In vivo assessment of safety, biodistribution, and radiation dosimetry of the [18F]Me4FDG PET-radiotracer in adults.

BACKGROUND: Approaches targeting the sodium-glucose cotransporter (SGLT) could represent a promising future therapeutic strategy for numerous oncological and metabolic diseases. In this study, we evaluated the safety, biodistribution and radiation dosimetry of the glucose analogue positron emission tomography (PET) agent [18F] labeled alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside ([18F]Me4FDG) with high sodium-glucose cotransporter and low glucose transporter (GLUT) affinity. For this purpose, five healthy volunteers (1 man, 4 women) underwent multiple whole-body PET/computed tomography (CT) examinations starting with injection and up to 4 h after injection of averaged (2.4 ± 0.1) MBq/kg (range: 2.3-2.5 MBq/kg) administered activity. The PET/CT scans were conducted in 5 separate sessions, blood pressure and temperature were measured, and blood and urine samples were collected before the scans and one hour after injection to assess toxicity. Measurements of [18F]Me4FDG radioactivity in organs of interest were determined from the PET/CT scans at 5 time points. Internal dosimetry was performed on voxel level using a fast Monte Carlo approach. RESULTS: All studied volunteers could well tolerate the [18F]Me4FDG and no adverse event was reported. The calculated effective dose was (0.013 ± 0.003) mSv/MBq. The organs with the highest absorbed dose were the kidneys with 0.05 mSv/MBq per kidney. The brain showed almost no uptake. After 60 min, (12 ± 15) % of the administered dose was excreted into the bladder. CONCLUSION: Featuring an effective dose of only 0.013 ± 0.003 mSv/MBq and no occurrence of side effects, the glucose analogue [18F]Me4FDG seems to be a safe radio-tracer with a favorable biodistribution for PET imaging and also within several consecutive scans. TRIAL REGISTRATION NUMBER: NCT03557138, Registered 22 February 2017, https://ichgcp.net/clinical-trials-registry/NCT03557138 .

Assessment of PSMA Expression of Healthy Organs in Different Stages of Prostate Cancer Using [68Ga]Ga-PSMA-11-PET Examinations.

The efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is currently being investigated for its application in patients with early-stage prostate cancer (PCa). However, little is known about PSMA expression in healthy organs in this cohort. Collectively, 202 [68Ga]Ga-PSMA-11 positron emission tomography (PET) scans from 152 patients were studied. Of these, 102 PET scans were from patients with primary PCa and hormone-sensitive biochemically recurrent PCa and 50 PET scans were from patients with metastatic castration-resistant PCa (mCRPC) before and after three cycles of [177Lu]Lu-PSMA-RLT. PSMA-standardized uptake values (SUV) were measured in multiple organs and PSMA-total tumor volume (PSMA-TTV) was determined in all cohorts. The measured PET parameters of the different cohorts were normalized to the bloodpool and compared using t- or Mann-Whitney U tests. Patients with early-stage PCa had lower PSMA-TTVs (10.39 mL vs. 462.42 mL, p < 0.001) and showed different SUVs in the thyroid, submandibular glands, heart, liver, kidneys, intestine, testes and bone marrow compared to patients with advanced CRPC, with all tests showing p < 0.05. Despite the differences in the PSMA-TTV of patients with mCRPC before and after [177Lu]Lu-PSMA-RLT (462.42 mL vs. 276.29 mL, p = 0.023), no significant organ differences in PET parameters were detected. These suggest different degrees of PSMA-ligand binding among patients with different stages of PCa that could influence radiotoxicity during earlier stages of disease in different organs when PSMA-RLT is administered.

A fingerprint of 2-[18F]FDG radiometabolites - How tissue-specific metabolism beyond 2-[18F]FDG-6-P could affect tracer accumulation.

Studies indicate that the radiotracer 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) can be metabolized beyond 2-[18F]FDG-6-phosphate (2-[18F]FDG-6-P), but its metabolism is incompletely understood. Most importantly, it remains unclear whether downstream metabolism affects tracer accumulation in vivo. Here we present a fingerprint of 2-[18F]FDG radiometabolites over time in cancer cells, corresponding tumor xenografts and murine organs. Strikingly, radiometabolites representing glycogen metabolism or the oxPPP correlated inversely with tracer accumulation across all examined tissues. Recent studies suggest that not only hexokinase, but also hexose-6-phosphate dehydrogenase (H6PD), an enzyme of the oxidative pentose phosphate pathway (oxPPP), determines 2-[18F]FDG accumulation. However, little is known about the corresponding enzyme glucose-6-phosphate dehydrogenase (G6PD). Our mechanistic in vitro experiments on the role of the oxPPP propose that 2-[18F]FDG can be metabolized via both G6PD and H6PD, but data from separate enzyme knockdown suggest diverging roles in downstream tracer metabolism. Overall, we propose that tissue-specific metabolism beyond 2-[18F]FDG-6-P could matter for imaging.

