Comparison of plasma clearance of [51Cr]CrEDTA based on three, two and single samples to measure the glomerular filtration rate in patients with solid tumors: a prospective cross-sectional analysis.

OBJECTIVES: [51Cr]CrEDTA is used to measure the Glomerular Filtration Rate (GFR) in different clinical conditions. However, there is no consensus on the ideal number of blood samples to be taken and at what time points to measure its clearance. This study aimed to compare Slope Intercept (SI) and Single-Sample (SS) methods for measuring GFR in patients with solid tumors, stratified by age, GFR, and Body Mass Index (BMI). METHODS: 1,174 patients with cancer were enrolled in this prospective study. GFR was calculated by the SI method using blood samples drawn 2-, 4-, and 6-hours after [51Cr]CrEDTA injection (246-GFR). GFR was also measured using the SI method with samples at 2 and 4 hours (24-GFR) and at 4 and 6 hours (46-GFR), and SS methods according to Groth (4Gr-GFR) and Fleming (4Fl-GFR). Statistical analysis was performed to assess the accuracy, precision, and bias of the methods. RESULTS: Mean 246-GFR was 79.2 ± 21.9 mL/min/1.73 m2. ANOVA indicated a significant difference between 4Gr-GFR and the reference 246-GFR. Bias was lower than 5 mL/min/1.73 m2 for all methods, except for SS methods in subgroups BMI > 40 kg/m2; GFR > 105 or < 45. Precision was adequate and accuracy of 30 % was above 98% for all methods, except for SS methods in subgroup GFR < 45. CONCLUSION: 46-GFR and 246-GFR have high agreement and may be used to evaluate kidney function in patients with solid tumors. Single-sample methods can be adopted in specific situations, for non-obese patients with expected normal GFR.

Glomerular Filtration Rate Estimation Using ß2-Microglobulin and ß-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study.

RATIONALE & OBJECTIVE: ß2-Microglobulin (B2M) and ß-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFRcr-cys), but they have not been assessed in patients with cancer. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September 2017. EXPOSURE: CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR). OUTCOME: Performance of equations compared with eGFRcr-cys and non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). ANALYTICAL APPROACH: Bias was defined as the median of the differences between mGFR and eGFR, and 1-P30 was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). Linear regression was used to assess association of clinical and laboratory variables with SB2M, and SBTP after adjustment for mGFR. RESULTS: Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m2, respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys (lesser bias and 1-P30). Performance of 2-marker panel equations was as good as eGFRcr-cys (lesser bias and similar 1-P30). SB2M and SBTP were not strongly influenced by cancer site. LIMITATIONS: Participants may have had better clinical performance status than the general population of patients with solid tumors. CONCLUSIONS: B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine. PLAIN-LANGUAGE SUMMARY: The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using ß2-microglobulin (B2M) and/or ß-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

Optimized Monte Carlo simulations for voxel-based internal dosimetry.

Objective.The scientific community has considered internal dosimetry by the Monte Carlo method the gold standard. However, there is a trade-off between simulation processing time and the statistical quality of the results that makes it a challenge to obtain accurate absorbed dose values in some situations, such as dose estimation in organs affected by cross-irradiation or limited computing power. Variance reduction techniques are used to reduce computational processing time without impairing the statistical quality of the results, such as tracking energy cutoff, secondary particle production threshold, and parallelism of different types of emissions from radionuclides.Approach.In this work, GATE Monte Carlo code and its variance reduction techniques were evaluated to calculateSvalues of organs from the international commission on radiological protection (ICRP) report 110 male phantom for the lutetium-177, iodine-131, yttrium-90, and radium-223 radionuclides. The results are compared with the data from the OpenDose collaboration.Main results.A cutoff of 5 MeV for local electron deposition and 2.0 mm of secondary particle production range resulted in a computational efficiency increase of 7.9 and 1.05 times, respectively. Simulation of ICRP 107 spectra-based source proved to be about 5 times more efficient when compared to a decay simulation usingG4RadioactiveDecay(Geant4-based radioactive decay processes). Track length estimator (TLE) and split exponential track length estimator (seTLE) techniques were used to calculate the absorbed dose of photon emissions, resulting in computational efficiency up to 29.4 and 62.5 times higher when compared to traditional simulations, respectively. In particular, the seTLE technique accelerates the simulation time by up to 1426 times, achieving a statistical uncertainty of 10% in volumes affected by cross-irradiation.Significance.The variance reduction techniques used in this work drastically reduced the simulation time and maintained the statistical quality of the calculated absorbed dose values, proving the feasibility of the use of the Monte Carlo method in internal dosimetry under challenging situations and making it viable for clinical routine or web applications.

