Scandium (Sc) is a promising candidate for theranostic applications due to the existence of radioisotopes suitable for both imaging and therapy. A “proof-of-concept” study regarding first-in-human use of 44Sc for imaging metastatic neuroendocrine tumors was reported recently, however, quantitative assessment of 44Sc-based PET images was not performed. The aim of this study was to evaluate quantitative capabilities of 44Sc-PET using a commercial PET scanner. The NEMA/IEC body phantom with 44Sc was acquired according to the local protocol used for whole-body oncological [18F]FDG PET examinations. Additionally, we characterized the signal recovery (recovery coefficient—RC) according to the iteration number. For all reconstructions, pertinent image corrections (normalization, dead time, activity decay, random coincidence, and attenuation) were applied. Presently, 44Sc scatter corrections are not optimized and could, thus, result in quantitative bias. To investigate the best option, the data were reconstructed using different available scatter corrections (relative -RelSC- and absolute -AbsSC-) and an additional prompt-gamma correction (PGC). System cross-calibration with the local dose calibrator (BGcal) and image noise, expressed by the coefficient of variation (COV), were evaluated in the homogeneous background region (5 kBq/mL) of the phantom. Maximum (RCmax) and 50% threshold recovery coefficients, corrected for background (RCA50), were measured for all spherical inserts (25 kBq/mL) of the phantom. Acceptable COV (<15%) was achievable with low iteration numbers (<3). BGcal differences were low: mean BGcal were 77.8, 81.3, and 86.7%, for RelSC, AbsSC, and PGC, respectively. RC values exceeded the present RC range recommended for [18F]FDG procedures. Using the iterations to be evaluated, RCA50 ranged from 29.9 to 59.9% for the smallest lesion (spherical insert of 10 mm diameter) and from 45.5 to 80.3% (13 mm), 66.4 to 75.6% (17 mm), 71.7 to 75.7% (22 mm), 75.1 to 78.6% (28 mm), and 76.7 to 80.9% (37 mm) for the, respectively spherical inserts. The results of this study show that clinical 44Sc-PET imaging has the potential to provide signal recovery in lesions of different sizes comparable to current 18F-PET standards. In order to improve the quantitative accuracy of 44Sc PET, optimized corrections are still necessary and will be investigated further in future.

ObjectiveTo determine parameters of perfusion, distribution coefficient, and glucose metabolism as part of the tumour-specific micromilieu of breast cancer and compare them with corresponding values in normal breast tissue. MethodsH215O PET and 18F-FDG PET were performed on 10 patients with advanced invasive ductal carcinomas of the breast. Perfusion, distribution coefficient, and glucose metabolism and standardized uptake were quantified and analysed. ResultsMean values based on the regions of interest were 59.2±43.9 ml · min−1 · 100 g−1 (perfusion), 0.58±0.26 ml · g−1(distribution coefficient), 7.76±6.10 (standardized uptake), and 5.4±2.5 mg · min−1 · 100 g−1 (glucose metabolism). The corresponding values for normal breast tissue were 22.1±13.2 ml · min−1 · 100 g−1 (perfusion), 0.16±0.05 ml · g−1 (distribution coefficient), 0.33±0.07 (standardized uptake), and 0.18±0.08 mg · min−1 · 100 g−1 (glucose metabolism). For each tumour–normal tissue parameter pair, the mean values were significantly higher in tumours than normal breast tissue. Region-of-interest and pixel-wise correlation analysis revealed a positive association between glucose metabolism and distribution coefficient and glucose metabolism and perfusion for 7/10 tumours investigated. ConclusionsH215O and 18F-FDG PET were able to differentiate breast cancer and normal breast tissue. The pixel-wise analysis revealed information about the heterogeneity of tumour fine structure in perfusion, distribution coefficient, and glucose metabolism, which may provide important guidelines for improving individual treatment.

