The conundrum of high-grade hydronephrosis with non-obstructive drainage on diuretic renography.

BACKGROUND: Patients with high grade hydronephrosis (HN) and non-obstructive drainage on mercaptoacetyltriglycine (MAG-3) diuretic renography (renal scans) can pose a dilemma for clinicians. Some patients may progress and require pyeloplasty; however, more clarity is needed on outcomes among these patients. OBJECTIVE: Our primary objective was to predict which patients with high-grade HN and non-obstructive renal scan, (defined as T ½ time <20 min) would experience resolution of HN. Our secondary objective was to determine predictors for surgical intervention. STUDY DESIGN: Patients with prenatally detected HN were prospectively enrolled from 7 centers from 2007 to 2022. Included patients had a renal scan with T ½<20 min and Society for Fetal Urology (SFU) grade 3 or 4 at last ultrasound (RBUS) prior to renal scan. Primary outcome was resolution of HN defined as SFU grade 1 and anterior posterior diameter of the renal pelvis (APD) < 10 mm on follow-up RBUS. Secondary outcome was pyeloplasty, comparing patients undergoing pyeloplasty with patients followed with serial imaging without resolution. Multivariable logistic regression was used for analysis. RESULTS: Of the total 2228 patients, 1311 had isolated HN, 338 patients had a renal scan and 129 met inclusion criteria. Median age at renal scan was 3.1 months, 77% were male and median follow-up was 35 months (IQR 20-49). We found that 22% (29/129) resolved, 42% of patients had pyeloplasty (54/129) and 36% had persistent HN that required follow-up (46/129). Univariate predictors of resolution were age≥3 months at time of renal scan (p = 0.05), T ½ time≤5 min (p = 0.09), SFU grade 3 (p = 0.0009), and APD<20 mm (p = 0.005). Upon multivariable analysis, SFU grade 3 (OR = 4.14, 95% CI: 1.30-13.4, p = 0.02) and APD<20 mm (OR = 6.62, 95% CI: 1.41-31.0, p = 0.02) were significant predictors of resolution. In the analysis of decision for pyeloplasty, SFU grade 4 (OR = 2.40, 95% CI: 1.01-5.71, p = 0.04) and T ½ time on subsequent renal scan of ≥20 min (OR = 5.14, 95% CI: 1.54-17.1, p = 0.008) were the significant predictors. CONCLUSIONS: Patients with high grade HN and reassuring renal scan can pose a significant challenge to clinical management. Our results help identify a specific candidate for observation with little risk for progression: the patient with SFU grade 3, APD under 20 mm, T ½ of 5 min or less who was 3 months or older at the time of renal scan. However, many patients may progress to surgery or do not fully resolve and require continued follow-up.

Noninvasive measurement of tracer extraction efficiency in tissue, illustrated with Tc-99m-MAG3.

OBJECTIVE: The aim of this study is to develop a noninvasive technique for measuring tissue tracer extraction efficiency ( E ) and illustrate it for Tc-99m-mercaptoacetyltriglycine (MAG3) and kidney. METHODS: E was measured in 10 patients with normal MAG3 renography. E is the ratio of tissue clearance-to-blood flow ( Ki/F ). For single-photon tracers, attenuation constants are unknown, so Ki and F cannot be separately measured. However, by deriving attenuation-uncorrected Ki' and F' from the same regions of interests (ROIs), these constants cancel out, giving E . Using a lung ROI for blood activity, F was measured from first-pass and Ki' from Gjedde-Patlak-Rutland (GPR) analysis up to 130 s. Because of interference from right ventricle, a left ventricular ROI (LV) is unsuitable for F' but was used in GPR analysis, making an adjustment for the ratio of respective blood pool signals arising from lung and LV ROIs in early frames (60-90 s). RESULTS: A lung ROI underestimates F' by 4% at normal LV function. Chest wall interstitial activity ( I ), which does not affect F' , amounted to 53 and 30% of the lung and LV signals at 20 min, and 12 and 6% at 130 s, resulting in underestimations of Ki of 4 and 2%, respectively. Ignoring these opposing errors, E based on lung ROI for left and right kidneys was 43.5 (SD 8)% and 47.3 (9)%, and based on LV ROI for GPR analysis was 44.5 (10.9)% and 48.3 (10.6)%. CONCLUSION: E can be measured by combining blood flow from first-pass with clearance from GPR analysis, and has potential value both clinically and in clinical research.