Influence on voxel-based dosimetry: noise effect on absorbed dose dosimetry at single time-point versus sequential single-photon emission computed tomography.

OBJECTIVE: The purpose of this study was to evaluate how statistical fluctuation in single-photon emission computed tomography (SPECT) images propagate to absorbed dose maps. METHODS: SPECT/computed tomography (CT) images of iodine-131 filled phantoms, using different acquisition and processing protocols, were evaluated using STRATOS software to assess the absorbed dose distribution at the voxel level. Absorbed dose values and coefficient of variation (COV) were analyzed for dosimetry based on single time-point SPECT images and time-integrated activities of SPECT sequences with low and high counts. RESULTS: Considering dosimetry based on a single time-point, the mean absorbed dose was not significantly affected by total counts or reconstruction parameters, but the uniformity of the absorbed dose maps had an almost linear correlation with SPECT noise. When high- and low-count SPECT sequences were used to generate an absorbed dose map, the absorbed dose COV for each of the temporal sequences was slightly lower than the absorbed dose COV based on the single SPECT image with the highest count included in the sequence. CONCLUSION: The impact of changes in SPECT counts and reconstruction parameters is almost linear when dosimetry is based on isolated SPECT images, but less pronounced when dosimetry is based on sequential SPECTs.

68Ga-PSMA-11 PET/MRI versus multiparametric MRI in men referred for prostate biopsy: primary tumour localization and interreader agreement.

BACKGROUND: Magnetic resonance imaging (MRI) is recommended by the European Urology Association guidelines as the standard modality for imaging-guided biopsy. Recently positron emission tomography with prostate-specific membrane antigen (PSMA PET) has shown promising results as a tool for this purpose. The aim of this study was to compare the accuracy of positron emission tomography with prostate-specific membrane antigen/magnetic resonance imaging (PET/MRI) using the gallium-labeled prostate-specific membrane antigen (68Ga-PSMA-11) and multiparametric MRI (mpMRI) for pre-biopsy tumour localization and interreader agreement for visual and semiquantitative analysis. Semiquantitative parameters included apparent diffusion coefficient (ADC) and maximum lesion diameter for mpMRI and standardized uptake value (SUVmax) and PSMA-positive volume (PSMAvol) for PSMA PET/MRI. RESULTS: Sensitivity and specificity were 61.4% and 92.9% for mpMRI and 66.7% and 92.9% for PSMA PET/MRI for reader one, respectively. RPE was available in 23 patients and 41 of 47 quadrants with discrepant findings. Based on RPE results, the specificity for both imaging modalities increased to 98% and 99%, and the sensitivity improved to 63.9% and 72.1% for mpMRI and PSMA PET/MRI, respectively. Both modalities yielded a substantial interreader agreement for primary tumour localization (mpMRI kappa = 0.65 (0.52-0.79), PSMA PET/MRI kappa = 0.73 (0.61-0.84)). ICC for SUVmax, PSMAvol and lesion diameter were almost perfect (≥ 0.90) while for ADC it was only moderate (ICC = 0.54 (0.04-0.78)). ADC and lesion diameter did not correlate significantly with Gleason score (ρ = 0.26 and ρ = 0.16) while SUVmax and PSMAvol did (ρ = - 0.474 and ρ = - 0.468). CONCLUSIONS: PSMA PET/MRI has similar accuracy and reliability to mpMRI regarding primary prostate cancer (PCa) localization. In our cohort, semiquantitative parameters from PSMA PET/MRI correlated with tumour grade and were more reliable than the ones from mpMRI.

