PETC/CT with 18F-Choline localizes hyperfunctioning parathyroid adenomas equally well in normocalcemic hyperparathyroidism as in overt hyperparathyroidism.

PURPOSE: Identification of pathologic parathyroid glands in primary hyperparathyroidism, traditionally based on neck ultrasound (US) and/or 99mTc-Sestamibi scintigraphy, can be challenging. PET/CT with 18F-Fluorocholine (18F-FCH) might improve the detection of pathologic parathyroid glands. We aimed at comparing the diagnostic performance of 18F-FCH-PET/CT with that of dual-phase dual-isotope parathyroid scintigraphy and neck US. METHODS: Thirty-four consecutive patients with primary hyperparathyroidism were prospectively enrolled, 7 had normocalcemic hyperparathyroidism, and 27 had classic hypercalcemic hyperparathyroidism. All patients underwent high-resolution neck US, dual-phase dual-isotope 99mTc-Pertechnetate/99mTc-Sestamibi scintigraphy, and 18F-FCH-PET/CT. RESULTS: In the whole patients' group, the detection rates of the abnormal parathyroid gland were 68% for neck US, 71% for 18F-FCH-PET/CT, and only 15% for 99mTc-Sestamibi scintigraphy. The corresponding figures in normocalcemic and hypercalcemic hyperparathyroidism were 57 and 70% for neck US, 70 and 71% for 18F-FCH-PET/CT, and 0 and 18% for 99mTc-Sestamibi scintigraphy, respectively. In the 17 patients in whom the abnormal parathyroid gland was identified, either at surgery or at fine needle aspiration cytology/biochemistry, the correct detection rate was 82% for neck US, 89% for 18F-FCH-PET/CT, and only 17% for 99mTc-Sestamibi scintigraphy. CONCLUSIONS: 18F-FCH-PET/CT can be considered a first-line imaging technique for the identification of pathologic parathyroid glands in patients with normocalcemic and hypercalcemic hyperparathyroidism, even when the parathyroid volume is small.

Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis.

AIM: During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. MATERIALS AND METHODS: We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). RESULTS: Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). CONCLUSION: Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Systemic vascular inflammation in abdominal aortic aneurysm patients: a contrast-enhanced PET/CT study.

AIM: The aim of this paper was to investigate the presence of systemic vascular inflammation and its relationship with risk factors and biomarkers of systemic inflammation related to atherosclerosis in asymptomatic abdominal aortic aneurysm (AAA) patients. METHODS: Thirty AAA patients and 30 age-matched controls underwent contrast-enhanced 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET/CT. C-reactive protein, erythrocyte sedimentation rate, white blood cell count and differential, serum fibrinogen, D-dimer and full lipid panel were also evaluated. Region of interest analyses were performed to obtain target-to-background (TBR) metabolism of aorta, subclavian, carotid, iliac arteries and AAA. CT-based arterial calcium load (CL) was evaluated. Arterial Metabolism and CL intergroup differences were tested (unpaired t-test). Linear regression analysis was performed only between blood biomarkers on one side and both TBR and ACL of the arterial districts that resulted significantly different between patients and controls on the other. In all the analyses P values <0.05 were considered significant. RESULT: FDG-uptake was higher with respect to controls in aorta, carotid and iliac arteries (P<0.01, P<0.007, P<0.04 respectively). AAA and aorta metabolism showed an inverse correlation with HDL-chol (P<0.02 and P<0.01, respectively) while only aorta showed a direct correlation with lymphocytes' count (P<0.02). Carotid metabolism was directly correlated with monocytes' count and C-reactive protein concentration (P<0.02 and P<0.004, respectively). CONCLUSION: The present findings support the relevance of systemic vascular inflammation in all phases of atherosclerosis-related disorders. Moreover they confirm the concept that acute ischemic syndromes might represent the local result of a systemic inflammation rather than the focal involvement of a single arterial lesion.

A study of the efficacy of radioiodine therapy with individualized dosimetry in Graves' disease: need to retarget the radiation committed dose to the thyroid.

Although Iodine-131 (131I) therapy is fully validated for Graves' disease (GD), there is debate about radioiodine amount to be administered (prescribed activity), as well as the use of individualized dosimetry vs fixed 131I activity. The clinical outcome of 119 GD patients treated with 131I from 2003 to 2008 has been evaluated. The prescribed activity was calculated according to a dosimetric protocol taking into account several variables, including thyroid volume reduction during treatment. In addition, we performed a simulation according to other dosimetric protocols, by calculating the corresponding prescribed activities. The patients were followed up for at least 12 months after treatment. In the first period of observation (2003), a 120-200 Gray (Gy) radiation dose to the thyroid was prescribed, according to the guidelines published by the Italian Societies of Endocrinology, Nuclear Medicine and Medical Physics: hyperthyroidism cure with a single radioiodine administration was obtained in 53% of patients. This outcome raised up to 89% when a higher radiation dose to the target (200- 250 Gy) was prescribed, although the administered activities were still lower, as a rule, than the most commonly employed fixed activities (400-600 Mega-Becquerel--MBq). Our method showed a high level of individual dose optimisation, particularly when compared to simplified methods. In conclusion, the protocol adopted in this study ensures a satisfactory rate of hyperthyroidism cure, while administering quite low 131I activities, provided that an adequate committed radiation dose to the thyroid is prescribed. In this context, the dose indication given by the aforementioned guidelines should probably be revised.

