Administered Activity Research Articles

National and local diagnostic reference levels for adult 18F-FDG and CT in Jordanian PET/CT: findings and implications in practice

This study aims to report the findings of Jordanian national diagnostic reference level (NDRL) survey for fluorodeoxyglucose (18F-FDG) and local diagnostic reference level (LDRL) of computed tomography (CT) used for attenuation correction and anatomical localisation (AC-AL); and AC and diagnostic CT (AC-DX) within the context of whole-body WB and half-body HB adult oncology PET/CT scanning. Two-structured questionnaires were prepared to gather the necessary information: dosimetry data, patient demographics, equipment specification, and acquisition protocols for identified 18F-FDG PET/CT procedures. The NDRL and achievable dose were reported based on the 75th and 50th percentiles for 18F-FDG administered activity (AA), respectively. The LDRL was reported based on the 50th percentile for (CTDIvol) and (DLP). Data from 562 patients from four Jordanian PET/CT centres were collected. The survey revealed that Jordanian NDRL for AA (303 MBq) was within the acceptable range compared to the published-peer NDRL data (240–590 MBq). However, the 18F-FDG AA varied across the participated PET/CT centres. The reported LDRL CTDIvol and DLP of CT used for (AC-AL) was 4.3 mGy and 459.3 mGy.cm for HB CT scan range, and 4.1 mGy and 659.9 mGy.cm for WB CT scans. The reported LDRL for CTDIvol and DLP for HB CT was higher when compared with the United Kingdom (3.2 mGy and 310 mGy.cm). Concurrently, in the context of WB CT, the reported values (i.e. CTDIvol and DLP) were also higher than both Kuwait (3.6 mGy and 659 mGy.cm) and Slovenia (3.6 mGy and 676 mGy.cm). The reported HB CT(AC-DX) was higher than Nordic, New Zealand and Swiss NDRLs and for WB (AC-DX) CT it was higher than Swiss NDRLs. This study reported the first Jordanian NDRL for 18F-FDG and LDRL for HB and WB CT associated with 18F-FDG PET/CT scans. This data is useful for Jordanian PET/CT centres to compare their LDRL to the suggested DRLs and utilise it in the process of optimising CT radiation doses.

Girth-based administered activity for pediatric 99m Tc-DMSA SPECT.

Pediatric molecular imaging requires a balance between administering an activity that will yield sufficient diagnostic image quality while maintaining patient radiation exposure at acceptable levels. In current clinical practice, this balance is arrived at by the current North American Consensus Guidelines in which patient weight is used to recommend the administered activity (AA). We have previously demonstrated that girth (waist circumference at the level of the kidneys) is better at equalizing image quality than patient weight for pediatric Tc-99m DMSA renal function imaging. However, the correlation between image quality (IQ), AA, and patient girth has not been rigorously and systematically developed. In this work, we generate a series of curves showing the tradeoff between AA and IQ as a function of patient girth, providing the data for standards bodies to develop the next generation of dosing guideline for pediatric DMSA SPECT. An anthropomorphic phantom series that included variations in age (5, 10, and 15 years), gender (M, F), local body morphometry (5, 10, 50, 90, and 95th girth percentiles), and kidney size (±15% standard size), was used to generate realistic SPECT projections. A fixed and clinically challenging defect-to-organ volume percentage (0.49% of renal cortex value) was used to model a focal defect with zero uptake (i.e., full local loss of renal function). Task-based IQ assessment methods were used to rigorously measure IQ in terms of renal perfusion defect detectability. This assessment was performed at multiple count levels (corresponding to various AAs) for groups of patients that had similar girths and defect sizes. Receiver-operating characteristics (ROC) analysis was applied; the area under the ROC curve (AUC) was used as a figure-of-merit for task performance. Curves showing the tradeoff between AUC and AA were generated for these groups of phantoms. Overall, the girth-based dosing method suggested different amounts of AA compared to weight-based dosing for the phantoms that had a relatively large body weight but a small girth or phantoms with relatively small bodyweight but large girth. Reductions of AA to 62.9% compared to weight-based dosing guidelines can potentially be realized while maintaining a baseline (AUC=0.80) IQ for certain 15-year-olds who have a relatively small girth and large defect size. Note that the task-based IQ results are heavily dependent on the simulated defect size for the defect detection task and the appropriate AUC value must be decided by the physicians for this diagnostic task. These results are based purely on simulation and are subject to future clinical validation. The study provides simulation-based IQ-AA data for a girth-based dosing method for pediatric renal SPECT, suggesting that patient waist circumference at the level of kidneys should be considered in selecting the AA needed to achieve an acceptable IQ. This data may be useful for standards bodies to develop girth-based dosing guidelines.