A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors.

Current guidelines recommend estimating glomerular filtration rate (eGFR) using creatinine (eGFRcr) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as the first test for GFR evaluation, but the Cockcroft-Gault (CG) equation is still commonly used in oncology practice and clinical trials despite increasing evidence of its inaccuracy compared to measured GFR (mGFR). Guidelines recommend eGFR using cystatin C (eGFRcys) or both markers (eGFRcr-cys) as a confirmatory test, but neither was carefully evaluated in cancer patients. Therefore, we compared performance of the CKD-EPI equations and others to the CG equation in adults with a variety of solid tumors. The mGFR was determined by plasma clearance of 51Cr-EDTA. Bias was defined as the median of the differences between mGFR and eGFR while accuracy was defined as the percentage of estimates that differed by more than 30% from the measured GFR (1-P30). We prospectively recruited 1,200 patients between April 2015 and September 2017 with a mean age and mGFR of 58.8 years and 78.4 ml/min/1.73m2, respectively. Bias among eGFRcr equations varied from -8.1 to +6.1 ml/min/1.73 m2. CG was the least accurate, 1-P30 (95% confidence interval) was 24.9 (22.4- 27.3)%; CKD-EPI had 1-P30 of 19.1 (16.8-21.2)% while eGFRcr-cys had the best performance: bias -2.0 (-2.6 to -1.1) ml/min/1.73m2 and 1-P30 7.8 (6.3-9.4)%. Thus, the CG equation should not be preferred over CKD-EPI equation, and eGFRcr-cys can be used as a confirmatory test in adults with solid tumors. Hence, a major policy implication would be to adopt general practice guideline-recommended methods for GFR evaluation in oncology practice and clinical trials.

Hot needles can confirm accurate lesion sampling intraoperatively using [18F]PSMA-1007 PET/CT-guided biopsy in patients with suspected prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [68 Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [18F]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling. METHODS: In this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [18F]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 ± 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson's test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC). RESULTS: In 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 ± 396 cpm) compared to needles without PCa (73 ± 44 cpm, p < 0.001). In one patient with moderate PSMA uptake (SUVmax 8.7), 13 out of 24 needles had increased counts (100-200 cpm) but only signs of inflammation and PSMA expression in benign glands on IHC. Excluding this case, ROC analysis resulted in an AUC of 0.81, with an optimal cut-off to confirm PCa at 75 cpm (sens/spec of 65.1%/87%). In all 4 patients with PCa, the first or second PSMA PET-guided needle was positive for sigPCa with high counts (156-2079 cpm). CONCLUSIONS: [18F]PSMA-1007 uptake in PCa can be used to confirm accurate lesion sampling of the dominant tumor intraoperatively. This technique could improve confidence in imaging-based biopsy guidance and reduce the need for saturation biopsy. TRIAL REGISTRATION NUMBER: NCT03187990, 15/06/2017.

Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial.

