Episodic memory impairment in frontotemporal dementia; a 99mTc- HMPAO SPECT study.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common types of dementia in the presenile population. Episodic memory impairment, the clinical hallmark of AD, can also be encountered in patients with FTD, complicating accurate diagnosis. Several studies in FTD have correlated memory deficits with neuroimaging findings, but lacked to compare neuroimaging results in FTD patients with and without memory impairment, while this latter analysis may give us insight into the underlying mechanisms of memory impairment in FTD. The aim of the present study was to compare (99m)Tc-HMPAO SPECT hypoperfusion patterns between FTD with episodic memory impairment (n = 13), FTD patients without episodic memory impairment (n = 10) as well as early onset (< 70 yrs) AD patients (n = 13), and controls (n = 15). We performed our analyses by means of Statistical Parametric Mapping software (SPM5), and showed that FTD patients with episodic memory impairment had lower perfusion in the right temporal lobe compared with FTD patients without memory impairment. Lower perfusion in this region correlated with worse memory performance on the Clinical Dementia Rating scale in FTD patients. With equal performances on memory tests, patients with early onset AD showed posterior temporal and parietal lobe hypoperfusion in comparison with patients with FTD and memory impairment, while vice versa hypoperfusion in the anterior frontotemporal regions was found in FTD patients with memory impairment in comparison with AD.

Midcingulate involvement in progressive supranuclear palsy and tau positive frontotemporal dementia.

BACKGROUND: Progressive supranuclear palsy (PSP) patients often exhibit cognitive decline and behavioural changes during the disease course. In a subset, these symptoms may be the presenting manifestation and can be similar to those in frontotemporal dementia (FTD). However, correlation studies between quantitative imaging measures and detailed neuropsychological assessment are scarce. The aim of this study was to investigate the functional role of affected brain regions in cognition in PSP compared with controls and subsequently examine these regions in FTD patients with known tau pathology (FTD tau). METHODS: 21 PSP patients, 27 healthy controls and 11 FTD tau patients were enrolled. All participants underwent neuropsychological testing and technetium-99m-hexamethyl-propylenamine-oxime single photon emission CT. Regression slope analyses were performed in statistical parametric mapping to find significant associations between neuropsychological test results and brain perfusion. RESULTS: PSP patients showed hypoperfusion in the midcingulate cortex (MCC) of which the posterior part correlated with Stroop III and Weigl. In FTD tau patients, MCC involvement was located more anterior and correlated with Stroop III and Wisconsin Card Sorting Test concepts. The degree of hypoperfusion in the anterior cortex and MCC in the disorders differed in the subgenual anterior cingulate cortex only. CONCLUSIONS: The posterior part of the MCC is prominently involved in the neurodegenerative process of PSP, and the severity of its hypoperfusion correlated with the extent of executive dysfunction. In FTD tau, this cognitive domain was associated with anterior MCC involvement. The degree of hypoperfusion in these regions did not differ between PSP and FTD tau. These observations provide insight into the role of the cingulate cortex in cognitive dysfunction in these neurodegenerative disorders and warrant further investigations.

Diagnostic imaging of dopamine receptors in pituitary adenomas.

Dopamine D2 receptor scintigraphy of pituitary adenomas is feasible by single-photon emission computed tomography using (123)I-S-(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-iodo-6-methoxybenzamide ((123)I-IBZM) and (123)I-epidepride. (123)I-epidepride is generally superior to (123)I-IBZM for the visualization of D2 receptors on pituitary macroadenomas. However, (123)I-IBZM and (123)I-epidepride scintigraphy are generally not useful to predict the response to dopaminergic treatment in pituitary tumour patients. These techniques might allow discrimination of non-functioning pituitary macroadenomas from other non-tumour pathologies in the sellar region. Dopamine D2 receptors on pituitary tumours can also be studied using positron emission tomography with (11)C-N-raclopride and (11)C-N-methylspiperone.

Dopamine agonist therapy of clinically non-functioning pituitary macroadenomas. Is there a role for 123I-epidepride dopamine D2 receptor imaging?