Direct Patlak Reconstruction of [68Ga]Ga-PSMA PET for the Evaluation of Primary Prostate Cancer Prior Total Prostatectomy: Results of a Pilot Study.

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3-130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [68Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [68Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa.

Excretion of glucose analogue with SGLT2 affinity predicts response effectiveness to sodium glucose transporter 2 inhibitors in patients with type 2 diabetes mellitus.

PURPOSE: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) regulation, developed as treatment for patients with type 2 diabetes, can be imaged with the glucose analogue alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside (Me4FDG), a positron emission tomography (PET) tracer with a high affinity for SGLT1 and SGLT2 proteins. With regard to therapy effectiveness, we aimed to investigate whether clinical parameters or Me4FDG excretion could predict response to SGLT2i in patients with type 2 diabetes. METHODS: In a longitudinal, prospective study, 19 patients with type 2 diabetes underwent Me4FDG combined PET and magnetic resonance imaging (PET/MRI) scans at baseline and 2 weeks after initiation of therapy with SGLT2i, accompanied by the collection of blood and urine samples. Me4FDG-excretion was determined from the Me4FDG uptake in the bladder. Long-term response was determined by HbA1c level after 3 months; a strong response to the therapy was defined as a reduction of HbA1c by at least 10% from baseline. RESULTS: SGLT2i resulted in significantly increased Me4FDG excretion (4.8 vs. 45.0, P < 0.001) and urine glucose (56 vs. 2806 mg/dl, P < 0.001). Baseline urine glucose and baseline Me4FDG excretion correlated both with long-term decline in HbA1c with r = 0.55 (P < 0.05). However, only Me4FDG excretion was a predictor of a strong response to SGLT2i (P = 0.005, OR 1.9). CONCLUSIONS: Using Me4FDG-PET, we demonstrated for the first time renal SGLT2-related excretion before and after short-term SGLT2i treatment. In contrary to other clinical parameters, SGLT2-related excretion before treatment was a robust predictor of long-term HbA1c response in patients with type 2 diabetes, suggesting that therapy effectiveness is only dependent of endogenous SGLT2 processes.

Whole-body metabolic connectivity framework with functional PET.

The nervous and circulatory system interconnects the various organs of the human body, building hierarchically organized subsystems, enabling fine-tuned, metabolically expensive brain-body and inter-organ crosstalk to appropriately adapt to internal and external demands. A deviation or failure in the function of a single organ or subsystem could trigger unforeseen biases or dysfunctions of the entire network, leading to maladaptive physiological or psychological responses. Therefore, quantifying these networks in healthy individuals and patients may help further our understanding of complex disorders involving body-brain crosstalk. Here we present a generalized framework to automatically estimate metabolic inter-organ connectivity utilizing whole-body functional positron emission tomography (fPET). The developed framework was applied to 16 healthy subjects (mean age ± SD, 25 ± 6 years; 13 female) that underwent one dynamic 18F-FDG PET/CT scan. Multiple procedures of organ segmentation (manual, automatic, circular volumes) and connectivity estimation (polynomial fitting, spatiotemporal filtering, covariance matrices) were compared to provide an optimized thorough overview of the workflow. The proposed approach was able to estimate the metabolic connectivity patterns within brain regions and organs as well as their interactions. Automated organ delineation, but not simplified circular volumes, showed high agreement with manual delineation. Polynomial fitting yielded similar connectivity as spatiotemporal filtering at the individual subject level. Furthermore, connectivity measures and group-level covariance matrices did not match. The strongest brain-body connectivity was observed for the liver and kidneys. The proposed framework offers novel opportunities towards analyzing metabolic function from a systemic, hierarchical perspective in a multitude of physiological pathological states.

Effects of Early Toilet Training and Elimination Communication With Respect to Diaper Types.

