Optimizing PSMA scintigraphy for resource limited settings - a retrospective comparative study.

BACKGROUND: PSMA PET/CT is the most sensitive molecular imaging modality for prostate cancer (PCa), yet much of the developing world has little or no access to PET/CT. [99mTc]Tc-PSMA scintigraphy (PS) is a cheaper and more accessible gamma camera-based alternative. However, many resource-constrained departments have only a single camera without tomographic or hybrid imaging functionality, and camera time is frequently in high demand. Simplifying imaging protocols by limiting the field of view (FOV) and omitting SPECT/CT or even SPECT may provide a partial solution. The aim was thus to determine the adequacy of PS planar-only and/or SPECT-only imaging protocols with a limited FOV. METHODS: The scans of 95 patients with histologically proven PCa who underwent PS with full-body planar and multi-FOV SPECT/CT were reviewed. The detection rates for uptake in the prostate gland/bed and in metastases were compared on planar, SPECT, and SPECT/CT. The agreement between modalities was calculated for the detection of metastases and for staging. The impact of imaging a limited FOV was determined. RESULTS: Pathological prostatic uptake was seen in all cases on SPECT/CT (excluding two post-prostatectomy patients), 90.3% of cases on SPECT, and 15.1% on planar images (p < 0.001). Eleven (11.7%) patients had seminal vesicle involvement on SPECT/CT, which was undetectable/indistinguishable on planar images and SPECT. The agreement between modalities was moderate to good (κ = 0.41 to 0.61) for the detection of nodal metastases, with detection rates that did not differ significantly (SPECT/CT = 11.6%, SPECT = 8.4%, planar = 5.3%). Detection rates for bone metastases were 14.7% (SPECT/CT) and 11.6% (SPECT and planar). Agreement between modalities for the detection of bone metastases was good (κ = 0.73 to 0.77). Three (3.1%) patients had visceral metastases on SPECT/CT, two of which were detected on SPECT and planar. There was good agreement between modalities for the TNM staging of patients (κ = 0.70 to 0.88). No metastatic lesions were missed on the limited FOV images. CONCLUSION: When PS scintigraphy is performed, SPECT/CT is recommended. However, the lack of SPECT/CT capabilities should not preclude the use of PS in the presence of limited resources, as both planar and SPECT imaging are adequate and will correctly stage most PCa patients. Furthermore, time-based optimisations are achievable by limiting the FOV to exclude the distal lower limbs.

Measurement of Glomerular Filtration Rate.

Glomerular filtration rate (GFR) can be estimated from the plasma concentration of endogenous substances such as creatinine, and it is simple and cost-effective to do so, but the error on these estimates on an individual patient basis is high. Thus, GFR measurement is indicated in any clinical situation in which greater accuracy is required especially if the result will impact treatment decisions. Outside of the United States the radiopharmaceutical that has been most commonly used for measurement of GFR is 51Cr-EDTA. However, due to a recent reduction in supply, there has been a shift to 99mTc-DTPA. The differences in clearance between these two tracers are small, and their clearance is comparable to the non-radiopharmaceutical markers inulin, iohexol and iothalamate. A few PET GFR tracers are currently under investigation for clinical use. Measurement of the urinary clearance of a tracer is the historical gold standard technique, however this method is prone to error due to difficulties with urine collection and inaccuracies associated with measuring residual activity in the bladder and renal drainage systems. Plasma clearance techniques provide a more practical and robust alternative and have good precision despite overestimating GFR slightly. Measurement of the area under the full plasma clearance curve is the reference method but due to the large number of blood samples required, it is largely limited to research settings. The slope-intercept and single-sample methods are simpler yet accurate alternatives that can be used in most patients. However, in patients with expanded third spaces or very low GFR (<25 mL/min/1.73 m2), different calculation methods are used that require blood sampling up to 24 hours. Camera-based methods are currently not recommended due to their imprecision. For the purposes of interpreting a GFR result, reliable reference data is available for adults and children, mostly derived from 51Cr-EDTA clearance measurements, but applicable to 99mTc-DTPA GFR. GFR has notable biological variation and is susceptible to measurement errors, the combination of which translates into a high coefficient of variation for repeat measurements. Consequently, when serial measurements are performed, large changes (>20%) are required before a change can be regarded as significant. While biological variation is largely fixed, measurement errors can be minimized through careful work in combination with a system of thorough quality control checks.