Kidney dynamic SPECT acquisition on a CZT swiveling-detector ring camera: an in vivo pilot study.

BACKGROUND: Large field of view CZT SPECT cameras with a ring geometry are available for some years now. Thanks to their good sensitivity and high temporal resolution, general dynamic SPECT imaging may be performed more easily, without resorting to dedicated systems. To evaluate the dynamic SPECT imaging by such cameras, we have performed an in vivo pilot study to analyze the kidney function of a pig and compare the results to standard dynamic planar imaging by a conventional gamma camera. METHODS: A 7-week-old (12 kg) female Landrace pig was injected with [99mTc]Tc-MAG3 and a 30 min dynamic SPECT acquisition of the kidneys was performed on a CZT ring camera. A fast SPECT/CT was acquired with the same camera immediately after the dynamic SPECT, without moving the pig, and used for attenuation correction and drawing regions of interest. The next day the same pig underwent a dynamic planar imaging of the kidneys by a conventional 2-head gamma camera. The dynamic SPECT acquisition was reconstructed using a MLEM algorithm with up to 20 iterations, with and without attenuation correction. Time-activity curves of the total counts of each kidney were extracted from 2D and 3D dynamic images. An adapted 2-compartment model was derived to fit the data points and extract physiological parameters. Comparison of these parameters was performed between the different reconstructions and acquisitions. RESULTS: Time-activity curves were nicely fitted with the 2-compartment model taking into account the anesthesia and bladder filling. Kidney physiological parameters were found in agreement with literature values. Good agreement of these parameters was obtained for the right kidney between dynamic SPECT and planar imaging. Regional analysis of the kidneys can be performed in the case of the dynamic SPECT imaging and provided good agreement with the whole kidney results. CONCLUSIONS: Dynamic SPECT imaging is feasible with CZT swiveling-detector ring cameras and provides results in agreement with dynamic planar imaging by conventional gamma cameras. Regional analysis of organs uptake and clearance becomes possible. Further studies are required regarding the optimization of acquisition and reconstruction parameters to improve image quality and enable absolute quantification.

Comparison of absolute renal uptake by using Tc-99m MAG-3 and Tc-99m DMSA.

PURPOSE: The purpose of this study is to compare the value of absolute renal uptake (ARU %) in patients by using Tc-99m MAG-3 and Tc-99m DMSA scan. MATERIAL AND METHODS: Absolute renal uptake is calculated using Tc-99m MAG-3 and Tc-99m DMSA in renal scintigraphy, Itoh and Tauex kidney depth methods used, respectively. n = 40 adult patients of both genders were included. All patients underwent Tc-99m MAG-3 and Tc-99m DMSA, respectively. RESULTS: The values of ARU (%) were calculated separately in selected patients n = 40, (left = 17, right = 23 normal functioning kidneys) by MAG-3 and DMSA. Absolute renal uptake (%) of Tc-99m MAG-3 in left kidneys was found to be 15.2 ±â€…3.4, with spilt renal function 79.2 ±â€…14.7 and ARU (%) in right kidneys 16.2 ±â€…3.4 with spilt renal function 77.5 ±â€…19. Absolute renal uptake of Tc-99m DMSA in left kidneys was 17.5 ±â€…3.2 and in right kidneys 17.9 ±â€…4.5 with spilt renal function 81.8 ±â€…10.7 and 79.3 ±â€…13.8 for left and right kidney, respectively. Statistical analysis showed strong Pearson correlation. CONCLUSION: Absolute renal uptake % was found to be more reliable in cases of bilateral compromised kidneys. ARU (%) calculated by Tc-99m MAG-3 solely can be used as predictor of renal function. The use of Tc-99m MAG-3 has more advantages than Tc-99m DMSA alone in renal scintigraphy as dynamic scintigraphy gives less radiation burden to patient, more information regarding renal function, and shorter stay time at hospital in comparison to static renal imaging. SRF % is less reliable than ARU (%).