To investigate effects of diaper-free times, elimination communication (EC) and early toilet training, a web-based survey was conducted for caregivers. The more diaper-free times an infant experienced during day, the earlier it was toilet trained (P < .001), which was enhanced by the usage of cloth diapers. The amount of diaper-free times significantly reduced the caregiver's continuous sleep, the occurrence of rashes and balm usage (P < .001) and lead to a more regular defecation frequency. Cloth diaper usage had no effect on rashes or balm usage, but on diaper change rate (P < .001). We could show that, although not as effective as full-time EC, part-time EC is more effective if cloth diapers are used, provided they are changed frequently. Furthermore, EC causes a more regular defecation in infants between 1 and 2 years.

Simultaneous radiomethylation of [11C]harmine and [11C]DASB and kinetic modeling approach for serotonergic brain imaging in the same individual.

Simultaneous characterization of pathologies by multi-tracer positron emission tomography (PET) is among the most promising applications in nuclear medicine. Aim of this work was the simultaneous production of two PET-tracers in one module and test the relevance for human application. [11C]harmine and [11C]DASB were concurrently synthesized in a 'two-in-one-pot' reaction in quality for application. Dual-tracer protocol was simulated using 16 single PET scans in different orders of tracer application separated by different time intervals. Volume of distribution was calculated for single- and dual-tracer measurements using Logan's plot and arterial input function in 13 brain regions. The 'two-in-one-pot' reaction yielded equivalent amounts of both radiotracers with comparable molar activities. The simulations of the dual-tracer application were comparable to the single bolus injections in 13 brain regions, when [11C]harmine was applied first and [11C]DASB second, with an injection time interval of 45 min (rxy = 0.90). Our study shows the successful simultaneous dual-tracer production leading to decreased radiation burden and costs. The simulation of dual subject injection to quantify the monoamine oxidase-A and serotonin transporter distribution proved its high potential. Multi-tracer imaging may drive more sophisticated study designs and diminish the day-to-day differences in the same individual as well as increase PET scanner efficiency.

If It Works, Don't Touch It? A Cell-Based Approach to Studying 2-[18F]FDG Metabolism.

The glucose derivative 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) is still the most used radiotracer for positron emission tomography, as it visualizes glucose utilization and energy demand. In general, 2-[18F]FDG is said to be trapped intracellularly as 2-[18F]FDG-6-phosphate, which cannot be further metabolized. However, increasingly, this dogma is being questioned because of publications showing metabolism beyond 2-[18F]FDG-6-phosphate and even postulating 2-[18F]FDG imaging to depend on the enzyme hexose-6-phosphate dehydrogenase in the endoplasmic reticulum. Therefore, we aimed to study 2-[18F]FDG metabolism in the human cancer cell lines HT1080, HT29 and Huh7 applying HPLC. We then compared 2-[18F]FDG metabolism with intracellular tracer accumulation, efflux and the cells' metabolic state and used a graphical Gaussian model to visualize metabolic patterns. The extent of 2-[18F]FDG metabolism varied considerably, dependent on the cell line, and was significantly enhanced by glucose withdrawal. However, the metabolic pattern was quite conserved. The most important radiometabolites beyond 2-[18F]FDG-6-phosphate were 2-[18F]FDMannose-6-phosphate, 2-[18F]FDG-1,6-bisphosphate and 2-[18F]FD-phosphogluconolactone. Enhanced radiometabolite formation under glucose reduction was accompanied by reduced efflux and mirrored the cells' metabolic switch as assessed via extracellular lactate levels. We conclude that there can be considerable metabolism beyond 2-[18F]FDG-6-phosphate in cancer cell lines and a comprehensive understanding of 2-[18F]FDG metabolism might help to improve cancer research and tumor diagnosis.

Dynamic 18F-FDG PET imaging of liver lesions: evaluation of a two-tissue compartment model with dual blood input function.

BACKGROUND: Dynamic PET with kinetic modeling was reported to be potentially helpful in the assessment of hepatic malignancy. In this study, a kinetic modeling analysis was performed on hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) from dynamic FDG positron emission tomography/computer tomography (PET/CT) scans. METHODS: A reversible two-tissue compartment model with dual blood input function, which takes into consideration the blood supply from both hepatic artery and portal vein, was used for accurate kinetic modeling of liver dynamic 18F-FDG PET imaging. The blood input functions were directly measured as the mean values over the VOIs on descending aorta and portal vein respectively. And the contribution of hepatic artery to the blood input function was optimization-derived in the process of model fitting. The kinetic model was evaluated using dynamic PET data acquired on 24 patients with identified hepatobiliary malignancy. 38 HCC or ICC identified lesions and 24 healthy liver regions were analyzed. RESULTS: Results showed significant differences in kinetic parameters [Formula: see text], blood supplying fraction [Formula: see text], and metabolic rate constant [Formula: see text] between malignant lesions and healthy liver tissue. And significant differences were also observed in [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] between HCC and ICC lesions. Further investigations of the effect of SUV measurements on the derived kinetic parameters were conducted. And results showed comparable effectiveness of the kinetic modeling using either SUVmean or SUVmax measurements. CONCLUSIONS: Dynamic 18F-FDG PET imaging with optimization-derived hepatic artery blood supply fraction dual-blood input function kinetic modeling can effectively distinguish malignant lesions from healthy liver tissue, as well as HCC and ICC lesions.