BACKGROUND: Sarcopenia plays a central role in the development of frailty syndrome. Nutrition and exercise are cornerstone strategies to mitigate the transition to frailty; however, there is a paucity of evidence for which dietary and exercise strategies are effective. OBJECTIVE: This large, multifactorial trial investigated the efficacy of different dietary strategies to enhance the adaptations to resistance training in pre-frail and frail elderly. METHODS: This was a single-site 16-week, double-blind, randomized, placebo-controlled trial conducted at the Clinical Hospital, School of Medicine - University of São Paulo, Sao Paulo, Brazil. Four integrated, sub-investigations were conducted to compare: 1) leucine vs. placebo; 2) whey vs. soy vs. placebo; 3) creatine vs. whey vs. creatine plus whey vs. placebo; 4) women vs. men in response to whey. Sub-investigations 1 to 3 were conducted in women, only. Two-hundred participants (154 women/46 men, mean age 72 ± 6 years) underwent a twice-a-week, resistance training program. The main outcomes were muscle function (assessed by dynamic and isometric strength and functional tests) and lean mass (assessed by DXA). Muscle cross-sectional area, health-related quality of life, bone and fat mass, and biochemical markers were also assessed. RESULTS: We observed that leucine supplementation was ineffective to improve muscle mass and function. Supplementation with whey and soy failed to enhance resistance-training effects. Similarly, supplementation with neither whey nor creatine potentiated the adaptations to resistance training. Finally, no sex-based differences were found in response to whey supplementation. Resistance exercise per se increased muscle mass and function in all sub-investigations. There were no adverse effects. CONCLUSION: Neither protein (whey and soy), leucine, nor creatine supplementation enhanced resistance training-induced adaptations in pre-frail and frail elderly, regardless of sex. These findings do not support the notion that some widely used supplement-based interventions can add to the already potent effects of resistance exercise to counteract frailty-related muscle wasting and dynapenia. CLINICAL TRIAL REGISTRY: NCT01890382; https://clinicaltrials.gov/ct2/show/NCT01890382. DATA SHARING: Data described in the manuscript will be made available upon request pending application.

General Concepts in Theranostics.

Theranostics describes the pairing of diagnostic biomarkers and therapeutic agents with common specific targets. Nuclear medicine is the greatest theranostics protagonist, relying on radioactive tracers for imaging biologic phenomena and delivering ionizing radiation to the tissues that take up those tracers. The concept has gained importance with the growth of personalized medicine, allowing customized management for diseases, refining patient selection, better predicting responses, reducing toxicity, and estimating prognosis. This work provides an overview of the general concepts of the theranostics approach in nuclear medicine discussing its background, features, and future directions in imaging and therapy.

Diagnostic performance of 68Ga-PSMA-11 PET/MRI-guided biopsy in patients with suspected prostate cancer: a prospective single-center study.

PURPOSE: Ultrasound-guided biopsy (US biopsy) with 10-12 cores has a suboptimal sensitivity for clinically significant prostate cancer (sigPCa). If US biopsy is negative, magnetic resonance imaging (MRI)-guided biopsy is recommended, despite a low specificity for lesions with score 3-5 on Prostate Imaging Reporting and Data System (PIRADS). Screening and biopsy guidance using an imaging modality with high accuracy could reduce the number of unnecessary biopsies, reducing side effects. The aim of this study was to assess the performance of positron emission tomography/MRI with 68Ga-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length ≥ 6 mm) and guide biopsy. METHODS: Prospective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS ≥3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard. RESULTS: SigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy. CONCLUSION: PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy. TRIAL REGISTRATION: This trial was retrospectively registered under the name "Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Guided Biopsy in Men with Elevated PSA" (NCT03187990) on 06/15/2017 ( https://clinicaltrials.gov/ct2/show/NCT03187990 ).

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Burden of metastatic bone disease measured on 18F-NaF PET/computed tomography studies as a prognostic indicator in patients with medullary thyroid cancer.

PURPOSE: The aim of the study was to assess the association between the burden of metastatic bone disease measured on F-NaF PET/computed tomography (CT) studies and the overall survival (OS) of patients with medullary thyroid cancer (MTC). METHODS: We retrospectively analyzed 31 patients with MTC who performed 18F-NaF PET/CT studies to assess skeletal metastases. The outcomes of the patients (dead or alive) were established based on the last information available on their files. In the studies considered positives for skeletal metastases, the burden of metastatic bone disease was established calculating the fluoride tumor volume (FTV). The FTV was defined using isocontour thresholds based on percentages of maximal standardized uptake values (SUVmax) in the lesions. These percentages varied from lesion to lesion and were established by visual analysis. The patients were divided into three groups as follows: without skeletal metastases (n = 11), with low FTV (≤50 cm; n = 11) and with high FTV (>50cm; n = 9). The Kaplan-Meier curves were used to analyze the OS in the three groups of patients and the log-rank test was used to determine the statistical significance of the difference between the groups. RESULTS: There were statistically significant differences in the OS between the group with high FTV and the groups of patients with low FTV (P = 0.036) and without skeletal metastases (P = 0.001). There was not a statistically significant difference between the groups of patients with low FTV and without skeletal metastases (P = 0.147). CONCLUSION: In patients with MTC, the burden of metastatic bone disease is associated with OS.