RARE-MR-urography (Rapid Acquisition with Relaxation Enhancement) is a fast MR imaging technique (6.4 s/acquisition) that selectively depicts fluid by heavy T2-weighting. From 9/1989 to 11/1990, RARE-MR urograms were prospectively evaluated in the diagnosis of upper urinary tract abnormalities in 55 children. The method is performed in several planes and combined with a coronal, T1-weighted spin-echo sequence. Forty out of 42 kidneys with dilated renal pelvis, and 21 out of 24 dilated ureters were identified, only the mildly dilated ones were missed. Even in non-functioning kidneys the urinary tract was clearly depicted by RARE-MR-urography. However, no differentiation could be made with this technique between vesicoureteral reflux and non-refluxing dilatation of ureter and/or renal pelvis. All 19 pelviureteric obstructions and all eight renal duplications with a dilated segment were identified. RARE-MR-urography is a new tool for diagnosing urinary tract abnormalities in children without having to employ ionizing radiation, contrast media, or general anesthesia. A dilated urinary tract can be shown in one image displaying the entire urinary system, similar to excretory urography. The technique is presently not able to provide the information of voiding cystourethrography or renal scintigraphy, nor is it as easy to perform as ultrasound. However, in certain cases it may replace excretory urography.

Purpose: We evaluated the diagnostic accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) for detection of liver metastases in malignant melanoma.Material and methods: Thirtyfive patients with 39 combined unenhanced MRI and fluorine-18 deoxyglucose (F-18 FDG) PET scans were prospectively studied. In discordant imaging findings final diagnosis was proven by clinical follow-up > 6 months and demonstration of progressive liver metastases by at least one imaging method. Sensitivities and specificities were compared and the influence of lesion size and melanin content on diagnostic accuracy was determined.Results: MRI and PET were concordantly negative for presence and number of liver metastases in 28 patients and positive in four patients. PET and MRI were false positive in one patient each. In one patient MRI showed a single metastases not seen by PET and in one patient MRI demonstrated more metastases at the first examination. In follow-up investigations MRI revealed more metastases than PET in both patients. The sensitivities for lesion detection were 47% (16/34) for PET and 100% for MRI. Lesion detectability by PET was related to lesion size (P < 0.0001) but not to melanin content.Conclusion: MRI is more sensitive in the detection of liver metastases in patients with malignant melanoma. Small lesions are easily missed by PET, while melanin content does not influence detectability by PET. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Objective: To test the hypothesis that scintigraphic regional myocardial perfusion defects during exercise in patients with normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory in response to cold pressor testing.Methods: 38 patients were classified into two groups according to the presence or absence of exercise induced scintigraphic myocardial perfusion defects. A cold pressor test was done in all patients during routine coronary angiography, followed by dynamic positron emission tomography to establish coronary blood flow mediated vasoreactivity of the epicardial coronary artery and the myocardial territories supplied by the left anterior descending, left circumflex, and right coronary arteries.Results: 28 patients had regional myocardial perfusion defects while 10 had normal scintigraphic imaging. The three dimensional scintigraphic fusion image revealed 49 regional myocardial perfusion defects with a mean (SD) reversibility of the original stress defect of 20 (3)%. In patients with exercise induced regional myocardial perfusion defects, the responses of epicardial luminal area and regional myocardial blood flow (RMBF) to cold pressor testing were reduced compared with patients with normal perfusion imaging (epicardial luminal area: 5.2 (1.2) to 4.2 (0.86) mm(2) v 4.7 (0.5) to 5.8 (0.5) mm(2); RMBF: 0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.15) to 1.38 (0.26) ml/g/min; p < 0.03, respectively). In patients with regional abnormal scintigraphic perfusion, the corresponding RMBF response to cold pressor testing was more severely impaired than the mean myocardial blood flow in the remaining two vascular territories, but the difference was not significant (0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.10) to 0.87 (0.12) ml/g/min; NS). The endothelium independent increase in RMBF induced by glyceryl trinitrate did not differ between patients with exercise induced myocardial perfusion defects and those with normal perfusion images (0.75 (0.16) to 0.94 (0.09) ml/g/min v 0.75 (0.15) to 0.94 (0.09) ml/g/min; NS). There was a highly significant correlation between the endothelium dependent responses of RMBF to cold pressor testing and the severity of exercise induced scintigraphic regional myocardial perfusion defects (r = 0.95, p = 0.001).Conclusions: Exercise induced scintigraphic regional myocardial perfusion defects in patients with angina but normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory.

