Impact of antagonistic yeasts from wine grapes on growth and mycotoxin production by Alternaria alternata.

AIMS: Alternaria alternata is a major contaminant of wine grapes, meaning a health risk for wine consumers due to the accumulation of toxic metabolites. To develop a successful biofungicide, the effectiveness of epiphytic wine grape yeasts against A. alternata growth and toxin production was assessed in vitro under temperature and aW conditions that simulate those present in the field. METHODS AND RESULTS: The effect of 14 antagonistic yeasts was evaluated on growth and alternariol (AOH), alternariol monomethyl ether (AME) and tenuazonic acid (TA) production by three A. alternata strains in a synthetic medium with composition similar to grape (SN) at three temperatures (15, 25 and 30°C). All Metschnikowia sp. yeast strains evaluated completely prevented A. alternata growth and mycotoxin production at all temperatures in SN medium. Meanwhile, the growth inhibition exerted by Starmerella bacillaris yeast strains was higher at 30°C, followed by 25 and 15°C, being able to show a stimulating or inhibiting effect. Hanseniaspora uvarum yeast strains showed a growth promoting activity higher at 15°C, followed by 25 and 30°C. Even at conditions where A. alternata growth was stimulated by the S. bacillaris and H. uvarum yeasts, high inhibitions of mycotoxin production (AOH, AME and TA) were observed, indicating a complex interaction between growth and mycotoxin production. CONCLUSION: There is a significant influence of temperature on the effectiveness of biocontrol against A. alternata growth and mycotoxin production. Metschnikowia sp. strains are good candidates to compose a biofungicide against A. alternata. SIGNIFICANCE AND IMPACT OF THE STUDY: Among the different antagonistic yeasts evaluated, only Metschnikowia sp. strains were equally effective reducing A. alternata growth and mycotoxin at different temperatures underlining the importance of considering environmental factors in the selection of the antagonists.

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.

Water activity and temperature effects on growth and mycotoxin production by Alternaria alternata strains isolated from Malbec wine grapes.

AIMS: To study the effects of water activity (aW ; 0·99, 0·98, 0·97, 0·96 and 0·95), temperature (15, 25 and 30°C), incubation time (7-28 days), and their interactions on mycelial growth and alternariol (AOH), alternariol monomethyl ether (AME) and tenuazonic acid (TA) mycotoxin production on a synthetic nutrient (SN) media similar to grape composition by three strains of Alternaria alternata isolated from wine grapes from Argentina. METHODS AND RESULTS: Interacting conditions of aW , temperature and time of incubation were used to examine growth and mycotoxin production. All strains were able to grow at 0·95 aW , but maximum growth rates were obtained at 0·99 aW and 25°C. Maximum levels of AOH, AME and TA were obtained at 0·99 aW and 25°C, but high amounts of TA were also obtained at 0·96 aW and 15 or 30°C. Production of AOH and AME was favoured over TA at 25°C. TA levels were more sustained than AOH and AME. CONCLUSION: The optimum and marginal conditions for growth and mycotoxin production by A. alternata on a SN media similar to grape composition were in agreement, but certain stressful conditions for growth evaluated also promote mycotoxin production. SIGNIFICANCE AND IMPACT OF THE STUDY: Temperature and aW conditions that allows growth and mycotoxin production are those normally found during wine grape ripeness in the field. Therefore, efforts should be made to prevent Alternaria presence and mycotoxin production in wine grapes.

Gene transcript analysis blood values correlate with 68Ga-DOTA-somatostatin analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease status.

PURPOSE: Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between (68)Ga-somatostatin analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. METHODS: We utilized two independent patient groups with positive (68)Ga-SSA PET: data set 1 ((68)Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 ((68)Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUVmax), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. RESULTS: SUVmax measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ(2) = 20.1, p < 2.5×10(-6)). The majority (78 %) had Ki-67 < 20 %. Gene transcript scores were predictive of imaging with >95 % concordance and significantly correlated with SUVmax (R (2) = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUVmax. Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUVmax [ROC-derived AUC (R (2) = 0.7, p < 0.05)]. No statistical relationship was identified between CgA and Ki-67 and no relationship with imaging parameters was evident. CONCLUSION: (68)Ga-SSA PET imaging parameters (SUVmax) correlated with a circulating NET transcript signature. Disease status could be predicted by an elevated quotient of gene expression (MORF4L2) and SUVmax. These observations provide the basis for further exploration of strategies that combine imaging parameters and disease-specific molecular data for the improvement of NET management.