Maximal detrusor pressure can be predicted using technetium-99m-mertcaptoacetyltriglycine renal scintigraphy in the early stages of spinal cord injury.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the potential of technetium-99m-mercaptoacetyltriglycine (99mTc-MAG-3) renal scintigraphy for predicting maximal detrusor pressure in the early stages of spinal cord injury (SCI). SETTING: Tertiary rehabilitation facility. METHODS: Medical records of individuals with SCI admitted between January 2020 and April 2023 who underwent both 99mTc-MAG-3 renal scintigraphy and urodynamic study within 90 days of SCI onset were retrospectively reviewed. Pearson's coefficient analysis was performed to determine the relationship between 99mTc-MAG-3 renal scintigraphy findings and urodynamic study findings. A multivariate linear regression analysis was performed to determine the best predictors of maximal detrusor pressure. A multivariate logistic regression analysis was performed to determine risk factors for high detrusor pressure. RESULTS: Ninety-four participants were enrolled in this study. Pearson's correlation analysis showed that effective renal plasma flow (ERPF) and ERPF (% predicted) were significantly correlated with maximal detrusor pressure. The multivariate linear regression analysis demonstrated that ERPF (% predicted) was a significant predictor of maximal detrusor pressure. The multivariate logistic regression analysis showed that ERPF (% predicted) was significantly associated with high detrusor pressure. The receiver operating characteristic curve demonstrated that the predictive model had an area under the curve of 0.725, with an ERPF (% predicted) cut-off of 64.05%, sensitivity 1.000, and specificity 0.429. CONCLUSIONS: These results suggest that 99mTc-MAG-3 renal scintigraphy may be useful for predicting high detrusor pressure in early SCI and may guide the timing of urodynamic studies in individuals with early SCI for appropriate management of neurogenic lower urinary tract dysfunction.

Assessment of infant gonadal dose irradiated from urine-contaminated diapers during diuretic renal scintigraphy.

OBJECTIVE: To estimate the gonadal doses irradiated from urine- contaminated diapers during diuretic renal scintigraphy. METHODS: Images of 31 patients (18 males and 13 females) with urine-contaminated diapers during 99m Tc-MAG3 renal scintigraphy were analyzed. The count rate of the diapers was converted into a time-activity curve based on the calibrated factor of the gamma camera system. The cumulative activity was determined from the area under the curve. By incorporating dose per unit cumulative activity pre-calculated from Monte Carlo simulation with 0-year phantom, the gonadal dose irradiated from diaper was calculated. To assess the degree of this additionally introduced dose from diapers, the calculated gonadal dose was compared to the internal gonadal dose from injected radiotracer activity. RESULTS: The cumulative activities irradiated from urine-contaminated diapers were 1.12 E04 ±â€…1.29E04 MBq.s in male infants, which was nearly half of the 1.94 E04 ±â€…1.80E04 MBq.s ( P  = 0.15) in female infants. However, the absorbed doses for testes in male infants were 7.37E-01 ±â€…8.50E-01 mGy, which was approximately 10 times the 6.38E-02 ±â€…5.94E-02 mGy for ovaries in female infants ( P  < 0.01). The diaper-introduced dose for testes and ovaries was 91.7% and 3.9% of the gonadal doses from the injected activity in patients with normal renal function, and 99.0% and 4.3% of those in patients with abnormal renal function. CONCLUSION: Urine-contaminated diapers introduced additional radiation doses to infant patients during 99m Tc-MAG3 renal scintigraphy. The gonadal doses were of significance in male infants who had nearly double the absorbed dose for the testes.

Preclinical Evaluation of 99mTc-MAG3-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with 99mTc-MAG3-5-F(ab')2.