A methodological investigation of healthy tissue, hepatocellular carcinoma, and other lesions with dynamic 68Ga-FAPI-04 PET/CT imaging.

BACKGROUND: The study aimed to establish a 68Ga-FAPI-04 kinetic model in hepatic lesions, to determine the potential role of kinetic parameters in the differentiation of hepatocellular carcinoma (HCC) from non-HCC lesions. MATERIAL AND METHODS: Time activity curves (TACs) were extracted from seven HCC lesions and five non-HCC lesions obtained from 68Ga-FAPI-04 dynamic positron emission tomography (PET) scans of eight patients. Three kinetic models were applied to the TACs, using image-derived hepatic artery and/or portal vein as input functions. The maximum standardized uptake value (SUVmax) was taken for the lesions, the hepatic artery, and for the portal veins-the mean SUV for all healthy regions. The optimum model was chosen after applying the Schwartz information criteria to the TACs, differences in model parameters between HCC, non-HCC lesions, and healthy tissue were evaluated with the ANOVA test. RESULTS: A reversible two-tissue compartment model using both the arterial as well as venous input function was most preferred and showed significant differences in the kinetic parameters VND, VT, and BPND between HCC, non-HCC lesions, and healthy regions (p < 0.01). CONCLUSION: Several model parameters derived from a two-tissue compartment kinetic model with two image-derived input function from vein and aorta and using SUVmax allow a differentiation between HCC and non-HCC lesions, obtained from dynamically performed PET scans using FAPI.

Dynamic 2-deoxy-2[18F] fluoro-D-glucose PET/MRI in human renal allotransplant patients undergoing acute kidney injury.

Patients after solid organ kidney transplantation (KTX) often suffer from acute kidney injury (AKI). Parameters as serum creatinine indicate a loss of kidney function, although no distinction of the cause and prognosis can be made. Imaging tools measuring kidney function have not been widely in clinical use. In this observational study we evaluated 2-deoxy-2[18F] fluoro-D-glucose (FDG) PET/MRI in thirteen patients after KTX with AKI as a functional assessment of the graft. Twenty-four healthy volunteers served as control. General kidney performance (GKP), initial flow (IF) and renal response function (RF) were calculated by standardized uptake values (SUV) and time activity curves (TAC). The GKP measured for the total kidney and medulla was significantly higher in healthy patients compared to patients after KTX (p = 0.0002 and p = 0.0004, respectively), but no difference was found for the GKP of the cortex (p = 0.59). The IF in KTX patients correlated with renal recovery, defined as change in serum creatinine 10 days after PET/MRI (r = 0.80, p = 0.001). With regard to the RF, a negative correlation for tubular damage was found (r = -0.74, p = 0.004). In conclusion, parameters obtained from FDG PET/MRI showed a possible predictive feature for renal recovery in KTX patients undergoing AKI.

Response evaluation of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus using 18F-FDG PET/MRI.

INTRODUCTION: Inhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(18F) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI. METHODS: PET FDG renal function measures such as mean transit time (MTT) and general renal performance (GRP) together with glomerular filtration rate (GFR) were determined in 20 patients with T2DM before (T2DMbaseline) and 2 weeks after initiation of therapy with SGLT2i (T2DMSGLT2i). Additionally, dynamic FDG PET data of 24 healthy subjects were used as controls. RESULTS: MTT in T2DMbaseline was significantly higher than in healthy controls (5.7 min vs 4.3 min, p=0.012) and significantly decreased to 4.4 min in T2DMSGLT2i (p=0.004). GRP of T2DMSGLT2i was higher than of T2DMbaseline (5.2 vs 4.7, p=0.02) and higher but not significantly than of healthy individuals (5.2 vs 5.1, p=0.34). Expectedly, GFR of healthy participants was significantly higher than of T2DMbaseline and T2DMSGLT2i (122 vs 92 and 86 mL/min/1.73 m², respectively; p<0.001). The higher the GRP value in kidneys of T2DMSGLT2i, the lower was the glycated hemoglobin level 3 months after therapy initiation. CONCLUSION: MTT and GRP values of patients with T2DM shifted significantly toward values of healthy control 2 weeks after therapy with SGLT2i begins. GRP in T2DMSGLT2i was associated with better long-term glycemic response 3 months after initiation of therapy. TRIAL REGISTRATION NUMBER: NCT03557138.

