[show abstract][hide abstract] ABSTRACT: Islet cell adaptation to insulin resistance in type 2 diabetes mellitus may be due in part to increased stimulation of beta cells by the autonomic nervous system. The parasympathetic neurotransmitter acetylcholine (ACh) mediates insulin release via M3 muscarinic receptors on islet beta cells. The vesicular ACh transporter (VAChT) receptor correlates with cholinergic activity in vivo. The positron emission tomography (PET) radiotracer (+)-4-[18F]fluorobenzyltrozamicol ([18F]FBT) binds to the VAChT receptor on presynaptic cholinergic neurons and can be quantified by PET. In this study, we utilize [18F]FBT PET to demonstrate pancreatic cholinergic activity before and after dextrose infusion in nonhuman primates with normal (NGT) and impaired (IGT) glucose tolerance.
Seven adult female vervet (Chlorocebus aethiops) monkeys were maintained on an atherogenic Western diet. They were divided into two groups: four with NGT and three with IGT. Each subject underwent [18F]FBT PET twice: first, a baseline PET under fasting conditions; and second, PET under fasting conditions but after intravenous infusion of dextrose solution. Quantitative analysis of pancreatic uptake at 60 min post-injection was performed.
There was no difference in pancreatic uptake of [18F]FBT on baseline scans between the two groups. Pancreatic uptake of [18F]FBT increased in every subject after dextrose infusion (P = 0.03). On post-dextrose PET scans, pancreatic uptake of [18F]FBT was significantly higher in IGT subjects compared with NGT subjects (P = 0.03). The post-dextrose to pre-dextrose uptake ratios were higher in IGT subjects (P = 0.08).
Acute increases in pancreatic cholinergic activity in vivo were detected in the pancreata of nonhuman primates with NGT and IGT after intravenous dextrose infusion on [18F]FBT PET. In subjects with IGT, this activity was significantly higher, suggesting increased autonomic nervous system stimulation of the pancreatic islets in insulin-resistant subjects.
[show abstract][hide abstract] ABSTRACT: Pancreatic neuronal changes associated with beta cell loss in type 1 diabetes mellitus are complex, involving, in part, parasympathetic mechanisms to compensate for preclinical hyperglycemia. The parasympathetic neurotransmitter acetylcholine (ACh) mediates insulin release via M3 muscarinic receptors on islet beta cells. The vesicular ACh transporter (VAChT) receptor has been shown to be a useful marker of cholinergic activity in vivo. The positron emission tomography (PET) radiotracer (+)-4-[(18)F]fluorobenzyltrozamicol ([(18)F]FBT) binds to the VAChT receptor on presynaptic cholinergic neurons and can be quantified by PET. The compound 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), available in a tritiated form, binds to M3 muscarinic receptors on beta cells and is a potential target for assessing pancreatic beta cell mass. In this study, we investigate the feasibility of dual radiotracer analysis in identifying neurofunctional changes that may signify type 1 diabetes mellitus in its early preclinical state.
Ex vivo determinations of pancreatic uptake were performed in prediabetic nonobese diabetic mice and controls after intravenous injection of [(18)F]FBT or 4-[(3)H]DAMP. Beta cell loss in prediabetic mice was confirmed using immunohistochemical methods.
[(18)F]FBT uptake was significantly higher in prediabetic pancreata than controls: 3.22 +/- 0.81 and 2.51 +/- 1.04, respectively (P < 0.03). 4-[(3)H]DAMP uptake was significantly lower in prediabetic pancreata than controls: 0.612 +/- 0.161 and 0.968 +/- 0.364, respectively (P = 0.01).
These data suggest that a combination of radiotracer imaging agents that bind to neuronal elements intimately involved in insulin production may be an effective method of evaluating changes associated with early beta cell loss using PET.
[show abstract][hide abstract] ABSTRACT: The incidence of parathyroid carcinoma is approximately 0.5% to 5% in patients with primary hyperparathyroidism. Recurrent parathyroid carcinoma is treated with surgical resection of all sites of disease to ameliorate systemic manifestations of hyperparathyroidism, primarily hypercalcemia. This study investigates the role of parathyroid scintigraphy and computed tomography (CT) imaging in recurrent parathyroid carcinoma.
A retrospective chart review was performed on 8 patients diagnosed with recurrent parathyroid carcinoma at our tertiary care institution between 1975 and 2001. Surgical reports, histopathology, parathyroid scintigraphy, and CT findings were recorded. Surgical reports and radiologic studies were compared for concordance of recurrence sites.
There were 32 imaging studies before reoperation: 15 parathyroid scintigraphy and 17 CTs. Of 15 sites of recurrence potentially seen on scintigraphy, 10 were true-positive (67%). Of 17 sites of recurrence potentially seen on CT, 9 were true-positive (53%). Of the 8 false-negatives on CT, 7 of these recurrences were in the surgical bed (88%). There were 9 instances in which CT and scintigraphy were performed preoperatively for comparison and correlation. CT and scintigraphic findings were incongruent in 7 of 9 of these cases (78%).
Successful surgical intervention for recurrent parathyroid carcinoma requires accurate preoperative localization studies and complete excision of metastases. Our data supports combined analysis of parathyroid scintigraphy and CT for patients with recurrent disease before reoperation. Additionally, our review suggests that sensitivity may be optimized with SPECT parathyroid scintigraphy and close correlation with CT.
Clinical Nuclear Medicine 12/2004; 29(11):681-4. · 2.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: Evaluation of high-risk mammograms represents an enormous clinical challenge. Functional breast imaging coupled with mammography (positron emission mammography [PEM]) could improve imaging of such lesions. A prospective study was performed using PEM in women scheduled for stereotactic breast biopsy.
Patients were recruited from the surgical clinic. Patients were injected with 10 mCi of 2-[18F] fluorodeoxyglucose. One hour later, patients were positioned on the stereotactic biopsy table, imaged with a PEM scanner, and a stereotactic biopsy was performed. Imaging was reviewed and compared with pathologic results.
There were 18 lesions in 16 patients. PEM images were analyzed by drawing a region of interest at the biopsy site and comparing the count density in the region of interest with the background. A lesion-to-background ratio >2.5 appeared to be a robust indicator of malignancy and yielded a sensitivity of 86%, specificity of 91%, and overall diagnostic accuracy of 89%. No adverse events were associated with the PEM imaging.
The data show that PEM is safe, feasible, and has an encouraging accuracy rate in this initial experience. Lesion-to-background ratios >2.5 were found to be a useful threshold value for identifying positive (malignant) results. This study supports the further development of PEM.
Annals of Surgical Oncology 01/2003; 10(1):86-91. · 4.12 Impact Factor