PURPOSE:To evaluate fluorine 18 ((18)F) dihydroxyphenylalanine (DOPA) whole-body positron emission tomography (PET) as a biochemical imaging approach for detection of pheochromocytomas.MATERIALS AND METHODS:(18)F DOPA PET and magnetic resonance (MR) imaging were performed in 14 consecutive patients suspected of having pheochromocytomas (five sporadic, nine with von Hippel-Lindau disease); metaiodobenzylguanidine (MIBG) scintigraphy was performed in 12 of these patients. The individual imaging findings were assessed in consensus by specialists in nuclear medicine and radiologists blinded to the results of the other methods. The findings of the functional imaging methods were compared with those of MR imaging, the reference standard. Histologic verification could be obtained in eight patients with nine tumors.RESULTS:Seventeen pheochromocytomas (11 solitary, three bifocal; 14 adrenal, three extraadrenal) were detected with MR imaging. (18)F DOPA PET and MR imaging had concordant results in all 17 tumors. In contrast, MIBG scintigraphy had false-negative results in four patients with three adrenal tumors smaller than 2 cm and one extraadrenal tumor with a diameter of 3.6 cm. On the basis of these data, sensitivities of 100% for (18)F DOPA PET and of 71% for MIBG scintigraphy were calculated. Specificity was 100% for both procedures.CONCLUSION:(18)F DOPA PET is highly sensitive and specific for detection of pheochromocytomas and has potential as the functional imaging method of the future.

Objective The impact of the (2-(fluorine-18)-fluoro-2-2deoxy-D-glucose)-positron emission tomography (F-18-FDO-PET) for discrimination of pulmonary lesions was evaluated in a single centre prospective study. Methods: In the study, 109 patients with pulmonary lesions of unknown origin verified by computed tomography were enrolled consecutively (April 1999-May 2000). They were subject to F-18-FDG-PET diagnostics. 18F-FDG-PET images were interpreted by two independent nuclear medicine physicians who were blinded to the results of other imaging procedures. In 87 patients, surgery was applied followed by histological investigation, which served as the gold standard. In 22 other patients, extensive tumour load or assumed benign dignity of the lesions prevented surgery. Results: Overall sensitivity of F-18-FDG-PET in 87 resected patients was 0.86. Differentiation in malignant (n = 69) and benign lesions (n = 18) revealed sensitivities of 0.9 and 0.72, respectively. Sensitivity of F-18-FDG-PET in inflammatory lesions was markedly lower (0.43) than in benign tumours (0.91). Standard uptake values were significantly increased in malignant tumours compared with benign lesions (9.9 and 1.6, respectively; P = 0.035). There was a clear correlation of sensitivity with tumour size with a failure rate of 27% in lesions less than or equal to1 cm (n = 15), 10% (n = 20) in lesions between 1 and 2 cm and 12% (n = 45) above 2 cm. In primary bronchial carcinoma, a clear correlation of sensitivity was observed with regard to tumour grading (G1, three out of five; G2, 24 out of 27; G3, 26 out of 26; and G4, one out of one). Lymph node involvement was correctly suggested in 10 out of 19 (52.6%) patients. However, false positive lymph node enhancement was indicated in one out of IS (5.5%) operated patients with benign lesions and eight out of 39 (20.5%) with bronchial carcinoma. Conclusion: 18F-FDG-PET at present does not serve as the gold standard for early detection of small and well-differentiated tumours. However, it contributes efficiently to the detection of malignancy in tumours >1 cm, which are moderately or poorly differentiated. Positive lymph node imaging must not preclude surgery but requires histological proof. Discrimination of benign and malignant pulmonary tumours by F-18-FDG-PET appears to be hampered in inflammatory lesions. (C) 2001 Elsevier Science B.V. All rights reserved.

