Cost-effectiveness Analysis of 99mTc-sestamibi SPECT/CT to Guide Management of Small Renal Masses.

BACKGROUND: Incidentally detected small renal masses (SRMs) may be one of several benign or malignant tumor histologies, and are heterogeneous in oncologic potential. Renal mass biopsy can be used to determine the histology of SRMs. However, this invasive approach has significant limitations. Technetium-99m sestamibi single photon emission computed tomography/computed tomography (99mTc-sestamibi SPECT/CT) is a promising imaging tool that can aid in identifying benign renal oncocytomas and hybrid oncocytic/chromophobe tumors. OBJECTIVE: To evaluate the clinical and economic value of 99mTc-sestamibi SPECT/CT in guiding the management of SRMs. DESIGN, SETTING, AND PARTICIPANTS: We developed a decision analysis model to estimate the costs and health outcomes of competing management strategies for a healthy 65-yr-old patient with an asymptomatic SRM. INTERVENTION: Empiric surgery (reference); real-world clinical practice (RWCP) consisting of empiric surgery, thermal ablation, and active surveillance (alternative reference); renal mass biopsy (option 1); 99mTc-sestamibi SPECT/CT (option 2); and 99mTc-sestamibi SPECT/CT followed by biopsy to confirm benign SRMs (option 3). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed lifetime health utilities, measured in quality-adjusted life years (QALYs), and direct medical costs from a health payer perspective. We calculated the incremental cost-effectiveness ratio (ICER) for options 1-3 versus the reference and alternative reference arms, with a willingness-to-pay threshold of $50 000/QALY. Univariate, multivariate, and probabilistic sensitivity analyses were performed. RESULTS AND LIMITATIONS: Option 3 had a very low risk of untreated malignant tumors (0.2%, vs 2.1% for option 1, 4.2% for option 2, and 0% for empiric surgery) and the highest probability of leaving benign tumors untreated (84.4%, vs 53.9% for option 1, 51.7% for option 2, and 0% for empiric surgery). Option 3 dominated empiric surgery and options 1 and 2 (ie, lower costs and higher QALYs). Compared with RWCP, options 1-3 were all cost effective; option 3 had the lowest ICER of $18 821/QALY. These findings were robust to alternative input values. Study limitations included data uncertainties and a limited number of centers from which 99mTc-sestamibi SPECT/CT performance data were collected. CONCLUSIONS: 99mTc-sestamibi SPECT/CT followed by confirmatory biopsy helps avoid surgery for benign SRMs, minimizes untreated malignant SRMs, and is cost effective compared with existing strategies. PATIENT SUMMARY: Our research suggests that by using a noninvasive imaging test, known as technetium-99m sestamibi single photon emission computed tomography/computed tomography, to diagnose small renal masses, urologists may avoid unnecessary surgery for benign tumors and minimize the risk of leaving a malignant tumor untreated. Moreover, the use of this strategy to diagnose small renal masses is cost effective for the health care system.

Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay.

BACKGROUND: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. MATERIAL AND METHODS: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with 18F­2­fluoro­2­deoxy­d­glucose (18F-FDG) and 125I­ß­methyl­iodophenyl­pentadecanoic acid (125I-BMIPP) as transport markers of glucose and fatty acids, respectively. RESULTS: After cardiac differentiation of hiPSCs, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. CONCLUSIONS: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.

Transient ischemic dilation ratio in 82Rb PET myocardial perfusion imaging: normal values and significance as a diagnostic and prognostic marker.

UNLABELLED: In myocardial perfusion SPECT, transient ischemic dilation ratio (TID) is a well-established marker of severe ischemia and adverse outcome. However, its role in the setting of (82)Rb PET is less well defined. METHODS: We analyzed 265 subjects who underwent clinical rest-dipyridamole (82)Rb PET/CT. Sixty-two subjects without a prior history of cardiac disease and with a normal myocardial perfusion study had either a low or a very low pretest likelihood of coronary artery disease or negative CT angiography. These subjects were used to establish a reference range of TID. In the remaining 203 patients with an intermediate or high pretest likelihood, subgroups with normal and abnormal TID were established and compared with respect to clinical variables, perfusion defect scores, left ventricular function, and absolute myocardial flow reserve. Follow-up was obtained for 969 ± 328 d to determine mortality by review of the social security death index. RESULTS: In the reference group, TID ratio was 0.98 ± 0.06. Accordingly, a threshold for abnormal TID was set at greater than 1.13 (0.98 + 2.5 SDs). In the study group, 19 of 203 patients (9%) had an elevated TID ratio. Significant differences between subgroups with normal and abnormal TID ratio were observed for ejection fraction reserve (5.0 ± 6.4 vs. 1.8 ± 7.9; P < 0.05), difference between end-systolic volume (ESV) at rest and stress (ΔESV[stress-rest]; 1.8 ± 7.4 vs. 12.3 ± 13.0 mL; P < 0.0001), difference between end-diastolic volume (EDV) at rest and stress (ΔEDV[stress-rest]; 10.8 ± 11.5 vs. 23.8 ± 14.6 mL; P < 0.0001), summed rest score (1.8 ± 3.8 vs. 3.8 ± 7.6; P < 0.05), summed stress score (3.0 ± 5.4 vs. 7.5 ± 9.8; P < 0.002), summed difference score (1.3 ± 2.6 vs. 3.7 ± 5.3; P < 0.02), and global myocardial flow reserve (2.1 ± 0.8 vs. 1.7 ± 0.6; P < 0.02). Additionally, TID-positive patients had a significantly lower overall survival probability (P < 0.05). In a subgroup analysis of patients without regional perfusion abnormalities, TID-positive patients' overall survival probability was significantly smaller (P < 0.03), and TID was an independent predictor (exponentiation of the B coefficients [Exp(b)] = 6.22; P < 0.009) together with an ejection fraction below 45% (Exp[b] = 6.16; P < 0.002). CONCLUSION: The present study suggests a reference range of TID for (82)Rb PET myocardial perfusion imaging that is in the range of previously established values for SPECT. Abnormal TID in (82)Rb PET is associated with more extensive left ventricular dysfunction, ischemic compromise, and reduced global flow reserve. Preliminary outcome analysis suggests that TID-positive subjects have a lower overall survival probability.