clinical procedure and previous dosimetry works. An 8-h dynamic bladder wall dose model considering 2 voiding were employed to illustrate the differences in bladder wall dose caused by the different measurement durations. Organ absorbed doses were further estimated using Medical Internal Radiation Dose (MIRD) method and voxel phantoms.ResultsA short-time measurement could lead to significant bias in estimated cumulated activity for liver compared with long-time-measured spline fitted method, and the differences of cumulated activity were 18.38% on average. For the myocardium, the estimated cumulated activity difference was not statistically significant due to large variation in metabolism among individuals. The average residence time differences of brain, heart, kidney, liver, and lungs were 8.38%, 15.13%, 25.02%, 23.94%, and 16.50% between short-time and long-time methods. Regarding effective dose, the maximum differences of residence time between long-time-measured spline fitted curve and short-time-measured multi-exponential fitted curve was 9.93%. When using spline method, the bladder revealed the most difference in the effective dose among all the investigated organs with a bias up to 21.18%. The bladder wall dose calculated using a long-time dynamic model was 13.79% larger than the two-voiding dynamic model, and at least 50.17% lower than previous studies based on fixed bladder content volume.ConclusionsLong-time measurement of multi-organ TACs with high temporal resolution enabled by a total-body PET/CT demonstrated that the clinical procedure with 20 min PET scan at 1 h after injection could be used for retrospective dosimetry analysis in most organs. As the bladder content contributed the most to the effective dose, a long-time dynamic model was recommended for the bladder wall dose estimation.

Microspheres Used in Liver Radioembolization: From Conception to Clinical Effects.

Inert microspheres, labeled with several radionuclides, have been developed during the last two decades for the intra-arterial treatment of liver tumors, generally called Selective Intrahepatic radiotherapy (SIRT). The aim is to embolize microspheres into the hepatic capillaries, accessible through the hepatic artery, to deliver high levels of local radiation to primary (such as hepatocarcinoma, HCC) or secondary (metastases from several primary cancers, e.g., colorectal, melanoma, neuro-endocrine tumors) liver tumors. Several types of microspheres were designed as medical devices, using different vehicles (glass, resin, poly-lactic acid) and labeled with different radionuclides, 90Y and 166Ho. The relationship between the microspheres’ properties and the internal dosimetry parameters have been well studied over the last decade. This includes data derived from the clinics, but also computational data with various millimetric dosimetry and radiobiology models. The main purpose of this paper is to define the characteristics of these radiolabeled microspheres and explain their association with the microsphere distribution in the tissues and with the clinical efficacy and toxicity. This review focuses on avenues to follow in the future to optimize such particle therapy and benefit to patients.