Thyrotropin receptor autoantibody measurement following radiometabolic treatment of hyperthyroidism: comparison between different methods.

BACKGROUND: TSH receptor antibodies (TRAb) play a crucial role in the pathogenesis of Graves' disease (GD). The use of human recombinant TSH-receptor far improved the analytical performance of TRAb assays (2nd-generation assays). The 3rd-generation assay is based on the inhibition of binding of a human biotin-labeled monoclonal thyroid- stimulating antibody (M22) to TSH-receptor by the autoantibodies present in the serum. AIM: We aimed to assess the ability of the 2nd- and 3rd-generation assays to detect serum TRAb following radioiodine therapy for hyperthyroidism. METHODS: Sera from 47 hyperthyroid (25 autoimmune, 22 non-autoimmune) patients were tested using the two different assays before and at different time intervals after radioiodine therapy. The modifications of TRAb were evaluated, as well as the correlation between the two methods. RESULTS: The results obtained by the two methods proved to be closely correlated. A rise in TRAb was invariably observed in GD patients following radioiodine, with a median peak at 6 months, irrespective of their initial clinical status, presence of ophthalmopathy, smoking habits or other variables. Such a rise was nearly superimposable using both methods. No TRAb appearance was observed in patients with non-autoimmune hyperthyroidism. CONCLUSIONS: The use of methods of higher sensitivity with respect to that formerly used indicate that nearly all GD patients develop TRAb following radioiodine, and that this phenomenon is transient and not related to baseline conditions and clinical outcome/efficacy of treatment.

p-cresol methylhydroxylase from a denitrifying bacterium involved in anaerobic degradation of p-cresol.

A bacterium, strain PC-07, previously isolated as part of a coculture capable of growing on p-cresol under anaerobic conditions with nitrate as the acceptor was identified as an Achromobacter sp. The first enzyme of the pathway, p-cresol methylhydroxylase, which converts its substrate into p-hydroxybenzyl alcohol, was purified. The enzyme had an Mr of 130,000 and the spectrum of a flavocytochrome. It was composed of flavoprotein subunits of Mr 54,000 and cytochrome subunits of Mr 12,500. The midpoint redox potential of the cytochrome was 232 mV. The Km and kcat for p-cresol were 21 microM and 112 s-1 respectively, and the Km for phenazine methosulfate, the artificial acceptor used in the assays, was determined to be 1.7 mM. These properties place the enzyme in the same class as the p-cresol methylhydroxylases from aerobically isolated Pseudomonas spp.

Anaerobic biodegradation ofPara-cresol under three reducing conditions.

The anaerobic degradation ofp-cresol was studied with one sediment source under three reducing conditions-denitrifying, sulfidogenic, and methanogenic. Loss ofp-cresol (1 mM) in all the anaerobic systems took initially 3 to 4 weeks. In acclimated culturesp-cresol was degraded in less than a week.p-Cresol was completely metabolized under denitrifying, sulfidogenic, and methanogenic conditions, with formation of nitrogen gas, loss of sulfate, and formation of methane and carbon dioxide, respectively.p-Cresol metabolism proceeded throughp-hydroxybenzal-dehyde andp-hydroxybenzoate under denitrifying and methanogenic conditions. These compounds were rapidly degraded in cultures acclimated top-cresol under all three reducing conditions. These results suggest that the initial pathway ofp-cresol degradation is the same under denitryfying, sulfidogenic, and methanogenic conditions and proceeds via oxidation of the methyl substituent top-hydroxybenzaldehyde andp-hydroxybenzoate. The initial rate ofp-hydroxybenzaldehyde degradation was high in both the unacclimated cultures and in the cultures acclimated top-cresol, suggesting that this step is nonspecific. Benzoate was additionally detected as a metabolite followingp-hydroxybenzoate in the methanogenic cultures, but not in the denitrifying or sulfidogenic cultures. The degradation pathway therefore may diverge afterp-hydroxybenzoate formation depending on which electron acceptor is available.

Anaerobic oxidation of p-cresol mediated by a partially purified methylhydroxylase from a denitrifying bacterium.