68Ga-DOTATATE PET: temporal variation of maximum standardized uptake value in normal tissues and neuroendocrine tumours.

OBJECTIVES: Higher affinity of Ga compounds to somatostatin receptors (SSTRs) and PET better image resolution increased interest in Ga-labelled somatostatin analogs in the management of neuroendocrine tumours (NETs). This study aimed to evaluate the maximum standardized uptake value (SUVmax) variation in sequential somatostatin analogs-PET in NET patients and identify optimal tumour detection and characterization imaging time. METHODS: Patients with histological or biochemical NET diagnosis performed two to three PET/computed tomography (CT) scans after intravenous injection of Ga-DOTATATE: Early PET [EarlyPET: <15 minutes postinjection (p.i.)], diagnostic PET (DiagPET: 45-90 minutes p.i.) and delayed PET (DelayPE: 90-240 minutes p.i.). Up to five tumour sites and normal tissues had SUVmax determined. Time-SUVmax curves were created for the target lesions and normal organs. Ratios between tumour and liver SUVmax (SUVTU/Liver) and tumour/blood pool (SUVTU/BP) were also calculated. RESULTS: Twenty-nine patients were included, 16 female, mean age of 46.5 ± 14.3 years. Average administered activity was 129.5 ± 29.6 MBq. Kidneys SUVmax was higher in EarlyPET compared with DiagPET (P = 0.04) and DelayPET showed higher SUVmax compared with DiagPET for normal liver, pancreas and kidneys (P = 0.02). No differences were noted between EarlyPET, DiagPET and DelayPET in tumour SUVmax (P > 0.05). SUVTU/Liver and SUVTU/BP did not change between EarlyPET and DiagPET, with a slight decrease in DelayPET. CONCLUSION: Stability in tumour SUVmax values measured at different intervals independently of tumour location, as also in normal tissues as kidneys and liver suggest that a more flexible imaging protocol may be adopted.

Melatonin Increases Brown Adipose Tissue Volume and Activity in Patients With Melatonin Deficiency: A Proof-of-Concept Study.

Melatonin, a pineal hormone synthesized at night, is critical for the synchronization of circadian and seasonal rhythms, being a key regulator of energy metabolism in many animal species. Although studies in humans are lacking, several reports, mainly on hibernating animals, demonstrated that melatonin supplementation and a short photoperiod increase brown adipose tissue (BAT) mass. The present proof-of-concept study is the first, to our knowledge, to evaluate BAT in patients with melatonin deficiency (radiotherapy or surgical removal of pineal gland) before and after daily melatonin (3 mg) replacement for 3 months. All four studied patients presented increased BAT volume and activity measured by positron emission tomography-MRI. We also found an improvement in total cholesterol and triglyceride blood levels without significant effects on body weight, liver fat, and HDL and LDL levels. Albeit not statistically significant, fasting insulin levels and HOMA of insulin resistance decreased in all four patients. The present results show that oral melatonin replacement increases BAT volume and activity and improves blood lipid levels in patients with melatonin deficiency, suggesting that melatonin is a possible BAT activator. Future studies are warranted because hypomelatoninemia is usually present in aging and appears as a result of light-at-night exposure and/or the use of ß-blocker drugs.