The establishment of national diagnostic reference levels for adult SPECT-CT in Saudi Arabia

This study aims to introduce national diagnostic reference levels (NDRLs) for adult hybrid single photon emission computed tomography (SPECT-CT) in nuclear medicine (NM) departments in the Kingdom of Saudi Arabia. The administered activity (AA) of radiopharmaceuticals, volume-weighted computed tomography dose index (CTDIvol) and dose length product (DLP) for ten hybrid SPECT/CT examinations were collected and analysed for one year. The median of AA, CTDIvol and DLP for each dose quantity was derived and the suggested national DRLs were determined based on the 75th percentile for all identified SPECT-CT examinations. A comparison of the defined adult NDRLs in Saudi Arabia with the published data of other countries was performed. Although there are no significant variations of the proposed NDRL of AA between countries, the proposed NDRLs of the integrated CT metrics exceed the published data in most procedures. NM departments are urged to consider optimisation for both image quality and radiation protection.

Impact of cyclic changes in pharmacokinetics and absorbed dose in pediatric neuroblastoma patients receiving [177Lu]Lu-DOTATATE

PurposeRecent reports personalizing the administered activity (AA) of each cycle of peptide receptor radionuclide therapy based on the predicted absorbed dose (AD) to the kidneys (dose-limiting organ) have been promising. Assuming identical renal pharmacokinetics for each cycle is pragmatic, however it may lead to over- or under-estimation of the optimal AA. Here, we investigate the influence that earlier cycles of [177Lu]Lu-DOTATATE had on the biokinetics and AD of subsequent cycles in a recent clinical trial that evaluated the safety and activity of [177Lu]Lu-DOTATATE in pediatric neuroblastoma (NBL). We investigated whether predictions based on an assumption of unchanging AD per unit AA (Gy/GBq) prove robust to cyclical changes in biokinetics.MethodsA simulation study, based on dosimetry data from six children with NBL who received four-cycles of [177Lu]Lu-DOTATATE in the LuDO trial (ISRCTN98918118), was performed to explore the effect of variable biokinetics on AD. In the LuDO trial, AA was adapted to the patient’s weight and SPECT/CT-based dosimetry was performed for the kidneys and tumour after each cycle. The largest tumour mass was selected for dosimetric analysis in each case.ResultsThe median tumour AD per cycle was found to decrease from 15.6 Gy (range 8.12–26.4) in cycle 1 to 11.4 Gy (range 9.67–28.8), 11.3 Gy (range 2.73–32.9) and 4.3 Gy (range 0.72–20.1) in cycles 2, 3 and 4, respectively. By the fourth cycle, the median of the ratios of the delivered AD (ADD) and the predicted (or “expected”) AD (ADE) (which was based on an assumption of stable biokinetics from the first cycle onwards) were 0.16 (range 0.02–0.92, p = 0.013) for the tumour and 1.08 (range 0.84–1.76, p > 0.05) for kidney. None of the patients had an objective response at 1 month follow up.ConclusionThis study demonstrates variability in Gy/GBq and tumour AD per cycle in children receiving four administrations of [177Lu]Lu-DOTATATE treatment for NBL. NBL is deemed a radiation sensitive tumour; therefore, dose-adaptive treatment planning schemes may be appropriate for some patients to compensate for decreasing tumour uptake as treatment progresses.Trial registration ISRCTN ISRCTN98918118. Registered 20 December 2013 (retrospectively registered).

ASSESSMENT OF PATIENT'S RADIATION EXPOSURES RESULTED FROM PET/CT 18F-FCH AND 68GA-PSMA PROCEDURES.

