Non-invasive imaging of implanted peritoneal carcinomatosis in mice using PET and bioluminescence imaging.

BACKGROUND: Non-invasive imaging of peritoneal carcinomatosis remains challenging. The aim of this study was to compare positron emission tomography (PET) and bioluminescence imaging (BLI) for the early detection of peritoneal carcinomatosis in a mouse model. METHODS: Female nude mice were inoculated intraperitoneally with 1×10(7) HSC45-M2-luc gastric cancer cells. The cells were stably transfected with the gene coding for firefly luciferase. Tumour development was monitored using PET and BLI and in two subgroups, on days 3 and 4 or on days 6 and 7 after tumour cell inoculation. Tumour nodules found on post mortem examination served as the reference standard for evaluating the images. RESULTS: PET detected 58/82 lesions (sensitivity 71 %). This method detected all (100 %) nodules larger than 6 mm, 88 % of nodules in the range of >2-4 mm, and even 58 % of small nodules measuring only 1-2 mm. BLI identified a total of 40/82 lesions (sensitivity 49 %). The difference between PET and BLI was statistically significant at p < 0.05 (PET/BLI chi-square 8.2). CONCLUSIONS: PET was more sensitive than BLI for the detection of early peritoneal carcinomatosis in our mouse model. The sensitivity of BLI largely depended on the site of the lesions in relation to the imaging device.

18FDG-PET to assess recurrence and long term survival in patients with malignant melanoma.

AIM: To assess the diagnostic and prognostic value of FDG-PET/CT in the follow-up of malignant melanoma in comparison to the serum protein S100B. PATIENTS AND METHODS: A total of ninety patients with either low-risk or high-risk malignant melanoma, respectively, were included in this study. The follow-up of the patients was pursuant with the guidelines of the German Dermatological Association. The diagnostic accuracy and diagnostic power were determined for PET/CT and for the serum protein S100B. RESULTS: In 28 of the 90 patients PET/CT was positive in the follow up, 47 patients had an elevated Serum S100B level. Sensitivity, specificity, PPV and NPV of PET/CT for the total groups of patients were 87%, 93%, 87% and 93%. The corresponding values for the serum protein S100B were 65%, 52%, 43% and 74%, respectively. PET/CT positive patients showed a significantly (p < 0.001) higher risk of melanoma associated death compared to patients with PET/CT negative findings. No statistical significance could be found in the 5 year survival rate between the S100B positive and S100B negative patients. CONCLUSION: PET/CT is suitable to confirm or exclude recurrences and can be used to assess the prognosis in melanoma patients. The diagnostic accuracy and the prognostic power is much higher compared to the serum protein S100B.

Variations of clinical SPECT/CT operations: an international survey.

AIM: This survey gathers information about clinical SPECT/CT operations worldwide to help guide standardization of clinical SPECT/CT imaging. METHODS: An international, web-based survey of SPECT/CT users was initiated in 12/2010 through an e-mail distribution. Users were asked 71 questions related to (A) demographics, (B) SPECT/CT operations/utilization and (C) variations in imaging protocols. RESULTS: Collected responses originated from 117 imaging centers in the Americas (66%), Europe (20%), Asia-Pacific (11%) and the Middle-East (3%), with the majority of responding sites representing public health care institutions (69%). Most sites operate 1-2 SPECT/CT-systems (74%), typically installed in Nuclear Medicine departments (84%) with extensive prior SPECT-only experience (82%). Only 14% of SPECT/CTs are installed in Radiology departments. Clinical SPECT/CT imaging is performed either as routine (51%) or ad-hoc "add-on" procedure (49%) with a high inter-site and inter-examination variability. The main application of the integrated CT is to provide anatomical localization of the tracer uptake rather than to produce contrast-enhanced or other high-quality CT images. Consequently, in only 22% of the sites a CT contrast injector is installed. Only 6% of centers use SPECT/CT devices for stand-alone CT procedures. CONCLUSION: An international survey among clinical SPECT/CT users revealed that SPECT/CT is a not a routine component of nuclear medicine procedures. The majority of the centers responding do not fully utilize the diagnostic potential of the CT components. Significant variations in standard imaging protocols were observed. These findings illustrate the need for training and standardization and underscore the need for revisiting the role of SPECT/CT in diagnostic imaging.