Anoxic cell extracts of a denitrifying bacterial isolate (PC-07) were shown to oxidize p-cresol to p-hydroxybenzoate. Oxidation of the substrate was independent of molecular oxygen and required nitrate as the natural terminal electron acceptor. Two enzyme activities were implicated in the pathway utilized by PC-07. A p-cresol methylhydroxylase mediated the oxidation of p-cresol to p-hydroxybenzaldehyde, which was further oxidized to p-hydroxybenzoate by an NAD+-dependent dehydrogenase. The PC-07 methylhydroxylase was partially purified by anion-exchange chromatography. The protein appeared to be a multifunctional flavocytochrome, which first oxidized p-cresol to p-hydroxybenzyl alcohol, which was then oxidized to p-hydroxybenzaldehyde. The identity of the aldehyde was confirmed by mass spectroscopy. The PC-07 methylhydroxylase had a limited substrate range and required an alkyl-substituted phenolic ring with a hydroxyl group in the para position. From the available evidence, p-cresol, a naturally occurring phenol, exhibited the greatest affinity to the enzyme and therefore may be its natural substrate.

Anaerobic oxidation of p-cresol by a denitrifying bacterium.

Metabolism of p-cresol (pCr) under nitrate-reducing conditions is mediated by the denitrifying bacterial isolate PC-07. The methyl substituent of the substrate is oxidized anaerobically by whole-cell suspensions of PC-07 through a series of dehydrogenation and hydration reactions to yield p-hydroxybenzoate (pOHB) in stoichiometric proportions. The partially oxidized intermediates in the pathway p-hydroxybenzyl alcohol and p-hydroxybenzaldehyde can also serve as substrates for pOHB formation. Nitrate is required as the external electron acceptor and is reduced to molecular N2. Reduction of the nitrate is stoichiometric, with pCr serving as the electron donor. In addition, the molar relationship between the electron acceptor (NO3-) reduced to the electron donor oxidized decreased to approximately 2:3 and then to 1:3 when p-hydroxybenzyl alcohol or p-hydroxybenzaldehyde, respectively, served as substrates. The decreased ratios were to be expected when the partially oxidized intermediates served as substrates, because they provided correspondingly less reducing power for pOHB formation. The anaerobic oxidation of pCr by PC-07 demonstrates a mechanism whereby aromatic compounds can be transformed in anoxic environments.

Enzymatic aryl-o-methyl-C labeling of model lignin monomers.

Aryl-O-methyl ethers are abundant in aerobic and anaerobic environments. In particular, lignin is composed of units of this type. Lignin monomers specifically radiolabeled in methoxy, side chain, and ring carbons have been synthesized by chemical procedures and are important in studies of lignin synthesis and degradation, humus formation, and microbial O-demethylation. In this paper attention is drawn to an enzymatic procedure for preparing O-methyl-C-labeled aromatic lignin monomers which has not previously been exploited in microbial ecology and physiology studies and which has several advantages compared with chemical synthesis procedures. O-[methyl-C]vanillic and O-[methyl-C]ferulic acids were prepared with S-[methyl-C]adenosyl-l-methionine as the methyl donor, using commercially obtained porcine liver catechol-O-methyltransferase (EC 2.1.1.6). The specific activity of the methylated products was the same as that of the methyl donor, a maximum of about 58 muCi/mumol, and the yields were 42% (vanillate) and 35% (ferulate). Thus lignin monomers are readily prepared as O-methylated products of the catechol-O-methyltransferase reaction and, with this enzyme method of preparation, would be more widely available than labeled compounds which require chemical synthesis.

Fate of hydrocarbons during oily sludge disposal in soil.

A 1,280-day laboratory simulation of the "landfarming" process explored the fate in soil of polynuclear aromatics (PNAs) and total extractable hydrocarbon residues originating from the disposal of an oily sludge. In addition to the measurement of CO(2) evolution, periodic analyses of PNAs and hydrocarbons monitored biodegradation activity. The estimation of carbon balance and of soil organic matter assessed the fate of residual hydrocarbons. Seven sludge applications during a 920-day active disposal period were followed by a 360-day inactive "closure" period with no further sludge applications. A burst of CO(2) evolution followed each sludge addition, but substantial amounts of undegraded hydrocarbons remained at the end of the study. Hydrocarbon accumulation did not inhibit biodegradation performance. Conversion of hydrocarbons to CO(2) predominated during active disposal; incorporation into soil organic matter predominated during the closure period. In this sludge, the predominant PNAs were degraded more completely (85%) than total hydrocarbons. Both biodegradation and abiotic losses of three- and four-ring PNAs contributed to this result. Some PNAs with five and six rings were more persistent, but these constituted only a small portion of the PNAs in the sludge. The study confirmed that the microbially mediated processes of mineralization and humification remove sludge hydrocarbons from soils of landfarms with reasonable efficiency.