-Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[ 18 F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([ 11 C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin ϩ glucose euglycemic clamp conditions (120 mU·m Ϫ2 ·min Ϫ1 ) to 3-h saline infusion. Lean controls (n ϭ 10) were compared with glycemically controlled volunteers with T2DM (n ϭ 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P Ͻ 0.01) and significantly increased myocardial oxygen consumption (P ϭ 0.04) and perfusion (P ϭ 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P Ͻ 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P Ͻ 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P Ͻ 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P ϭ 0.003). Myocardial work efficiency was lower in T2DM (P ϭ 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P ϭ 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM. myocardial; heart; diabetes; metabolism; metabolic flexibility; positron emission tomography ALTERATIONS IN METABOLIC SUBSTRATE uptake and metabolism are part of the phenotype that defines type 2 diabetes mellitus (T2DM) (3,4,33,39,74). The phenomenon of "metabolic flexibility" is the capacity of an organism, a tissue bed, or a cell system to switch readily among fuel types. Impaired metabolic flexibility is another phenotypic feature of T2DM (33, 66).Impaired metabolic flexibility has been demonstrated in skeletal muscle in human diabetes (32,66). This whole body effect likely arises due to effects of impaired insulin-stimulated glucose uptake, together with abnormalities in availability, uptake, and metabolism of fatty acid fuels (33,66,75).The myocardium is also affected by T2DM. The fuel needs of the heart are dramatically different than those of skeletal muscle, supporting continuous work even under resting conditions. Abnormalities in myocardial fuel selection in animal models of diabetes have been described (42,54,75), including impairments in insulin-stimulated glucose uptake and impaired suppression of myocardial fatty acid u...

Purpose-This study was undertaken to evaluate radiation dosimetry for the prostate-specific membrane antigen targeted [ 68 Ga]Ga-P16-093 radiopharmaceutical, and to initially assess agent performance in positron emission tomography (PET) detection of the site of disease in prostate cancer patients presenting with biochemical recurrence.Procedures-Under IND 133,222 and an IRB-approved research protocol, we evaluated the biodistribution and pharmacokinetics of [ 68 Ga]Ga-P16-093 with serial PET imaging following intravenous administration to ten prostate cancer patients with biochemical recurrence. The recruited subjects were all patients in whom a recent [ 68 Ga]Ga-PSMA-11 PET/x-ray computed tomography (CT) exam had been independently performed under IND 131,806 to assist in decision-making with regard to their clinical care. Voided urine was collected from each subject at ~60 min and ~140 min post-[ 68 Ga]Ga-P16-093 injection and assayed for Ga-68 content. Following image segmentation to extract tissue time-activity curves and corresponding cumulated activity values, radiation dosimetry estimates were calculated using IDAC Dose 2.1. The prior Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. http://www.springer.com/gb/openaccess/authors-rights/aam-terms-v1

No abstract

These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection.

Conventional MRI has important limitations when assessing for progression of disease (POD) versus treatment-related changes (TRC) in patients with malignant brain tumors. We describe the observed impact and pitfalls of implementing 18 F-fluoroethyltyrosine ( 18 F-FET) perfusion PET/MRI into routine clinical practice. Methods: Through expanded-access investigational new drug use of 18 F-FET, hybrid 18 F-FET perfusion PET/MRI was performed during clinical management of 80 patients with World Health Organization central nervous system grade 3 or 4 gliomas or brain metastases of 6 tissue origins for which the prior brain MRI results were ambiguous. The diagnostic performance with 18 F-FET PET/MRI was dually evaluated within routine clinical service and for retrospective parametric evaluation. Various 18 F-FET perfusion PET/MRI parameters were assessed, and patients were monitored for at least 6 mo to confirm the diagnosis using pathology, imaging, and clinical progress. Results: Hybrid 18 F-FET perfusion PET/MRI had high overall accuracy (86%), sensitivity (86%), and specificity (87%) for difficult diagnostic cases for which conventional MRI accuracy was poor (66%). 18 F-FET tumor-to-brain ratio static metrics were highly reliable for distinguishing POD from TRC (area under the curve, 0.90). Dynamic tumor-to-brain intercept was more accurate (85%) than SUV slope (73%) or time to peak (73%). Concordant PET/MRI findings were 89% accurate. When PET and MRI conflicted, 18 F-FET PET was correct in 12 of 15 cases (80%), whereas MRI was correct in 3 of 15 cases (20%). Clinical management changed after 88% (36/41) of POD diagnoses, whereas management was maintained after 87% (34/39) of TRC diagnoses. Conclusion: Hybrid 18 F-FET PET/MRI positively impacted the routine clinical care of challenging malignant brain tumor cases at a U.S. institution. The results add to a growing body of literature that 18 F-FET PET complements MRI, even rescuing MRI when it fails.