Repeatability of glomerular filtration rate studies performed using 99mTc-DTPA in a population including cancer patients.

OBJECTIVE: Glomerular filtration rate (GFR) measurement remains an integral investigation in clinical practice and is particularly important in the prediction and follow-up of renal side-effects of nephrotoxic chemotherapy in cancer patients. Knowing the coefficient of variation (CV) of a test is vital for the correct interpretation of serial studies. Recent difficulties with 51Cr-EDTA availability have renewed interest in 99mTc-DTPA, but there is a paucity of data on the test-retest variability of this radiopharmaceutical. Furthermore, the authors are unaware of published repeatability data in cancer patients. The aim of this study was to determine the CV of repeat 99mTc-DTPA GFR measurements in a clinical patient population that included cancer patients. METHODS: Patients who had undergone ≥2 GFR studies at our department between January 2009 and December 2019 were retrospectively identified. Patients with chronic kidney disease and those who had received chemotherapy, radiotherapy or surgery between measurements were excluded. The CV for each patient was calculated and the mean CVs of cancer and prospective renal donor groups were calculated and compared. RESULTS: Fifty-four patients were included in the final analysis. The mean CV in the cancer group (38 patients) was 8.5% [95% confidence interval (CI) 6.9-10.2%] and in the renal donor group (16 patients) 7.1% (95% CI 4.2-10.1%). These figures did not differ significantly (P = 0.37). The groups were combined to calculate the final overall mean CV of 8.1% (95% CI 6.7-9.6%). CONCLUSION: In both non-cancer and cancer patients the CV of GFR studies performed with 99mTc-DTPA was comparable with mostly 51Cr-EDTA figures presented in literature.

Estimated glomerular filtration rate in children: adapting existing equations for a specific population.

BACKGROUND: Creatinine-based glomerular filtration rate (GFR)-estimating equations frequently do not perform well in populations that differ from the development populations in terms of mean GFR, age, pathology, ethnicity, and diet. After first evaluating the performance of existing equations, the aim of this study was to demonstrate the utility of an in-house modification of the equations to better fit a specific population. METHODS: Estimated GFR using 8 creatinine-based equations was first compared to 2-sample 51Cr-ethylenediaminetetra-acetic acid plasma clearance in non-cancer and cancer groups independently. The groups were then divided into development and validation sets. Using the development set data, the Microsoft® Excel SOLVER add-in was used to modify the parameters of 7 equations to better fit the data. Using the validation set data, the performance of the original and modified equations was compared. RESULTS: Two hundred fifty-six GFR measurements were performed in 160 children. GFR was overestimated in both groups (non-cancer 4.3-22.6 ml/min/1.73 m2, cancer 17.2-46.6 ml/min/1.73 m2). The root mean square error (RMSE) was 19.1-21.8 ml/min/1.73 m2 (non-cancer) and 18.6-20.8 ml/min/1.73 m2 (cancer). The P30 values were 49.1-73.0% (non-cancer) and 19.6-66.0% (cancer). Modifying the parameters of seven equations resulted in significant improvements in the P30 values in the non-cancer (65.0-85.0%) and cancer (79.6-87.8%) groups. CONCLUSIONS: Modifying the parameters of pediatric GFR estimating-equations using a simple Excel-based tool significantly improved their accuracy in both non-cancer and cancer populations. Graphical abstract.

Validation of Glomerular Filtration Rate Measurement with Blood Sampling from the Injection Site.

Measurement of glomerular filtration rate (GFR) from the plasma clearance of a radionuclide-labeled tracer is reliable and accurate. However, to avoid contamination of the blood samples with radioactivity remaining at the injection site, venepuncture at 2 or more sites is required: one for tracer administration and the others for blood sampling. This requirement is uncomfortable for patients, particularly when venous access is difficult. The objective of this study was to validate the use of a single site of venous access in combination with injection site imaging, for GFR measurement. Methods: Twenty-two adults (≥18 y) who were referred for GFR determination were included prospectively. GFR was measured from the plasma clearance of 99mTc-diethylenetriaminepentaacetic acid according to international guidelines. After administration of the tracer through an intravenous cannula, a 60-s static image of the injection site was acquired. A second intravenous cannula was inserted into the contralateral arm. Venous blood samples were collected at 2, 3, and 4 h after administration of the radiotracer from both the injection site (experimental) and the contralateral arm (conventional). GFR was calculated using slope-intercept and single-sample methods. The median conventional and experimental plasma counts (decay- and background-corrected) were compared for the 2-, 3-, and 4-h venous samples. Conventional and experimental GFRs were then compared, with a more than 10% difference between conventional and experimental GFRs being regarded as significant. Results: Four individuals had visible residual activity at the injection site. The median 2-h counts differed significantly between the conventional and experimental sampling sites (P = 0.007), whereas no significant difference was found at 3 or 4 h. When there was a clear injection site image, the difference between the experimental and conventional GFRs was more than 10% in 1 case for single-sample GFR but less than 8% in all cases for slope-intercept GFR. Conclusion: In cases with clear injection site images, slope-intercept GFR calculated after injection site blood sampling showed no clinically significant difference from conventional contralateral-arm sampling.