Highly cold-active pectinases under wine-like conditions from non-Saccharomyces yeasts for enzymatic production during winemaking.

UNLABELLED: The influence of oenological factors on cold-active pectinases from 15 preselected indigenous yeasts belonging to Aureobasidium pullulans, Filobasidium capsuligenum, Rhodotorula dairenensis, Cryptococcus saitoi and Saccharomyces cerevisiae was investigated. Pectinolytic enzymes were constitutive or partially constitutive; and high glucose concentration (200 g l(-1) ) did not affect or increased pectinase production at 12°C and pH 3·5 (up to 113·9 U mg(-1) ) only in A. pullulans strains. SO2 (120 mg l(-1) ) slightly affected the growth of A. pullulans strains but did not affect pectinase production levels. Ethanol (15%) barely affected pectinase activity of A. pullulans strains but diminished relative activity to 12-79% of basidiomycetous yeasts. Moreover, non-Saccharomyces strains showed promising properties of oenological interest. This study demonstrates that cold-active pectinases from some A. pullulans strains were able to remain active at glucose, ethanol and SO2 concentrations usually found in vinification, and suggests their potential use as processing aids for low-temperature winemaking. SIGNIFICANCE AND IMPACT OF THE STUDY: Nowadays, there is increasing interest in low-temperature winemaking. Nevertheless, commercial oenological pectinases, produced by fungi, are rarely active at low temperatures. Cold-active pectinases that are stable under vinification conditions are needed. This study indicated that cold-active and acid-tolerant pectinases from non-Saccharomcyes yeasts were able to remain active at glucose, ethanol and SO2 concentrations usually found in winemaking. Furthermore, not only are these yeasts a source of cold-active pectinases, but the yeasts themselves are also potential adjunct cultures for oenology to produce these enzymes during cold-winemaking.

A case of Leishmania infection with focal splanchnic involvement without systemic symptoms: a potential anti-inflammatory role for vitamin D.

CASE REPORT: We report the case of a 59 year-old woman with persistent nausea, hyporexia, fatigue and mild abdominal discomfort. The patient was hospitalized upon suspicion of malignancy due to multiple hepatic and splenic nodules found on an abdominal ultrasound. Hypercalcemia emerged at initial diagnostic workup, which was considered secondary to iatrogenic vitamin D intoxication. After an adequate management of hypercalcemia and normalization of serum calcium level, all symptoms presented by the patient completely regressed. In order to characterize splanchnic lesions, several biochemistry, microbiology and radiological tests were performed, including two bioptic specimens of a focal hepatic lesion. Eventually, a diagnosis of leishmanial infection was made. The patient started a specific anti-leishmanial treatment, and the focal hepatic and splenic lesions progressively disappeared. CONCLUSION: To our knowledge, this is the first reported case of asymptomatic leishmanial infection with a widespread focal splanchnic involvement. The anti-inflammatory effect of vitamin D could be related to this atypical presentation of visceral leishmaniasis without systemic symptoms.

Excimer laser technology in percutaneous coronary interventions: Cardiovascular laser society's position paper.

Excimer Laser Coronary Atherectomy (ELCA) is a well-established therapy that emerged for the treatment of peripheral vascular atherosclerosis in the late 1980s, at a time when catheters and materials were rudimentary and associated with the most serious complications. Refinements in catheter technology and the introduction of improved laser techniques have led to their effective use for the treatment of a wide spectrum of complex coronary lesions, such as thrombotic lesions, severe calcific lesions, non-crossable or non-expandable lesions, chronic occlusions, and stent under-expansion. The gradual introduction of high-energy strategies combined with the contrast infusion technique has enabled us to treat an increasing number of complex cases with a low rate of periprocedural complications. Currently, the use of the ELCA has also been demonstrated to be effective in acute coronary syndrome (ACS), especially in the context of large thrombotic lesions.