PURPOSE:To evaluate fluorine 18 (18F) dopa positron emission tomography (PET) in comparison with established imaging procedures in gastrointestinal carcinoid tumors.MATERIALS AND METHODS:After evaluation of the normal distribution of 18F dopa, 17 patients with histologically confirmed tumors were examined with 18F dopa PET. Results of 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) PET, somatostatin-receptor scintigraphy, and morphologic imaging (computed tomography and/or magnetic resonance imaging) were available for all patients. Results of the procedures were evaluated by two radiologists and two nuclear medicine specialists, whose consensus based on all available histologic, imaging, and follow-up findings was used as the reference standard.RESULTS:Ninety-two tumors were diagnosed: eight primary tumors, 47 lymph node metastases, and 37 organ metastases. 18F dopa PET led to 60 true-positive findings (seven primary tumors, 41 lymph node metastases, 12 organ metastases); FDG PET, 27 (two primary tumors, 14 lymph node metastases, 11 organ metastases); somatostatin-receptor scintigraphy, 52 (four primary tumors, 27 lymph node metastases, 21 organ metastases); and morphologic imaging, 67 (two primary tumors, 29 lymph node metastases, 36 organ metastases). This resulted in the following overall sensitivities: 18F dopa PET, 65% (60 of 92); FDG PET, 29% (27 of 92); somatostatin-receptor scintigraphy, 57% (52 of 92); morphologic procedures, 73% (67 of 92). Although the morphologic procedures were most sensitive for organ metastases, 18F dopa PET enabled best localization of primary tumors and lymph node staging.CONCLUSION:18F dopa PET is a promising procedure and useful supplement to morphologic methods in diagnostic imaging of gastrointestinal carcinoid tumors.

Little information is available on intervention studies to prove the relation of dietary intake of antioxidants and prevention of coronary heart disease. We tested the hypothesis that regular intake of 2g of ascorbic acid (aa) daily could improve endothelial dysfunction (ED) of coronary microcirculation in hypertensive pts.(HT), chronic smokers (CS), and in hypercholesterolemic pts.(HC) compared to placebo administration (PA) and control (CO) over a 2 years follow-up. Methods and Results: 40pts. with evidence for ED of epicardial coronary artery based upon cold pressor testing (CPT) and 10 pts. with normal findings (CO) were entered and grouped as follows: 12 HT+ED, 10 CS+ED, 10 HC+ED, 8 HT+ED but PA and 10 pts. without ED but aa for CO. All patients underwent dynamic positron-emission-tomography (PET) measurements at baseline and during CPT before and immediately after i.v. infusion of 3g aa and, repeated again, after 3 months as well as after a 2 years follow-up of regular intake of 2g aa daily. Myocardial blood flow (MBF) was quantified by dynamic PET measurements. The effect of CPT is expressed as mean percent change (mean+/-SEM) in MBF (%DMBF) relative to baseline (Table1; pless than or equal to0.03 vs. CPT). Results:The CPT induced increase of mean %DMBF in hypertensive pts. and in chronic smokers after a 3 months and 2 years follow-up of regular oral intake of aa was significant compared to placebo and controls (p<0.03). Conclusion: Regular ascorbic acid supplementation effectively reverses impaired endothelium-dependent vasodilation of coronary microcirculation in hypertensive patients and in chronic smokers with sustained effect over 2 years.

In chronic smokers there is evidence that increased formation of oxygen derived free radicals within the vessel wall impair endothelial function. It has been suggested that the inactivation of endothelium-derived nitric oxide (NO) by oxygen free radicals contributes to endothelial dysfunction. Hence, we tested the hypothesis that in chronic smokers the antioxidant vitamin C (VC) could improve abnormal endothelial function of epicardial coronary arteries.Method: Thirty-one patients without angiographically significant CAD underwent cold pressor testing (CPT) to assess endothelium-dependent vasomotor response of epicardial artery before and after i.v. infusion of 3g of VC or 100ml 0.9% NaCl infusion.Results: In 6 controls without coronary risk factors CPT led to a similar increase of luminal area before and after VC administration (26.5 +/- 1.5.0% vs. 28.4 +/- 17.7% P = NS). In 15 chronic smokers CPT induced a decrease of luminal area of -18.5 +/- 6.3%. This flow-dependent vasoconstriction was significantly reversed to 7.7 +/- 6.2% (p less than or equal to 0.03) vasodilation after i.v. VC administration. In 10 chronic smokers saline infusion (placebo) did not have a significant effect on CPT-induced vasoconstriction (-12.7 +/- 5.1% vs. -13.1 +/- 5.1%, P = NS). The CPT- induced increase in luminal area in chronic smokers after VC infusion was significant as compared to controls and placebo (each p less than or equal to 0.05) (Figure). Furthermore, the assessment of endothelium-independent vasodilation induced by nitroglycerin revealed no significant differences between the study groups, indicating that vitamin C did not influence the responsivness of smooth muscle cells to exogenous application of nitric oxide (Figure).Conclusion: In chronic smokers acute i.v. administration of VC improves significantly endothelial dysfunction of epicardial coronary artery.