Electrically detected displacement assay (EDDA): a practical approach to nucleic acid testing in clinical or medical diagnosis.

This paper introduces the electrically detected displacement assay (EDDA), a electrical biosensor detection principle for applications in medical and clinical diagnosis, and compares the method to currently available microarray technologies in this field. The sensor can be integrated into automated systems of routine diagnosis, but may also be used as a sensor that is directly applied to the polymerase chain reaction (PCR) reaction vessel to detect unlabeled target amplicons within a few minutes. Major aspects of sensor assembly like immobilization procedure, accessibility of the capture probes, and prevention from nonspecific target adsorption, that are a prerequisite for a robust and reliable performance of the sensor, are demonstrated. Additionally, exemplary results from a human papillomavirus assay are presented.

Visualisation of metastatic oesophageal and gastric cancer and prediction of clinical response to palliative chemotherapy using 18FDG PET.

AIM: This study assessed the value of (18)F-deoxyglucose positron emission tomography (FDG-PET) for visualisation and early metabolic response assessment in metastatic gastro-oesophageal cancer. PATIENTS, METHODS: Twenty-six patients who were treated for metastatic disease (20 adenocarcinomas, 6 squamous cell cancers) underwent FDG-PET before and two weeks after the onset of palliative chemotherapy with either oxaliplatin + 5-FU/LV or with docetaxel + capecitabine. PET results were validated according to clinical response based on RECIST criteria. RESULTS: Twenty-four tumours (92%) could be visualised by FDG-PET and were also assessable by a second PET scan at 2 weeks. The 2 tumours that were not detectable by PET were both gastric cancers belonging to the non-intestinal subtype according to Lauren. Median time to progression and overall survival were not significantly different for metabolic responders and non-responders (6.3 vs 5.3 months and 14.1 vs 12.5 months, respectively). CONCLUSION: In this heterogeneous study population, FDG-PET had a limited accuracy in predicting clinical response. However, the metabolic response prediction was particularly good in the subgroup of patients with oesophageal squamous cell cancer. Therefore, FDG-PET and assessment of cancer therapy clearly merits further investigation in circumscribed patient populations with metastatic disease.

[18F-FDG-PET in therapy response of esophageal cancer]. / 18F-fDG-PET zur Therapieverlaufskontrolle beim Osophaguskarzinom.

PET imaging with the glucose analog fluorodeoxyglucose (FDG-PET) has been evaluated in several studies to monitor tumor response in patients undergoing chemo- and radiotherapy. The clinical value of FDG-PET for differentiation of residual tumor and therapy induced fibrosis has been documented for esophageal cancer. Furthermore, there are now several reports suggesting that quantitative assessment of therapy induced changes in tumor FDG-uptake may allow prediction of tumor response and patient outcome very early in the course of therapy. This suggests that FDG-PET may be used to identify non-responders early during neoadjuvant chemoradiotherapy allowing for early modifications of the treatment protocol.

[Radiological diagnostics for iatrogenic retained foreign bodies after surgery]. / Belassene Fremdkörper--aus Sicht des Radiologen.

Retention of surgical sponges is rare. They cause either an aseptic reaction without significant symptoms or an exudative reaction which results in early but non-specific symptoms. Even if there are no studies which compare the diagnostic accuracy of the different imaging modalities, CT seems to be the most promising tool to diagnose foreign bodies. However, apart from radio-paque markers there are no specific signs for the existence of surgical sponges in CT. Therefore, an experienced radiologist is needed to differentiate foreign bodies from morphologically quite similar differential diagnoses such as abscess and haematoma.