Conventional and novel PET tracers for imaging in oncology in the era of molecular therapy.

In the last ten years, the development of several novel targeted drugs and the refinement of state of the art technologies such as the genomics and proteomics and their introduction to clinical practice have revolutionized the management of patients affected by cancer. However, everyday practice points out several clinical questions: the difficulty of response assessment to new drugs especially using standard RECIST criteria that do not provide information on biological, vascular or metabolic variations; the inadequate selection of patients who are likely to benefit from a targeted therapy excluding those with breast cancer and gastrointestinal stromal tumours; the need to know the global biological background of diseases especially in metastatic setting using repeatable non-invasive procedures. Molecular imaging could provide information on in vivo distribution of biological markers in response to targeted therapy and could improve the selection of patients before therapies. The aim of this review is to analyze the current role of conventional and innovative positron emission tomography (PET) radiotracers in clinical practice and to explore the promising perspectives of molecular imaging in cancer research.

18F-FDG small animal PET for early detection of human anaplastic large cells lymphoma xenograft in immunocompromised mice.

The purpose of the present study was to assess if small animal PET is useful for serially monitoring the development of a human anaplastic large cell lymphoma (ALCL) murine xenograft and for the early selection of tumour bearing animals. The human ALCL Karpas 299 cell line was subcutaneously injected in 6-week-old NOD/SCID (non-obese diabetic/NCrCrl- Prkdc) mice (10(7) cells/mouce in 150 pil FBS) at the right flank level. Small animal 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was serially performed (intravenous injected dose: 20 MBq in < 0.15 ml, uptake time: 60 min, image acquisition: 1 bed position of 15 min): early PET at 2 days after cell inoculation in 4/8 mice and at 4 days in the remainig 4/8, later PET scans were performed in all the animals at 7, 14, 21 and 28 days after inoculation. The images were evaluated visually and the tumour to background ratio (TBR) was used for semiquantitative analysis. Pathology sections were obtained in all cases. PET detected the presence of the tumour as early as seven days after inoculation in 4/8 mice and at 14 days in 2/8. Of the two remaining mice, one died after the first PET scan (thus preventing any evaluation of detection time) while the other showed a microscopic neoplastic infiltration at tracheal level at autopsy. Mean TBR progressively increased in all positive cases, particularly in the first 3 weeks, reaching a plateau afterwards. PET was positive in 6/8 (75%) animals, detecting the presence of viable tumour cells earlier than macroscopic evaluation, thus may be used for the early identification of tumour bearing animals.

Current status of PET imaging of neuroendocrine tumours ([18F]FDOPA, [68Ga]tracers, [11C]/[18F]-HTP).

Neuroendocrine neoplasms (NEN) functional imaging is an evolving field that witnessed major advances in the past two decades. The routine use of PET/CT with an array of new radiotracers to specifically study NEN resulted in an increase in lesions detection. Currently, PET radiopharmaceuticals for NEN imaging include both metabolic ([18F]DOPA, [18F]FDG, [11C]/[18F]-HTP) and receptor-mediated compounds ([68Ga]DOTA-peptides). Discussion is still on-going regarding the clinical setting that may benefit the most from the use of one tracer over the other. [68Ga]DOTA-peptides are accurate for the detection of well differentiated NEN and are increasingly employed. Moreover, providing data on somatostatin receptors expression on NEN cells, they represent a fundamental procedure to be performed before starting therapy, as well as to guide treatment, with either hot or cold somatostatin analogues. The easy and economic synthesis process also favours their clinical employment even in centres without an on-site cyclotron. [18F]DOPA is accurate for studying well differentiated tumours however the difficult and expensive synthesis have limited its clinical employment. It currently can be successfully used for imaging tumours with variable to low expression of SSR (medullary thyroid carcinoma, neuroblastoma, pheocromocytoma), that cannot be accurately studied with [68Ga]DOTA-peptides. [11C]/[18F]-HTP has also been proposed to image well differentiated NEN, on the basis of serotonin pathway activity, for which [11C]/[18F]-HTP can be used as precursor. However, although preliminary data are encouraging, the feasibility of its widespread clinical use is still under discussion, mainly limited by a complex synthesis process and more proven advantages over other currently employed compounds. This review aims to provide an overview of the current status and clinical application of PET tracers to image well differentiated NEN and to focus on the still open-issues of debate.