Diagnostic reference level: an important tool for reducing radiation doses in adult and pediatric nuclear medicine procedures in Brazil.

OBJECTIVES: This study aimed to establish a concise method for determining a diagnostic reference level (DRL) for adult and pediatric nuclear medicine patients on the basis of diagnostic procedures and administered radioisotope as a means of controlling medical exposure. METHODS: A screening was carried out in all Brazilian Nuclear Medicine Service (NMS) establishments to support this study by collecting the average activities administered during adult diagnostic procedures and the rules applied to adjust these according to the patient's age and body mass. Percentile 75 was used in all the activities administered as a means of establishing DRL for adult patients, with additional correction factors for pediatric patients. Radiation doses from nuclear medicine procedures on the basis of average administered activity were calculated for all diagnostic exams. RESULTS AND DISCUSSION: A total of 107 NMSs in Brazil agreed to participate in the project. From the 64 nuclear medicine procedures studied, bone, kidney, and parathyroid scans were found to be used in more than 85% of all the NMSs analyzed. There was a large disparity among the activities administered, when applying the same procedures, this reaching, in some cases, more than 20 times between the lowest and the highest. Diagnostic exams based on Ga, Tl, and I radioisotopes proved to be the major exams administering radiation doses to patients. On introducing the DRL concept into clinical routine, the minimum reduction in radiation doses received by patients was about 15%, the maximum was 95%, and the average was 50% compared with the previously reported administered activities. CONCLUSION: Variability in the available diagnostic procedures as well as in the amount of activities administered within the same procedure was appreciable not only in Brazil, but worldwide. Global efforts are needed to establish a concise DRL that can be applied in adult and pediatric nuclear medicine procedures as the application of DRL in clinical routine has been proven to be an important tool for controlling and reducing radiation doses received by patients in medical exposure.

Prediction of iodine-131 biokinetics and radiation doses from therapy on the basis of tracer studies: an important question for therapy planning in nuclear medicine.

OBJECTIVES: This study aimed to present a comparison of iodine-131 (I) biokinetics and radiation doses to red-marrow (rm) and whole-body (wb), following the administration of tracer and therapeutic activities, as a means of confirming whether I clearance and radiation doses for therapy procedures can be predicted by tracer activities. METHODS: Eleven differentiated thyroid cancer patients were followed after receiving tracer and therapeutic I activity. Whole-body I clearance was estimated using radiation detectors and OLINDA/EXM software was used to calculate radiation doses to rm and wb. RESULTS AND DISCUSSION: Tracer I activity of 86 (±14) MBq and therapeutic activity of 8.04 (±1.18) GBq were administered to patients, thereby producing an average wb I effective half-time and residence time of, respectively, 13.51 (±4.05) and 23.13 (±5.98) h for tracer activities and 13.32 (±3.38) and 19.63 (±4.77) h for therapy. Radiation doses to rm and wb were, respectively, 0.0467 (±0.0208) and 0.0589 (±0.0207) mGy/MBq in tracer studies and 0.0396 (±0.0169) and 0.0500 (±0.0163) mGy/MBq in therapy. Although the differences were not considered statistically significant between averages, those between the values of effective half-times (P=0.906), residence times (P=0.145), and radiation doses to rm (P=0.393) and to wb (P=0.272), from tracer and therapy procedures, large differences of up to 80% in wb I clearance, and up to 50% in radiation doses were observed when patients were analyzed individually, thus impacting on the total amount of I activity calculated to be safe for application in individual therapy. CONCLUSION: I biokinetics and radiation doses to rm and wb in therapy procedures are well predicted by diagnostic activities when average values of a group of patients are compared. Nonetheless, when patients are analyzed individually, significant differences may be encountered, thus implying that nuclear medicine therapy-planning requires due consideration of changes in individual patient-body status from initial tracer to final therapy procedures to thus provide appropriate adjustments in therapeutic activities.

Dose Calibrator Linearity Testing: Radioisotope (99m)Tc or (18)F? An Alternative for Reducing Costs in Nuclear Medicine Quality Control.