[Scintigraphic procedures in internal medicine--indications, limits, possibilities]. / Szintigraphische Verfahren in der Inneren Medizin -- Indikationen, Grenzen, Möglichkeiten.

Scintigraphy continues to play an important diagnostic role in internal medicine. Many diagnostic questions can only be answered with scintigraphic methods. The application of specific radiopharmaceutical tracers offers the unique possibility to visualize ongoing functional changes, associated with diseases concerning internal medicine. The diagnostic potential of modern scintigraphic procedures such as PET for internal medicine is not yet sufficiently used and will continue to grow with hybrid systems, such as PET-CT and SPECT-CT.

DNA-arrays with electrical detection: a label-free low cost technology for routine use in life sciences and diagnostics.

Fast and highly parallel DNA analysis are essential for improved biomedical research and development. Currently fluorescence-based methods are state of the art in DNA microarray analysis. The necessity to modify the target DNA with labels is costly, laborious and requires skilled personnel. Moreover, false positive calls from unspecific adsorption are possible and it is difficult to discriminate perfect matching target sequences from those with a single mismatch. In this paper a new and simple electrochemical approach for hybridisation detection without the need of labelling the target DNA is described. The EDDA (Electrically Detected Displacement Assay) method uses a solution of short redox-labelled signalling oligonucleotides (oligonucleotides carrying a covalently attached redox active compound like ferrocene) to characterize the hybridisation state of label-free capture probe DNA immobilised on gold electrodes. The number of capture probes associated with signalling oligonucleotides is determined by chronocoulometry. This technique allows to separate the electrochemical response of capture probe associated signal probes from the response of freely diffusing signalling probes. In the absence of the complementary target sequences the redox-labelled signalling probes at the surface give rise to an instantaneous increase of the detection signal, while freely diffusing signalling probes show a significantly delayed response. Hybridisation with targets complementary to the capture probe displace the loosely associated signalling probes thereby decreasing the instantaneous signal. Besides an introduction to the EDDA technology, data validating the method for biological material will be presented and an outlook to the detection of single nucleotide polymorphisms (SNPs) is given.

[Modern imaging for liver metastases from colorectal tumors]. / Moderne Bildgebung bei Lebermetastasen kolorektaler Tumoren.

Cross-sectional imaging modalities such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and Positron emission tomography (PET)/CT have benefited from rapid technical advances in recent years. In patients with colorectal tumors, multislice CT is the standard technique for preoperative evaluation and follow-up. It is faster than single-slice helical CT and allows for excellent 3D imaging of liver anatomy and tumor volumetry. The most accurate technique for detecting and characterizing focal liver lesions is MRI using state-of-the-art scanners and liver-specific contrast agents and should be used for preoperative evaluation of all possible surgical candidates. Whole-body FDG-PET and PET/CT are most useful in the detection of extrahepatic disease and may alter clinical management in up to 20% of patients by detecting extrahepatic spread of disease.

FDG PET and CT in locally advanced adenocarcinomas of the distal oesophagus. Clinical relevance of a discordant PET finding.