Digoxin-induced vasoconstriction of normal and atherosclerotic epicardial coronary arteries.

This study evaluated the effect of bolus infusion of digoxin (0.014 mg/kg in 10 minutes, intravenously) on large coronary arteries measured by quantitative digital angiography. Twenty-two patients (mean age +/- standard deviation 47 +/- 12 years) divided into 3 groups were studied. The effects of digoxin infusion (after 10 and 20 minutes) and sublingual administration of isosorbide dinitrate were investigated in group I (patients with angiographically normal coronary arteries, n = 9) and in group II (patients with atherosclerotic coronary arteries, n = 8). To determine whether the effects of digoxin were mediated by activation of alpha-adrenergic receptors, coronary angiography was performed in group III after alpha-adrenoceptor blockade (phentolamine 0.11 mg/kg, intravenously) (n = 5). Ten minutes after the end of digoxin infusion, the cross-sectional area decreased from 7.7 +/- 4.1 to 6.0 +/- 2.2 mm2, and after 20 minutes to 5.6 +/- 2.6 mm2 (p less than 0.05) in group I. Isosorbide dinitrate reverted digoxin-induced vasoconstriction as cross-sectional area increased to 8.5 +/- 3.4 mm2 (p = not significant versus baseline). Twenty minutes after digoxin infusion, heart rate significantly decreased from 79 +/- 16 to 74 +/- 13 beats/min (p less than 0.01). Ten minutes after digoxin infusion, peripheral vascular resistance increased significantly from 1,396 +/- 693 to 1,693 +/- 984 dynes.s.cm-5 (p less than 0.05), whereas cardiac output did not change. Twenty minutes after digoxin infusion, minimal stenosis diameter decreased significantly from 1.6 +/- 0.5 to 1.4 +/- 0.5 mm (p less than 0.05) in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Rationale and design of a multi-center randomized trial of comprehensive geriatric assessment consultation for hospitalized patients in an HMO.

OBJECTIVE: To describe the evaluation of an interdisciplinary comprehensive geriatric assessment (CGA) consultation program for targeted hospitalized patients. DESIGN: Multi-center randomized clinical trial (RCT) at four hospitals where patients were randomly assigned to CGA consultation or usual care by the attending physician, and a non-equivalent control group (NCG) at two hospitals. SETTING: Six hospitals in a multi-specialty group practice model health maintenance organization (HMO). PARTICIPANTS: 3593 patients age 65 years or older meeting at least one of 13 inclusionary criteria at admission. INTERVENTION: Screening by hospital staff and standardized CGA consultation conducted by a nurse practitioner, social worker, and geriatrician at the four RCT hospitals. MAIN OUTCOME MEASURES: Functional and health status, mortality, rehospitalization, and cost-effectiveness of the CGA program at 1 year post-randomization; validation of targeting (inclusionary) criteria that identify subgroups of patients deriving benefit from CGA; and physician contamination (learning from CGA and changing treatment provided to control patients). CONCLUSIONS: A number of methodological issues need to be considered when conducting effectiveness trials of CGA. The concurrent design of a multi-center RCT, coupled with the NCG to determine physician contamination, is an innovative approach intended to determine more precisely the cost-effectiveness of CGA for frail hospitalized elderly persons. The large and heterogeneous patient population and the broad array of inclusionary criteria will permit the evaluation of the benefit of CGA for subgroups. All these features are intended to enhance the generalizability of study results.

Study of adhesion of Lactobacillus casei CRL 431 to ileal intestinal cells of mice.