This study has sought to evaluate patient exposures during the course of particular diagnostic positron emission tomography and computed tomography (PET/CT) techniques. A total of 73 patients were examined using two types of radiopharmaceutical: 18F-fluorocholine (FCH, 48 patients) and 68Ga-prostate-specific membrane antigen (PSMA, 25 patients). The mean and range of administered activity (AA) in MBq, and effective dose (mSv) for FCH were 314.4±61.6 (462.5-216.8) and 5.9±1.2 (8.8-4.11), respectively. Quoted in the same set of units, the mean and range of AA and effective dose for 68Ga-PSMA were 179.3±92.3 (603.1-115.1) and 17.9±9.2 (60.3-11.5). Patient effective doses from 18F-FCH being a factor of two greater than the dose resulting from 68Ga-PSMA PET/CT procedures. CT accounts for some 84 and 23% for 18F-FCH and 68Ga-PSMA procedures, accordingly CT acquisition parameter optimization is recommended. Patient doses have been found to be slightly greater than previous studies.

Body morphometry appropriate computational phantoms for dose and risk optimization in pediatric renal imaging with Tc-99m DMSA and Tc-99m MAG3

Current guidelines for administered activity (AA) in pediatric nuclear medicine imaging studies are based on a 2016 harmonization of the 2010 North American Consensus guidelines and the 2007 European Association of Nuclear Medicine pediatric dosage card. These guidelines assign AA scaled to patient body mass, with further constraints on maximum and minimum values of radiopharmaceutical activity. These guidelines, however, are not formulated based upon a rigor-ous evaluation of diagnostic image quality. In a recent study of the renal cortex imaging agent 99mTc-DMSA (Li Y et al 2019), body mass-based dosing guidelines were shown to not give the same level of image quality for patients of differing body mass. Their data suggest that patient girth at the level of the kidneys may be a better morphometric parameter to consider when selecting AA for renal nuclear medicine imaging. The objective of the present work was thus to develop a dedicated series of computational phantoms to support image quality and organ dose studies in pediatric renal imaging using 99mTc-DMSA or 99mTc-MAG3. The final library consists of 50 male and female phantoms of ages 0 to 15 years, with percentile variations (5th to 95th) in waist circumference (WC) at each age. For each phantom, nominal values of kidney volume, length, and depth were incorporated into the phantom design. Organ absorbed doses, detriment-weighted doses, and stochastic risks were assessed using ICRP reference biokinetic models for both agents. In Monte Carlo radiation transport simulations, organ doses for these agents yielded detriment-weighted dose coefficients (mSv/MBq) that were in general larger than current ICRP values of the effective dose coefficients (age and WC-averaged ratios of eDW/e were 1.40 for the male phantoms and 1.49 for the female phantoms). Values of risk index (ratio of radiation-induced to natural background cancer incidence risk x 100) varied between 0.062 (newborns) to 0.108 (15-year-olds) for 99mTc-DMSA and between 0.026 (newborns) to 0.122 (15-year-olds) for 99mTc-MAG3. Using tallies of photon exit fluence as a rough surrogate for uniform image quality, our study demonstrated that through body region-of-interest optimization of AA, there is the potential for further dose and risk reductions of between factors of 1.5 to 3.0 beyond simple weight-based dosing guidance.

Effective Dose to Patients from SPECT and CT During Myocardial Perfusion Imaging.

Radiation dose to patients from imaging modalities is measured or calculated to assess the risk of the procedure and compare it with the benefits. Periodic review of image acquisition methods and the radiation dose used are an essential part of optimization in medical imaging. The aim of this study was to estimate patient radiation dose from SPECT myocardial perfusion imaging (MPI) using CT images for attenuation correction. Methods: SPECT and CT image acquisition parameters such as administered activity (AA), CT dose index (CTDIvol), and dose-length product for 415 patients who had undergone SPECT MPI using CT attenuation correction were reviewed. Effective dose (ED) for the SPECT part, the CT part and the total ED for the procedure were calculated. AA, CTDIvol, and ED values were compared between the 2 sexes and between body mass indexes (BMIs), imaging scanner models, and imaging centers. Statistical analyses were performed using t tests and 1-way ANOVA at P < 0.05 level of significance. Results: The range of AAs used for MPI was found to be 1,206-1,964 MBq per patient regardless of sex. The resulting mean ED of 8.8 mSv for men was significantly lower (P = 0.002) than the 10.4 mSv for women for SPECT. The range of CTDIvol was 1.12-3.97 mGy, resulting in an mean ED of 0.8 mSv for men, significantly lower (P < 0.001) than the 1.1 mSv for women for CT. The average combined EDs for male and female patients were 9.6 and 11.5 mSv, respectively. A positive correlation was found between AA and patient BMI (r = 0.48; P < 0.001), indicating patient size-related AAs. However, CTDIvol was found to depend only on the scanner model, regardless of BMI. Conclusion: The ED from SPECT/CT MPI studies was around 11 mSv, with 10 mSv being from the SPECT part of the study. The extra risk to the patients from CT imaging for attenuation correction is small compared with the benefit incurred from accurate diagnosis.