Triggering receptor expressed on myeloid cells-2 (TREM2), which is expressed on the surface of tumor-associated macrophages (TAMs), has been found to play a major role in the diagnosis and treatment of tumors. TREM2 expression is significantly upregulated in tumor tissues, and therefore, targeting TREM2 for tumor imaging may be of value. Previously, we performed TREM2 targeting imaging by using 68Ga-NOTA-COG1410 or a 124I-labeled monoclonal antibody (mAb) and F(ab')2 in mouse models of colon and gastric tumors. However, some of the shortcomings of these probes (i.e., the high uptake of 68Ga-NOTA-COG1410 in the liver, the difficulty of obtaining iodine-124, and the long half-life of iodine-124) have hindered their clinical use. Herein, we sought to synthesize novel molecular probes targeting TREM2 that are more conducive to clinical translation, eliminating the interference of isotope availability and in vivo probe biodistribution issues. Therefore, we established A549 cell lines with negative human TREM2 (hTREM2) expression (GFP tag; hTREM2- A549) or upregulated hTREM2 expression (GFP tag; hTREM2+ A549) using lentiviral transfection and confirmed these with Western blotting and immunocytochemistry. We then prepared a mouse anti-human TREM2 (5-mAb) by immunizing with the hTREM2 antigen. The antibody fragments 5-F(ab')2 and 5-Fab were prepared from 5-mAb, and 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab were then synthesized with excellent stability and specificity. 99mTc-MAG3-5-F(ab')2 had a slightly higher in vitro affinity than 99mTc-MAG3-5-Fab (Kd = 3.32 ± 0.05 nmol versus 4.62 ± 0.85 nmol). 99mTc-MAG3-5-F(ab')2 and 99mTc-MAG3-5-Fab both showed excellent specificity: after adding a 100-fold precursor, the two probes binding to the cells were almost blocked. In vivo pharmacokinetics showed that the distribution and elimination half-lives of 99mTc-MAG3-5-Fab (T1/2α = 1.25 ± 0.30 min and T1/2ß = 21.98 ± 2.80 min, respectively) were significantly reduced compared to those of 99mTc-MAG3-5-F(ab')2 (T1/2α = 2.64 ± 0.37 min and T1/2ß = 86.55 ± 26.86 min, respectively). In micro single-photon emission computed tomography/computed tomography (micro-SPECT/CT) imaging, the tumor was clearly displayed at 1 h after 99mTc-MAG3-5-Fab injection, while the blood background was extremely low at 3 h, and the probe was mainly excreted through the kidneys and biliary tract. 99mTc-MAG3-5-F(ab')2 uptake was also detected at the tumor site, although the blood background was consistently high. The biodistribution results were consistent with the micro-SPECT/CT imaging results. 99mTc-MAG3-5-Fab could clearly display hTREM2+ A549 tumors in a short time (1 h) with low uptake in nontumor organs and tissues and thus has clinical application prospects.

Determination of tissue tracer transit of Technetium-99m-mercaptoacetyltriglycine diuretic renography in infants with suspected ureteropelvic junction obstruction - A multicenter prospective observational study.

INTRODUCTION: There is an ongoing controversy regarding management of ureteropelvic junction obstruction in infants, with a shift towards a non-operative approach. However, precise predictors of outcome are lacking. Recent studies postulated a high prognostic value of Technetium-99m-mercaptoacetyltriglycine tissue tracer transit with regard to the development of an impaired differential renal function and its potential improvement following pyeloplasty. OBJECTIVE: To evaluate the prognostic value of Technetium-99m-mercaptoacetyltriglycine tissue tracer transit for the occurrence of changes in differential renal function in infants with suspected unilateral ureteropelvic junction obstruction in a prospective observational multicenter study. STUDY DESIGN: Infants below 3 months of age with a unilateral isolated hydronephrosis ≥ grade 3 received ultrasound and Technetium-99m-mercaptoacetyltriglycine diuretic renography at two different time points (timepoint 1 and timepoint 2). Data were analyzed at local centers and at the study center and were collected in an internet-based database system. Tissue tracer transit was determined for each diuretic renography, inter-observer variation for tissue tracer transit and standard parameters for judgement of differential renal function development were assessed. RESULTS: Thirty-seven patients were analyzed. Median age was 11 weeks (7-15) at timepoint 1 and 26 weeks (19-33) at timepoint 2. A delayed tissue tracer transit at timepoint 1 was not associated with deterioration of differential renal function at timepoint 2 in both, locally (10/37 cases) and centrally (4/37) analyzed cases. However, sensitivity and specificity were poor. The intraclass correlation coefficient comparing local and central findings of tissue tracer transit and renal drainage demonstrated poor or fair agreement. Analysis of standard parameters for differential renal function development revealed a prognostic value only for the dichotomized anteroposterior renal pelvic diameter (APD, p = 0.03, 95%-CI 1.2-22.2). DISCUSSION: Regarding the primary endpoint of our study, we could not confirm the hypothesis that delayed tissue tracer transit reliably predicts a subsequent decline in differential renal function in the cohort of patients studied. Whether the low age of the patients, technical problems in the correct assessment of tissue tracer transit by the investigator in early infancy, the study design, or the parameter itself played a role is debated. CONCLUSION: In the presented setting tissue tracer transit was not useful as a predictive parameter for deterioration of differential renal function in infants with suspected unilateral ureteropelvic junction obstruction. Sensitivity and specificity of tissue tracer transit were not sufficient for risk stratification. Improved utility of tissue tracer transit as a marker might be achieved using a different study setting.