Comparison of different kinetic models for dynamic 18F-FDG PET/CT imaging of hepatocellular carcinoma with various, also dual-blood input function.

A kinetic modeling analysis was performed on hepatocellular carcinoma (HCC) as well as healthy liver tissue regions from dynamic FDG positron emission tomographys/computer tomography (PET/CT) cans. On basis of image derived input function from hepatic artery and portal vein, various kinetic models were compared among each other in order to check whether HCC can be classified and differ from healthy tissue within the kinetic parameters. 14 HCC and 10 healthy liver regions from FDG PET/CT scans of ten patients were analyzed from their time activity curves (TACs) were extracted from the PET dynamic images. Also the hepatic artery and the portal vein were delineated in the fused PET/CT images, which were used as input functions. Four kinetic models were applied to the TACs, using both or only one input function. Results were analyzed with several information criteria according to Akaike and Schwartz as well as be the F-Test. The paired student's t-test was used to determine the differences between HCC and healthy regions. All applied models revealed significant differences of p  < 0.01 of k 3 between HCC and healthy liver and three out of four models produced almost identical values for k 3 = 0.03 min-1 and K i = 0.03 min-1. According to the information criteria tests, a simple two-tissue model with only a venous input function is clearly preferred in case of HCC TACs. After dividing all HCC regions into two groups having a low and a high HCC-to-healthy ratio, respectively, this model also showed significant differences of k 3 between these two groups. In conclusion, results indicate that the portal vein is sufficient to describe kinetic FDG processes in HCC and healthy liver regions.

Glomerular Filtration Rate and Error Calculation Based on the Slope-Intercept Method with Chromium-51 Ethylenediaminetetraacetic Acid via a New Clinical Software: GFRcalc.

OBJECTIVE: To evaluate a home-built Java-based program (GFRcalc) to simplify the calculation of glomerular filtration rate (GFR) after administration of chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA) for routine clinical use. MATERIALS AND METHODS: In the program GFRcalc, the GFR was calculated based on the biological half-life of the 51Cr-EDTA concentration using the slope-intercept method of between two and five blood samples. Additional features included the ability to export patient data and generate clinical reports as well as to calculate the error of the fit of the GFR measurement in cases with three or more blood samples collected. The GFR was calculated from one, two and three blood samples of 133 patients with body surface-corrected GFR of 21-213 ml/min/1.73 m2. The Pearson correlation coefficient and the error of the fit for the GFR measurement were calculated for the three-sample method. RESULTS: The correlation coefficient for the three-sample method and the fit error correlated well for small fit errors; in case of fit errors >10%, the correlation coefficient partially differed in results compared to the other methods. The three-sample GFR values differed by approximately 17% from the single-sample GFRs. The fit errors of the three-sample GFRs correlated (r = 0.57) with their difference from the two-sample GFRs. CONCLUSION: In this study, the fit error that GFRcalc provided for the three-sample GFR offered a simple and reliable method to check the results obtained. This could also allow physicians to assess the reliability of the results and base their decisions on the quality of the measurement.

WWSSF - a worldwide study on radioisotopic renal split function: reproducibility of renal split function assessment in children.

PURPOSE: The split or differential renal function is the most widely accepted quantitative parameter derived from radionuclide renography. To examine the intercenter variance of this parameter, we designed a worldwide round robin test. METHODS: Five selected dynamic renal studies have been distributed all over the world by e-mail. Three of these studies are anonymized patient data acquired using the EANM standardized protocol and two studies are phantom studies. In a simple form, individual participants were asked to measure renal split function as well as to provide additional information such as data analysis software, positioning of background region of interest, or the method of calculation. RESULTS: We received the evaluation forms from 34 centers located in 21 countries. The analysis of the round robin test yielded an overall z-score of 0.3 (a z-score below 1 reflecting a good result). However, the z-scores from several centers were unacceptably high, with values greater than 3. In particular, the studies with impaired renal function showed a wide variance. CONCLUSION: A wide variance in the split renal function was found in patients with impaired kidney function. This study indicates the ultimate importance of quality control and standardization of the measurement of the split renal function. It is especially important with respect to the commonly accepted threshold for significant change in split renal function by 10%.