Current pediatric administered activity guidelines for 99m Tc-DMSA SPECT based on patient weight do not provide the same task-based image quality.

In the current clinical practice, administered activity (AA) for pediatric molecular imaging is often based on the North American expert consensus guidelines or the European Association of Nuclear Medicine dosage card, both of which were developed based on the best clinical practice. These guidelines were not formulated using a rigorous evaluation of diagnostic image quality (IQ) relative to AA. In the guidelines, AA is determined by a weight-based scaling of the adult AA, along with minimum and maximum AA constraints. In this study, we use task-based IQ assessment methods to rigorously evaluate the efficacy of weight-based scaling in equalizing IQ using a population of pediatric patients of different ages and body weights. A previously developed projection image database was used. We measured task-based IQ, with respect to the detection of a renal functional defect at six different AA levels (AA relative to the AA obtained from the guidelines). IQ was assessed using an anthropomorphic model observer. Receiver-operating characteristics (ROC) analysis was applied; the area under the ROC curve (AUC) served as a figure-of-merit for task performance. In addition, we investigated patient girth (circumference) as a potential improved predictor of the IQ. The data demonstrate a monotonic and modestly saturating increase in AUC with increasing AA, indicating that defect detectability was limited by quantum noise and the effects of object variability were modest over the range of AA levels studied. The AA for a given value of the AUC increased with increasing age. The AUC vs AA plots for all the patient ages indicate that, for the current guidelines, the newborn and 10- and 15-yr phantoms had similar IQ for the same AA suggested by the North American expert consensus guidelines, but the 5- and 1-yr phantoms had lower IQ. The results also showed that girth has a stronger correlation with the needed AA to provide a constant AUC for 99m Tc-DMSA renal SPECT. The results suggest that (a) weight-based scaling is not sufficient to equalize task-based IQ for patients of different weights in pediatric 99m Tc-DMSA renal SPECT; and (b) patient girth should be considered instead of weight in developing new administration guidelines for pediatric patients.

Estimating the population dose from nuclear medicine examinations towards establishing diagnostic reference levels.

Purpose of the Study:This study conducted a review on nuclear medicine (NM) services in Mazandaran Province with a view to establish adult diagnostic reference levels (DRLs) and provide updated data on population radiation exposure resulting from diagnostic NM procedures.Materials and Methods:The data were collected from all centers in all cities of Mazandaran Province in the North of Iran from March 2014 to February 2015. The 75th percentile of the distribution and the average administered activity (AAA) were calculated and the average effective dose per examination, collective effective dose to the population and annual effective dose per capita were estimated using dose conversion factors. The gathered data were analyzed via SPSS (version 18) software using descriptive statistics.Results:Based on the data of this study, the collective effective dose was 95.628 manSv, leading to a mean effective dose of 0.03 mSv per capita. It was also observed that the myocardial perfusion was the most common procedure (50%). The 75th percentile of the distribution of administered activity (AA) represents the DRL. The AAA and the 75th percentile of the distribution of AA are slightly higher than DRL of most European countries.Conclusions:Myocardial perfusion is responsible for most of the collective effective dose and it is better to establish national DRLs for myocardial perfusion and review some DRL values through the participation of NM specialists in the future.