Computer assisted interpretation of Tc-99m mercaptoacetyltriglycine diuretic scintigraphy enhances resident performance.

OBJECTIVE: iRENEX is a software module that incorporates scintigraphic and clinical data to interpret 99m Tc- mercaptoacetyltriglycine (MAG3) diuretic studies and provide reasons for their conclusions. Our objectives were to compare iRENEX interpretations with those of expert physicians, use iRENEX to evaluate resident performance and determine if iRENEX could improve the diagnostic accuracy of experienced residents. METHODS: Baseline and furosemide 99m Tc-MAG3 acquisitions of 50 patients with suspected obstruction (mean age ± SD, 58.7 ±â€…15.8 years, 60% female) were randomly selected from an archived database and independently interpreted by iRENEX, three expert readers and four nuclear medicine residents with one full year of residency. All raters had access to scintigraphic data and a text file containing clinical information and scored each kidney on a scale from +1.0 to -1.0. Scores ≥0.20 represented obstruction with higher scores indicating greater confidence. Scores +0.19 to -0.19 were indeterminate; scores ≤-0.20 indicated no obstruction. Several months later, residents reinterpreted the studies with access to iRENEX. Receiver operating characteristic (ROC) analysis and concordance correlation coefficient (CCC) quantified agreement. RESULTS: The CCC among experts was higher than that among residents, 0.84, versus 0.39, respectively, P  < 0.001. When residents reinterpreted the studies with iRENEX, their CCC improved from 0.39 to 0.73, P  < 0.001. ROC analysis showed significant improvement in the ability of residents to distinguish between obstructed and non-obstructed kidneys using iRENEX ( P  = 0.036). CONCLUSION: iRENEX interpretations were comparable to those of experts. iRENEX reduced interobserver variability among experienced residents and led to better agreement between resident and expert interpretations.

Transferability of a two-strip method for the quality control of technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3).

OBJECTIVES: Technetium-99m mercapto-acetyl-triglycine ([99mTc]Tc-MAG3) is a radiopharmaceutical diagnostic agent used in nuclear medicine intended for the exploration of nephrological and urological disorders. Patient safety and reliability of this imaging procedure especially depend on the radiochemical purity (RCP) of the [99mTc]Tc-MAG3 preparation. Recently, the Summary of Product Characteristics (SPC) of NephroMAG, a kit dedicated to [99mTc]Tc-MAG3 preparation, proposed a two-strip thin layer chromatography (TLC) based quality control (QC) method. Also, Straub et al recently proposed another TLC based QC method. We sought to evaluate the transferability of these QC methods in our hospital radiopharmacy and compared them to our currently employed TLC method and radio-HPLC (high-pressure liquid chromatography) to select the most appropriate in the context of hospital radiopharmacy. METHODS: Ten consecutive [99mTc]Tc-MAG3 preparations were controlled using: HPLC combined with a radiodetector (radio-HPLC), a single strip TLC method (method 1) in current use in our centre, a two-strip TLC method described in the SPC (method SPC) and a two-strip TLC method (method 2) described by Straub et al. Quantitative results for the four tested QC methods were measured and compared in terms of RCP (%), sodium pertechnetate ([99mTc]TcO4 -) (%) and duration of analysis (min). RESULTS: RCP was significantly different between method SPC and radio-HPLC (p<0.001) and method 2 (p<0.001). Also, the percentage of [99mTc]TcO4 - was statistically different between the radio-HPLC and the method SPC (p<0.001), but not with the method 1 and method 2 group (p>0.05). The duration of analysis (min) was significantly different between the four QC procedures (p<0.001) with method 2 and method SPC being the quickest. CONCLUSIONS: Our study showed it is possible to transfer and select a quick and reliable QC method for the preparation of NephroMAG kits in our centre. We therefore advise the widespread use of the method from Straub et al in hospital radiopharmacies.