It is well known that the cell wall of Lactobacillus casei CRL 431, a strain present in probiotics, presents lectinlike surface molecules. Presence of these molecules stimulates the immune system. Given the role that lectins and lectinlike substances play in the adhesion phenomenon, it is probable that this is an initial stage in the immunostimulation produced by this bacterium. To confirm this, adhesion of this microorganism to exfoliated mouse ileal epithelial cells was studied in vitro. Other L. casei strains isolated from adult human intestines and one of dairy origin were also examined for their ability to adhere to ileal epithelial cells. Another strain, which was included in the present study, was Lactobacillus acidophilus CRL 730. L. casei strains isolated from humans showed good ability to adhere to ileal epithelial cells, whereas L. casei isolated from dairy origin did not. Adhesion was only observed at 37 degrees C and at a pH between 6 and 7.5. The exposure time needed for highest adhesion was 30 min. Presence of lectinlike substances on the surface of L. casei CRL 431 is important to this adhesion phenomenon, since adherence capacity was lost after removal of these substances.

Study of the morphology of the cell walls of some strains of lactic acid bacteria and related species.

The objective of the present study was to find an explanation for the biological effect of the bacteria present in a biotherapeutic milk (Lactobacillus casei CRL 431 and Lactobacillus acidophilus CRL 730). The ability of bacterial cell walls to induce an immune response when introduced into an organism is well known. In this paper we specifically analyzed the morphology of these cell walls. Besides the two bacterial strains used in the fermented milk, two other lactic acid bacteria, belonging to another genus and unable to induce an immune system response, as well as a strain of Propionibacterium, of which the immune modulating capacity is known, were used in this work. We found a structural particularly in strains with immunostimulating capacity (L. casei CRL 431 and P. acidopropionici CRL 1198): molecules which protrude from the cell surface. In L. casei CRL 431 these molecules were identified as lectins because they are able to agglutinate yeast cells treated with glutaraldehyde and glycine. The structures protruding from P. acidipropionici CRL 1198 cells were teichoic acids. Teichoic acid and lectin-like structures can participate in adhesion to intestinal cells. The immunostimulation observed can be induced by the adhesion phenomenon.

Gallium-68 DOTANOC imaging in paraganglioma/pheochromocytoma: presentation of sample cases and review of the literature.

Gallium-68 DOTANOC is a high affinity somatostatin receptor ligand, first introduced in 2005 for imaging neuroendocrine tumors. Due to its technically simple production, broad availability, favourable biodistribution and advantageous dosimetry, although not approved yet in all European countries, gallium-68 DOTANOC has rapidly gained acceptance in the diagnostic and therapeutic work-flow of different types of neuroendocrine tumors. Principal indications in clinical practice in countries where it is officially approved include diagnosis and staging, restaging after treatment, identification of sites of unknown primary and selection of patients with neuroendocrine tumors eligible for therapy with somatostatin analogues.

Imaging of NETs with PET radiopharmaceuticals.

Neuroendocrine tumours (NET) diagnosis has represented a major challenge in the past decades. The introduction of somatostatin receptor scintigraphy in the diagnostic work-up led to a significant improvement of accuracy. However with the advent of positron emission tomography (PET) that presents a higher spatial resolution as compared to the gamma camera and an array of different radiotracers, it is now possible to image NET with an even higher accuracy. In fact, PET imaging of NET is a rapidly evolving field closely connected to the development of novel beta-emitting radiopharmaceuticals. NET can be easily visualized on PET scans using an array of both metabolic and receptor-based tracers. [18F]DOPA and [68Ga]DOTA-peptides (DOTA-TOC, DOTA-NOC, DOTA-TATE) are very promising to image well differentiated NET and were reported to be superior to other imaging modalities (computed tomography [CT], somatostatin receptor scintigraphy). On the contrary, the role of [18F]FDG is limited in well differentiated NET, due to their low glucose metabolism and growth rate, while it still can provide valuable information in less differentiated tumours. On-going studies are investigating the potential role of new imaging agents (bombesin, GLP-1, CCK) that specifically bind to receptors expressed on NET cells.