OBJECTIVE: Clinically non-functioning pituitary adenomas (NFPAs) can express functional dopamine D2 receptors. Therapy with dopamine (DA) agonists may result in a NFPA size reduction. However, DA agonist-sensitive and -resistant NFPAs are clinically indistinguishable. We have studied the correlation between in vivo imaging of D2 receptors using (123)I-epidepride and the radiological response of NFPA to DA in 18 patients. METHODS: Patients were treated with either cabergoline (1-2 mg/week) or quinagolide (150-300 mug/day) for a mean period of 89.7 months (range, 34-187 months). RESULTS: Pituitary uptake of (123)I-epidepride varied from slight uptake classified as grade 0 to very high classified as grade 3. Grade 0 uptake was found in four patients; grade 1 in three; grade 2 in ten, and grade 3 in one. NFPA stabilization or shrinkage with DA agonist therapy showed no significant difference between grade 0, 1, and 2 tumors (mean tumor stabilization or shrinkage: 31, 30, and 36% respectively). However, when we considered a decrease in tumor size ranging from 0 to 20% as tumor stabilization and >20% decrease in tumor size as true shrinkage, one out of four NFPAs with grade 1 uptake, two out of three with grade 1 uptake, and eight out of ten with grade 2 uptake showed tumor shrinkage. CONCLUSION: In conclusion, there is limited clinical usefulness of dopamine D2 receptor imaging for predicting the clinical efficacy of DA agonist in selected patients with NFPAs. DA agonist therapy in NFPAs can result in tumor stabilization and shrinkage.

Site-specific intracoronary delivery of octreotide in humans: a pharmacokinetic study to determine dose-efficacy in restenosis prevention.

Somatostatin analogues have been shown to inhibit smooth muscle cell proliferation after local administration in vivo in animal models and in vitro using human coronary smooth muscle cell cultures. However, the optimal dosage for attaining effective site-specific administration remains undefined. This study was performed to determine the required theoretical dose of the somatostatin analogue, octreotide, to be delivered site specifically, for prevention of restenosis after coronary angioplasty in humans using a previously described methodology to determine regional pharmacokinetics of site-specific intracoronary administrated compounds. In 7 patients, 111In-octreotide, a gamma-labeled somatostatin analogue, was infused post angioplasty at the site of dilatation via a coil-balloon and quantified using a radio-isotopic technique. Efficiency of delivery ranged from 0.1% to 2.7% of the total infused dose of 0.18 microg, corresponding to a mean peak delivered amount of 1.8 +/- 1.9 ng. Total locally bioavailable 111In-octreotide reached 2.28 +/- 2.15 ng h. Based on current in vitro bioavailability and peak concentration data to inhibit proliferation and thymidine incorporation in human coronary smooth muscle cells, a 4000x higher averaged dose (approximately 700 microg) should be infused site specifically to obtain a biologic efficacy in 50% of the treated patients (ED50). Quantification of regional pharmacokinetics enables the determination of a theoretical site-specific dose for achieving appropriate bioavailability above the therapeutic threshold concentration for smooth muscle cell inhibition. This approach is proposed for the determination of the appropriate site-specific coronary infusion dose for the inhibition of restenosis after balloon angioplasty.

Feasibility and image quality of dual-isotope SPECT using 18F-FDG and (99m)Tc-tetrofosmin after acipimox administration.

UNLABELLED: Currently, with the rapidly increasing number of patients with heart failure due to chronic coronary artery disease, the need for viability studies to guide treatment in these patients is increasing. The most accurate method for viability assessment is metabolic imaging with (18)F-FDG with PET or SPECT. To obtain excellent image quality in all patients, the (18)F-FDG studies should be performed during hyperinsulinemic euglycemic clamping. However, this approach is time-consuming and is not feasible in busy nuclear medicine laboratories. Recently, the use of a nicotinic acid derivative, acipimox, has been suggested, but limited data are available on the image quality of the (18)F-FDG studies using this approach. METHODS: We evaluated the feasibility and image quality of (18)F-FDG SPECT (with dual-isotope simultaneous acquisition (DISA) using (99m)Tc-tetrofosmin to assess perfusion) after acipimox administration in 50 nondiabetic patients. The image quality of both (18)F-FDG and (99m)Tc-tetrofosmin was assessed visually and quantitatively using myocardium-to-blood-pool (M/B) ratios as a measure of target-to-background ratio. The image quality and diagnostic value of DISA (99m)Tc-tetrofosmin SPECT was compared with standard (99m)Tc-tetrofosmin SPECT at baseline. RESULTS: After acipimox administration, the plasma levels of free fatty acids were extremely low (68 +/- 89 nmol/L). No severe side effects were observed, only paroxysmal flushing. The (18)F-FDG image quality was good in 46 patients (92%) and moderate but still interpretable in the other 4 patients (8%). The clinical information of the baseline (99m)Tc-tetrofosmin SPECT was retained in the DISA (99m)Tc-tetrofosmin SPECT images because we did observe no substantial fill-in of perfusion defects by high (18)F-FDG uptake in the same segment. CONCLUSION: Cardiac (18)F-FDG SPECT after acipimox is safe and resulted consistently in good image quality; this simple approach may be the method of choice for routine cardiac metabolic imaging.