Assessment of Individual Renal Function Using 99mTc-MAG3 Renography.

BACKGROUND/AIM: This study performed 99mTc-MAG3 renal scintigraphy on rabbit kidneys and evaluated its ability to identify obstructive or non-obstructive kidneys. MATERIALS AND METHODS: Renal function was assessed during a four-week post-obstruction period by obtaining planar images of 99mTc-MAG3 activity following an ear vein injection. The individual renal function was evaluated by renal scintigraphy in conjunction with histopathological and morphological examinations. RESULTS: The renal perfusion of 99mTc-MAG3 in the right kidney with a ureteral obstruction decreased with time. The width, height, and cortical thickness of the obstructed right kidney were significantly larger than those of the left kidney. A histopathological examination four weeks after the ureteral obstruction revealed a typical pattern of urinary tract obstruction, including multiple tubules, enlargement of the interstitial area, and cytoplasmic vacuoles. CONCLUSION: 99mTc-MAG3 renal scintigraphy provides the kidney shape and size and can identify potential obstructive and non-obstructive kidneys in rabbits.

Development and autoregulation of kidney function in children: a retrospective study using 99mTc-MAG3 renography.

BACKGROUND: Both the development of kidney function in healthy children and autoregulation ability of kidney function in patients with asymmetric kidneys are important in clinical diagnosis and treatment of kidney-related diseases, but there are however only limited studies. This study aimed to investigate development of kidney function in normal children with healthy symmetric kidneys and autoregulation of the healthy kidney compensating the functional loss of a diseased one in children with asymmetric kidneys. METHODS: Two hundred thirty-seven children (156 male, 81 female) from 0 to 20y (average 4.6y ± 5.1) undergoing 99mTc-MAG3 renography were included, comprising 134 with healthy symmetrically functioning kidneys and 103 with asymmetric kidneys. Clearance was calculated from kidney uptakes at 1-2 min. A developmental model between MAG3 clearance (CL) and patient age in normal group was identified (CL = 84.39Age0.395 ml/min, r = 0.957, p < 0.001). The clearance autoregulation rate in abnormal group with asymmetric kidneys was defined as the ratio of the measured MAG3 clearance and the normal value predicted from the renal developmental model of normal group. RESULTS: No significant difference of MAG3 clearance (p = 0.723) was found between independent abnormal group and normal group. The autoregulation rate of kidney clearance in abnormal group was 94.2% on average, and no significant differences were found between two age groups (p = 0.49), male and female (p = 0.39), and left kidney and right kidney (p = 0.92) but two different grades of asymmetric kidneys (p = 0.02). CONCLUSIONS: The healthy kidney of two asymmetric kidneys can automatically regulate total kidney function up to 94% of two symmetric kidneys in normal children.

Technetium-99m-MAG3 and technetium-99m-DTPA: Renal clearance measured by the constant infusion technique - Old news?

BACKGROUND: Accurate, precise and straightforward methods for measuring glomerular filtration rate (GFR) and/or renal plasma flow (RPF) are still in demand today. The time-consuming constant infusion technique (CIT) is the gold standard and preferred for research, whereas the simple, but less precise, single injection technique (SIT) is used in clinical settings. This study investigated the use of 99m Tc-DTPA and 99m Tc-MAG3 by CIT as a measure of renal function. We developed and evaluated a model to balance the primer dose and infusion rate in an attempt to obtain plasma steady state as quickly as possible. METHODS: 14 healthy subjects received 99m Tc-DTPA and 6 hypertensive patients received 99m Tc-MAG3 in a standardized protocol. All participants had an eGFR above 60 ml/min and none had fluid retention. An intravenous primer injection of the relevant tracer was followed by a sustained infusion over 4.5 h with the same radiopharmaceutical. Blood and urine samples were collected at fixed intervals. RESULTS: 99m Tc-DTPA clearance reached steady state after 210 min (plasma clearance 78 ± 18 ml/min, urine clearance 110 ± 28 ml/min), whereas 99m Tc-MAG3  clearance achieved steady state after 150 min (plasma clearance 212 ± 56 ml/min, urine clearance 233 ± 59 ml/min). CONCLUSION: Constant infusion technique with fixed primer and infusion rate using 99m Tc-MAG3 is feasible for research purposes. The longer time for reaching plasma steady state using 99m Tc-DTPA makes CIT with this tracer less optimal. If the primer/sustained balance can be optimized, for example using a priori SIT information, 99m Tc-DTPA as tracer for CIT may also be feasible.