18[F]FDG small animal PET study of sorafenib efficacy in lymphoma preclinical models.

AIM: Kinase inhibitors have been proposed as novel therapeutic agents in different forms of solid tumours. The Food and Drug Administration (FDA) approved the use of Sorafenib, an oral multikinase inhibitor, for advanced renal carcinoma and unresectable hepatocellular carcinoma. On-going studies are investigating the efficacy of Sorafenib in other solid tumours such as melanoma and non-small cells lung carcinoma and pre-clinical models showed the efficacy of treatment with Sorafenib in murine models of renal cells carcinoma, breast cancer, colon carcinoma and melanoma. To our knowledge, Sorafenib has never been employed in human lymphoma. The aim of the present study was to assess the efficacy of Sorafenib in murine models of human anaplastic large cells lymphoma (ALCL) and Hodgkin lymphoma (HD). METHODS: Sorafenib cytotoxicity was assessed in vitro and growth inhibition (IC50) was calculated. Cells were assayed for Caspase-3 to measure apoptosis. Human ALCL and HD xenografts in NOD/SCID mice were monitored by small animal positron emission tomography (PET) and computed tomography (CT) over time. Tumour bearing animals were randomly selected to receive treatment with Sorafenib or no treatment. Pathology was available in all cases. RESULTS: Sorafenib efficacy on cells proliferation and apoptosis (IC50: HD=0.0343 mg/L; ALCL=0.319 mg/L) was confirmed in vitro. Caspase-3 production showed a dose-dependent trend reaching significantly higher values for 0.046 mg/L and 0.465 mg/L drug concentrations in both cell lines. In vivo experiments showed a progressive increase of tumour lesions metabolism and dimensions regardless treatment. CONCLUSION: Sorafenib showed a good cytotoxic effect in vitro especially on human HD cell line, but these findings were not confirmed in vivo. The strong discrepancy between in vitro and in vivo results suggests that further studies are needed to better acknowledge the biodistribution and metabolism of Sorafenib in NOD/SCID mice. Factors influencing drug availability at tumour site or differences in the downstream pathways may be responsible for the scarse effect of treatment.

Dual PET/CT with (18)F-DOPA and (18)F-FDG in metastatic medullary thyroid carcinoma and rapidly increasing calcitonin levels: Comparison with conventional imaging.

BACKGROUND: To evaluate the role of a multi-imaging PET with (18)F-DOPA and (18)F-FDG in comparison with conventional imaging (CI) in recurrent medullary thyroid carcinoma (MTC). METHODS: 18 MTC patients who had thyroidectomy were included; they presented with elevated and rapidly increasing calcitonin levels during follow up. CI had revealed metastatic deposits in 9 patients. Patients were referred to us for a PET/CT with (18)F-DOPA and (18)F-FDG. Histologic/cytologic confirmation of recurrent MTC was obtained in at least one PET-positive lesion in all patients. RESULTS: Foci of abnormal uptake were observed in 15 patients at (18)F-DOPA and in 11 at (18)F-FDG; 8 patients showed the same number of positive lesions with both tracers, 2 showed more lesions on (18)F-FDG, 1 was positive at (18)F-FDG alone and 5 at (18)F-DOPA alone. In 3 patients with a DOPA-positive loco-regional relapse a re-operation with curative intent was offered. SUV(max) values were higher for (18)F-FDG compared to (18)F-DOPA (mean 12.7+/-4.1 vs. 5.5+/-2.1, p<0.05). Calcitonin was higher in PET-positive patients compared to PET negative ones, while no significant differences were observed between (18)F-DOPA and (18)F-FDG positive patients. CONCLUSIONS: In MTC patients with rapidly increasing calcitonin levels during follow up, (18)F-DOPA has a good sensitivity and a complementary role with (18)F-FDG PET/CT in detecting metastatic deposits. In our experience, the sensitivity of a multi-imaging (18)F-DOPA &(18)F-FDG PET/CT approach is greater than that obtained with CI. The higher SUV(max) values found with (18)F-FDG in some patients may reflect more aggressive tumors.