Dose calibrator linearity testing is indispensable for evaluating the capacity of this equipment in measuring radioisotope activities at different magnitudes, a fundamental aspect of the daily routine of a nuclear medicine department, and with an impact on patient exposure. The main aims of this study were to evaluate the feasibility of substituting the radioisotope Fluorine-18 ((18)F) with Technetium-99m ((99m)Tc) in this test, and to indicate it with the lowest operational cost. The test was applied with sources of (99m)Tc (62 GBq) and (18)F (12 GBq), the activities of which were measured at different times, with the equipment preadjusted to measuring sources of (99m)Tc, (18)F, Gallium-67 ((67)Ga), and Iodine-131 ((131)I). Over time, the average deviation between measured and expected activities from (99m)Tc and (18)F were, respectively, 0.56 (±1.79)% and 0.92 (±1.19)%. The average ratios for 99(m)Tc source experimental activity, when measured with the equipment adjusted for measuring (18)F, (67)Ga, and (131)I sources, in real values, were, respectively, 3.42 (±0.06), 1.45 (±0.03), and 1.13 (±0.02), and those for the (18)F source experimental activity, measured through adjustments of (99m)Tc, (67)Ga, and (131)I, were, respectively, 0.295 (±0.004), 0.335 (±0.007), and 0.426 (±0.006). The adjustment of a simple exponential function for describing (99m)Tc and (18)F experimental activities facilitated the calculation of the physical half-lives of the radioisotopes, with a difference of about 1% in relation to the values described in the literature. Linearity test results, when using (99m)Tc, through being compatible with those acquired with (18)F, imply the possibility of using both radioisotopes during linearity testing. Nevertheless, this information, along with the high potential of exposure and the high cost of (18)F, implies that (99m)Tc should preferably be employed for linearity testing in clinics that normally use (18)F, without the risk of prejudicing either the procedure itself or the guarantee of a high-quality nuclear medicine service.

Determining thyroid (131)I effective half-life for the treatment planning of Graves' disease.

PURPOSE: Thyroid (131)I effective half-life (T(eff)) is an essential parameter in patient therapy when accurate radiation dose is desirable for producing an intended therapeutic outcome. Multiple (131)I uptake measurements and resources from patients themselves and from nuclear medicine facilities are requisites for determining T(eff), these being limiting factors when implementing the treatment planning of Graves' disease (GD) in radionuclide therapy. With the aim of optimizing this process, this study presents a practical, propitious, and accurate method of determining T(eff) for dosimetric purposes. METHODS: A total of 50 patients with GD were included in this prospective study. Thyroidal (131)I uptake was measured at 2-h, 6-h, 24-h, 48-h, 96-h, and 220-h postradioiodine administration. T(eff) was calculated by considering sets of two measured points (24-48-h, 24-96-h, and 24-220-h), sets of three (24-48-96-h, 24-48-220-h, and 24-96-220-h), and sets of four (24-48-96-220-h). RESULTS: When considering all the measured points, the representative T(eff) for all the patients was 6.95 (±0.81) days, whereas when using such sets of points as (24-220-h), (24-96-220-h), and (24-48-220-h), this was 6.85 (±0.81), 6.90 (±0.81), and 6.95 (±0.81) days, respectively. According to the mean deviations 2.2 (±2.4)%, 2.1 (±2.0)%, and 0.04 (±0.09)% found in T(eff), calculated based on all the measured points in time, and with methods using the (24-220-h), (24-48-220-h), and (24-96-220-h) sets, respectively, no meaningful statistical difference was noted among the three methods (p > 0.500, t test). CONCLUSIONS: T(eff) obtained from only two thyroid (131)I uptakes measured at 24-h and 220-h, besides proving to be sufficient, accurate enough, and easily applicable, attributes additional major cost-benefits for patients, and facilitates the application of the method for dosimetric purposes in the treatment planning of Graves' disease.