A gravity-assisted approach to the management of urinary diversion: 99mTc-MAG3 diuresis renography with F + 10(sp) method.

OBJECTIVE: Radical cystectomy with permanent urinary diversion is the gold standard treatment for invasive muscle bladder cancer. Hydronephrosis is common in these patients, but Ultrasound (US) or Computed Tomography Urography (CTU) scan are unable to discriminate obstructive from non-obstructive hydronephrosis. We used Diuresis Renography (DR) with F + 10 in seated position (sp) method in the identification of patients with a Uretero-ileal Anastomosis Stricture (UAS) who would benefit from surgical therapy. METHODS: We studied 39 asymptomatic patients, who underwent radical cystectomy and urinary diversion. Based on radiological findings (US, CTU) 44 kidneys were hydronephrotic. All patients underwent a 99mTc-MAG3 DR with F + 10(sp) method. We acquired a DR for 20 min with the patient in a seated position. Patient drank 400-500 mL of water at 5 min after tracer injection and received a 20 mg bolus of Furosemide at 10 min during dynamic acquisition. The indices Time to peak, diuretic half time, and 20 min/peak ratio have been evaluated. Retrograde pyelography confirmed UAS in all patients with DR obstructive findings. We repeated DR as follow-up in two subgroups of patients. RESULTS: DR with F + 10(sp) method showed obstructive findings in 36 out of 44 hydronephrotic kidneys. 6 patients showed non-obstructive findings. 32 patients showed obstructive findings (20 out of 32 developed UAS within 12 months after surgery). Fifteen pts underwent a surgical treatment of UAS. In 1 patient with equivocal findings, we observed an ileo-ureteral reflux. CONCLUSIONS: The DR with F + 10(sp) method in the seated position has a lower uncertain diagnostic rate, compared to the radiological findings of US or CTU, in management of bladder cancer patients with urinary diversion. The semiquantitative indices diuretic half time and 20 min/peak ratio evaluated in a condition of favorable gravity reduce uncertain responses improving interobserver concordance.

U.S. Diagnostic Reference Levels and Achievable Administered Activities for Adult Renal Scintigraphy: An Analysis of the Intersocietal Accreditation Committee Nuclear Laboratories.

The goal of this work was to determine U.S. diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for adult renal scintigraphy. Methods: Under an Institutional Review Board-approved protocol, data were collected from the Intersocietal Accreditation Commission during one 3-y accreditation cycle encompassing 110 facilities. Elements included radiopharmaceutical, administered activity, practice type, and examination volume. DRLs and AAAs were calculated and compared with non-U.S. values and societal recommendations as available. Results: Ninety-three facilities provided data on 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), and 15 provided data on 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) for adult renal scintigraphy exams. Analysis demonstrated a DRL of 392.2 MBq (10.6 mCi) for 99mTc-MAG3 and 531.7 MBq (14.4 mCi) for 99mTc-DTPA, with an AAA of 370 MBq (10 mCi) for 99mTc-MAG3 and 445.9 MBq (12.1 mCi) for 99mTc-DTPA. Conclusion: The resultant calculated novel U.S. DRLs and AAAs may serve as benchmarks that nuclear medicine facilities may use to refine renal scintigraphy protocols, reduce patient doses, and potentially guide future societal guideline recommendations.

Renogram image characteristics and the reproducibility of differential renal function measurement.