Tumor Dosimetry and Response for 153Sm-Ethylenediamine Tetramethylene Phosphonic Acid Therapy of High-Risk Osteosarcoma

(153)Sm-ethylenediamine tetramethylene phosphonic acid ((153)Sm-EDTMP) therapy for osteosarcoma is being investigated. In this study, we analyzed the influence of (153)Sm-EDTMP administered activity (AA), osteosarcoma tumor density, mass, and the shape of the tumor on absorbed dose (AD). We also studied the biologic implication of the nonuniform tumor AD distribution using radiobiologic modeling and examined the relationship between tumor AD and response. Nineteen tumors in 6 patients with recurrent, refractory osteosarcoma enrolled in a phase I or II clinical trial of (153)Sm-EDTMP were analyzed using the 3-dimensional radiobiologic dosimetry (3D-RD) software package. Patients received a low dose of (153)Sm-EDTMP (37.0-51.8 MBq/kg), followed on hematologic recovery by a second, high dose (222 MBq/kg). Treatment response was evaluated using either CT or MRI after each therapy. SPECT/CT of the tumor regions were obtained at 4 and 48 h or 72 h after (153)Sm-EDTMP therapy for 3D-RD analysis. Mean tumor AD was also calculated using the OLINDA/EXM unit-density sphere model and was compared with the 3D-RD estimates. On average, a 5-fold increase in the AA led to a 4-fold increase in the mean tumor AD over the high- versus low-dose-treated patients. The range of mean tumor AD and equivalent uniform dose (EUD) for low-dose therapy were 1.48-14.6 and 0.98-3.90 Gy, respectively. Corresponding values for high-dose therapy were 2.93-59.3 and 1.89-12.3 Gy, respectively. Mean tumor AD estimates obtained from OLINDA/EXM were within 5% of the mean AD values obtained using 3D-RD. On an individual tumor basis, both mean AD and EUD were positively related to percentage tumor volume reduction (P = 0.031 and 0.023, respectively). The variations in tumor density, mass, and shape seen in these tumors did not affect the mean tumor AD estimation significantly. The tumor EUD was approximately 2- and 3-fold lower than the mean AD for low- and high-dose therapy, respectively. A dose-response relationship was observed for transient tumor volume shrinkage.

A Curve-Fitting Approach to Estimate the Arterial Plasma Input Function for the Assessment of Glucose Metabolic Rate and Response to Treatment

For the quantification of dynamic (18)F-FDG PET studies, the arterial plasma time-activity concentration curve (APTAC) needs to be available. This can be obtained using serial sampling of arterial blood or an image-derived input function (IDIF). Arterial sampling is invasive and often not feasible in practice; IDIFs are biased because of partial-volume effects and cannot be used when no large arterial blood pool is in the field of view. We propose a mathematic function, consisting of an initial linear rising activity concentration followed by a triexponential decay, to describe the APTAC. This function was fitted to 80 oncologic patients and verified for 40 different oncologic patients by area-under-the-curve (AUC) comparison, Patlak glucose metabolic rate (MR(glc)) estimation, and therapy response monitoring (Delta MR(glc)). The proposed function was compared with the gold standard (serial arterial sampling) and the IDIF. To determine the free parameters of the function, plasma time-activity curves based on arterial samples in 80 patients were fitted after normalization for administered activity (AA) and initial distribution volume (iDV) of (18)F-FDG. The medians of these free parameters were used for the model. In 40 other patients (20 baseline and 20 follow-up dynamic (18)F-FDG PET scans), this model was validated. The population-based curve, individually calibrated by AA and iDV (APTAC(AA/iDV)), by 1 late arterial sample (APTAC(1 sample)), and by the individual IDIF (APTAC(IDIF)), was compared with the gold standard of serial arterial sampling (APTAC(sampled)) using the AUC. Additionally, these 3 methods of APTAC determination were evaluated with Patlak MR(glc) estimation and with Delta MR(glc) for therapy effects using serial sampling as the gold standard. Excellent individual fits to the function were derived with significantly different decay constants (P < 0.001). Correlations between AUC from APTAC(AA/iDV), APTAC(1 sample), and APTAC(IDIF) with the gold standard (APTAC(sampled)) were 0.880, 0.994, and 0.856, respectively. For MR(glc), these correlations were 0.963, 0.994, and 0.966, respectively. In response monitoring, these correlations were 0.947, 0.982, and 0.949, respectively. Additional scaling by 1 late arterial sample showed a significant improvement (P < 0.001). The fitted input function calibrated for AA and iDV performed similarly to IDIF. Performance improved significantly using 1 late arterial sample. The proposed model can be used when an IDIF is not available or when serial arterial sampling is not feasible.