Little information is available on intervention studies to prove the relation of dietary intake of antioxidants and prevention of coronary heart disease. We tested the hypothesis that regular intake of 2g of ascorbic acid (aa) daily could improve endothelial dysfunction (ED) of coronary microcirculation in hypertensive pts.(HT), chronic smokers (CS), and in hypercholesterolemic pts.(HC) compared to placebo administration (PA) and control (CO) over a 2 years follow-up.Methods and Results: 40pts. with evidence for ED of epicardial coronary artery based upon cold pressor testing (CPT) and 10 pts. with normal findings (CO) were entered and grouped as follows: 12 HT+ED, 10 CS+ED, 10 HC+ED, 8 HT+ED but PA and 10 pts. without ED but aa for CO. All patients underwent dynamic positron-emission-tomography (PET) measurements at baseline and during CPT before and immediately after i.v. infusion of 3g aa and, repeated again, after 3 months as well as after a 2 years follow-up of regular intake of 2g aa daily. Myocardial blood flow (MBF) was quantified by dynamic PET measurements. The effect of CPT is expressed as mean percent change (mean +/- SEM) in MBF (%DMBF) relative to baseline (Table1; p less than or equal to 0.03 vs. CPT).Results: The CPT induced increase of mean %DMBF in hypertensive pts. and in chronic smokers after a 3 months and 2 years follow-up of regular oral intake of aa was significant compared to placebo and controls (p less than or equal to 0.03).Conclusion: Regular ascorbic acid supplementation effectively reverses impaired endothelium-dependent vasodilation of coronary microcirculation in hypertensive patients and in chronic smokers with sustained effect over 2 years.

BACKGROUND:Does transmyocardial laser revascularization (TMLR), a new surgical technique for treating patients with otherwise intractable angina pectoris, improve myocardial perfusion, metabolism, and, consequently, function?METHODS:Patients referred for TMLR, alone or with coronary artery bypass grafting (CABG), were preoperatively evaluated clinically and by treadmill stress testing, echocardiography, ventriculography, radionuclide assessment of perfusion and metabolism, and hemodynamic assessment. Intraoperatively it was decided that some patients only required CABG. Follow-up evaluations were repeated after 6 (n = 40) and 12 months (n = 23) and compared with preoperative values.RESULTS:CABG only was performed in 35 cases, TMLR + CABG in 17, TMLR only in 45. 1-year mortality was 11% in the TMLR, zero in the TMLR + CABG, and 11% in the CABG groups. In all groups a significantly improved CCS angina- and NYHA class was observed immediately after operation and after 6 and 12 months. In all study groups treadmill tolerance (p<0.05) improved, but regional and global function, perfusion at rest, and metabolism were not significantly changed at 6 and 12-months follow-ups. Perfusion studies under stress demonstrated an improvement only in the CABG group after 12 months (p<0.05), whereas in both TMLR groups the lasered ischemic segments remained unchanged.CONCLUSIONS:TMLR significantly improves long-term clinical status and treadmill stress tolerance, but appears to have little if any effect upon regional and global function, perfusion, and metabolism.

In patients with coronary artery disease coronary angiography plays an important role in the clinical decision-making process. However, it has been recognized that no simple relation exists between the visually or quantitatively evaluated severity of coronary artery stenoses and its effects on regional myocardial perfusion. This paper describes for the first time the development and application of a 3D technique that visualizes and quantifies regional myocardial perfusion parameters from biplane coronary angiograms by using the impulse response analysis technique. The 3D reconstructed coronary tree is automatically superimposed on the 3D perfusion image to generate and visualize an 'integrated' 3D image. The preliminary results in patients with critical coronary artery stenoses indicate that our combined 3D fusion image provides flow information from the major coronary arteries. This 3D fusion image may provide useful information in the management of patients with coronary artery disease.