PURPOSE: Patient factors such as age and glomerular filtration rate (GFR), have been implicated as causes for poor reproducibility of differential renal function (DRF) estimates on 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renography. This study aims to investigate factors associated with the reproducibility of DRF measurements. METHODS: The association between age, GFR and imaged derived image characteristics and reproducibility of repeated DRF estimates calculated using the area under the curve method and the Rutland Patlak method was analysed for cohort 1 (n = 127). The association between these variables and reproducibility of DRF was tested with univariate linear regression. The univariate linear regression results were used to plan the multiple linear regression combinations.The associations between variables identified and reproducibility of DRF values were then tested in a second cohort (n = 227). RESULTS: The R2 values for goodness-to-fit for the multiple regression models ranged from 0.33 to 0.49 for cohort 1 and from 0.17 to 0.22 for cohort 2. Left kidney to background ratio (LKTBR) was significant in all the multiple linear regression combinations (P < 0.05). Right kidney to background ratio (RKTBR), right renal margins well defined, right renal margins poorly visualised, time visualisation right calyces and age were significant in most combinations. The reproducibility of DRF measurement was decreased when the kidney to background ratio (KTBR) was ≤2. CONCLUSION: Only LKTBR, RKTBR, right renal margins well defined, time visualisation right calyces and age predicted reproducibility for the measurement of DRF on 99mTc-MAG3 renograms. The KTBR should be incorporated into the renal processing software as a quality control step. The DRF values should be interpreted with caution if the KTBR is ≤2.0.

Advantages of gravity-assisted diuretic renogram: F + 10 (seated position) method.

INTRODUCTION: In 1978, O'Reilly introduced the diuretic renogram using the F + 20 method. Initially, the patient was examined in the seated position. A dose of 40 mg furosemide was injected intravenously 20 min following tracer injection and dynamic acquisition was prolonged for 15-20 min. In 1992, the guidelines suggested to study patients in the supine position to avoid risk of diuretic-induced hypotension and reduce patient movement. Unfortunately, equivocal findings were reported in 15-30% of cases. Side effects such as bladder fullness and disruption because of voiding were reported. Several methods had been proposed in the supine position, such as the well-tempered diuretic renogram F + 20, F - 15, F0 and F + 2, with different time in minute of diuretic administration in relation to tracer injection. However, as confirmed by many studies, there was no clear evidence suggesting superiority among these methods. We suggest using the diuretic renogram with the F ± 10(sp) method for the diagnosis of obstruction in adult patients with hydronephrosis and for the follow-up in patients who underwent a surgical treatment of the urinary tract. METHODS: We searched all international guidelines and articles of most influential authors published from 1978 to October 2020 on diuretic renogram. RESULTS: We selected 60 articles. DISCUSSION: F + 10(sp) method improves patient compliance avoiding bladder fullness-related problems, without need of catheterization. It allows for a more reliable quantification of the renal output, thanks to outflow indices that are favored by gravity effects.

177Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α1-Microglobulin (A1M), Including Kidney Damage Assessment Using 99mTc-MAG3 Imaging.

Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α1-microglobulin (A1M) together with 177-Lutetium (177Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity. Nude mice with subcutaneous LNCaP xenografts were injected with 50 or 100 MBq of [177Lu]Lu-PSMA-617, with or without injections of recombinant A1M (rA1M) (at T = 0 and T = 24 h). Kidney absorbed dose was calculated to 7.36 Gy at 4 days post a 100 MBq injection. Activity distribution was imaged with Single-Photon Emission Computed Tomography (SPECT) at 24 h. Tumor volumes were measured continuously, and kidneys and blood were collected at termination (3-4 days and 3-4 weeks after injections). In a parallel set of experiments, mice were given [177Lu]Lu-PSMA-617 and rA1M as above and dynamic technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3) SPECT imaging was performed prior to injection, and 3- and 6-months post injection. Blood and urine were continuously sampled. At termination (6 months) the kidneys were resected. Biomarkers of kidney function, expression of stress genes and kidney histopathology were analyzed. [177Lu]Lu-PSMA-617 uptake, in tumors and kidneys, as well as treatment efficacy did not differ between rA1M and vehicle groups. In mice given rA1M, [99mTc]Tc-MAG3 imaging revealed a significantly higher slope of initial uptake at three months compared to mice co-injected with [177Lu]Lu-PSMA-617 and vehicle. Little or no change compared to control was seen in urine albumin, serum/plasma urea levels, RT-qPCR analysis of stress response genes and in the kidney histopathological evaluation. In conclusion, [99mTc]Tc-MAG3 imaging presented itself as a sensitive tool to detect changes in kidney function revealing that administration of rA1M has a potentially positive effect on kidney perfusion and tubular function when combined with [177Lu]Lu-PSMA-617 therapy. Furthermore, we could show that rA1M did not affect anti-PSMA radioligand therapy efficacy.