Propagation of measurement errors in glomerular filtration rate determination: a comparison of slope-intercept, single-sample and slope-only methods.

BACKGROUND: Measurement errors occurring during glomerular filtration rate (GFR) studies propagate to an error in the calculated GFR. Previous work has modelled measurement errors for slope-intercept (SI-GFR), single-sample (SS-GFR) and slope-only (SO-GFR) methods. In this study, we have extended these models. The primary aims were to (i) compare measurement errors in two-sample SI-GFR, three-sample SI-GFR, SS-GFR and SO-GFR, and (ii) determine the sensitivity of GFR to errors arising from different measurements. PATIENTS AND METHODS: This study expanded on previous models of GFR measurement error incorporating biological data from 786 patients and realistic measurement errors. GFR median absolute error and the coefficient of variation (CV) were calculated for each method. A sensitivity analysis was carried out for individual measurement errors. RESULTS: The median absolute error ranged between 1.2 and 2.3 ml/min/1.73 m, lowest for SS-GFR (4 h) and highest for SO-GFR. At higher rates of clearance, CV was less than 5% for all methods. CV increased rapidly when GFR decreased below a threshold ranging between 34 and 56 ml/min/1.73 m, lowest for three-point SI-GFR and highest for SO-GFR. SI-GFR and SS-GFR are most sensitive to injected activity quantification, but less sensitive to other measurement errors. CONCLUSION: Measurement errors are probably insignificant relative to biological variation for GFR of more than 60 ml/min/1.73 m, but become significant irrespective of biological variation at lower GFR, particularly in serial studies when GFR less than 25 ml/min/1.73 m. Limits of precision recommended in the 2018 British Nuclear Medicine Society guideline are appropriate for once-off GFR measurement, whereas slightly more stringent limits are proposed for serial studies.

(99m)Tc-DTPA volume of distribution, half-life and glomerular filtration rate in normal adults.

BACKGROUND AND AIM: Assessment of volume of distribution (VD) and half-life (T1/2) values during glomerular filtration rate (GFR) investigations is a useful quality control check. The aim of this study was to derive reference data for VD and T1/2 and also to provide reference data for GFR from studies performed using Tc-diethylenetriaminepentaacetic acid (Tc-DTPA). METHODS: This was a retrospective study of 126 healthy potential kidney donors (age range 18-59 years). The GFR was evaluated from Tc-DTPA plasma clearance using the 2004 British Nuclear Medicine Society guidelines. The association between VD and body surface area (BSA) was assessed. T1/2 was correlated with age and GFR. The correlation between the Brochner-Mortensen-corrected GFR (BM-GFRCorr) and age was evaluated. RESULTS: The uncorrected VD value (l) was 10.1×BSA±40.6% (P<0.01). The corrected VD value (l) was 8.19×BSA±34.4% (P<0.01). In individuals under the age of 40 years, the mean T1/2 was 95.0 min±36.2%. In individuals aged 40 years and above, the T1/2 increased at a rate of 0.49 min/year (P=0.04); the T1/2 (min) was 9480×(1/BM-GFRCorr)±35.1% (P<0.01). In individuals younger than 40 years of age, the correlation between BM-GFRCorr and age was not statistically significant (P=0.45), and the mean GFR was 108 ml/min/1.73 m±27.5%. In individuals aged 40 years and above, the BM-GFRCorr was 170-(1.55×age) ml/min/1.73 m±36.7% (P<0.001). CONCLUSION: Well-defined reference data for VD and T1/2 can be used for quality control checks in GFR investigations. In addition to these, reference data for GFR using Tc-DTPA have been defined. This will enhance the interpretation of adult Tc-DTPA GFR measurements.