AIM: The incidence of adenocarcinomas of the distal oesophagus (ADE) has dramatically increased in Western countries. The clinical importance of a FDG PET finding discordant with CT was determined in patients with locally advanced ADE. In addition, tumour standardized uptake values (SUV) were correlated with patient survival. PATIENTS, METHODS: 40 consecutive patients were analyzed retrospectively. All patients underwent an attenuation corrected FDG PET scan (neck, chest, abdomen) and contrast enhanced helical CT of the chest and abdomen. PET and CT scans were reviewed independently and concomitantly with respect to metastases in predefined lymph node sites and organs. Any discordance between PET and CT was assessed for clinical relevance. Clinical relevance was defined as a change in the overall therapeutic concept (curative vs. palliative). Follow-up imaging and histological evaluation served as the gold standard. Mean tumour SUVs were determined by 1.5 cm regions of interest placed over the tumour's maximum. RESULTS: When read independently from the CT scan FDG PET indicated a clinically relevant change in tumour stage in 9/40 patients (23%) and a non-relevant change in 11/40 patients (28%). PET was correct in 5/9 patients (56%) with clinically relevant discordances. In 4/9 patients PET was incorrect (3 false positive due to suspicion of M1-lymph nodes or lung metastases, 1 false negative in disseminated liver metastases). With concomitant reading, PET indicated a clinically relevant change in tumour stage in 6/40 patients (15%) and a non-relevant change in 5/40 patients (13%). PET was correct in 5/6 patients (83%) with clinically relevant discordances. The patient with disseminated liver disease remained the single false negative. Overall, the benefit from PET was based on its higher diagnostic accuracy at organ sites. Tumour SUV did not correlate with patient survival. CONCLUSION: About half of discordances between FDG PET and CT are clinically relevant. Concomitant reading of PET and CT is advisable as it reduces the overall rate of discordances and enhances the accuracy of PET in clinical relevant discordances (from 56% to 83%).

[PET/CT for colorectal and hepatic tumors]. / PET-CT bei kolorektalen und Lebertumoren.

This contribution presents clinical and technical aspects of combining positron emission tomography (PET) and computed tomography (CT) for patients with colorectal tumors and characterization of unclear liver foci. In which manner and for which patients combined PET/CT is superior to PET or CT alone is also discussed. PET/CT can fulfil most prerequisites for imaging in pre- and postoperative management of patients with colorectal tumors and best meets the desire for optimal imaging procedures. Some of the disadvantages encountered in frequently employed CT can be overcome by the combination of PET and CT while increasing both sensitivity in detecting lesions and specificity in their characterization. Questions regarding treatment response offer an opportunity for devising novel study concepts and initiating research on new PET tracers. Although few publications are available, we are of the opinion that the combination of functional and anatomical imaging provided by PET/CT can improve both preoperative management and aftercare. To this end, however, optimum cooperation between practitioners of nuclear medicine and radiology is imperative.

Host-guest interactions at self-assembled monolayers of cyclodextrins on gold

We have developed synthesis routes for the introduction of short and long dialkylsulfides onto the primary side of alpha-, beta-, and gamma-cyclodextrins. Monolayers of these cyclodextrin adsorbates were characterized by electrochemistry, wettability studies, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (TOF-SIMS), and atomic force microscopy (AFM). The differences in thickness and polarity of the outerface of the monolayers were measured by electro-chemistry and wettability studies. On average about 70% of the sulfide moieties were used for binding to the gold, as measured by XPS. Tof-SIMS measurements showed that the cyclodextrin adsorbates adsorb without any bond breakage. AFM measurements revealed for beta-cyclodextrin monolayers a quasi-hexagonal lattice with a lattice constant of 20.6 A, which matches the geometrical size of the adsorbate. The alpha-cyclodextrin and gamma-cyclodextrin monolayers are less ordered. Interactions of the anionic guests 1-anilinonaphthalene-8-sulfonic acid (1,8-ANS) and 2-(p-toluidinyl)naphthalene-6-sulfonic acid (2,6-TNS) and the highly ordered monolayers of heptapodant beta-cyclodextrin adsorbates were studied by surface plasmon resonance (SPR) and electrochemical impedance spectroscopy. The SPR measurements clearly showed interactions between a beta-cyclodextrin monolayer and 1,8-ANS. Electrochemical impedance spectroscopy measurements gave high responses even at low guest concentrations (< or = 5 microM). The association constant for the binding of 1,8-ANS (K = 289,000 +/- 13,000M-1) is considerably higher than the corresponding value in solution. (Partial) methylation of the secondary side of the beta-cyclodextrin strongly decreases the binding.

1H and 31P NMR characterisation of a double breast coil for spectroscopic measurements and imaging.

For the first time a double turn breast coil has been described which can be used for 1H imaging, 1H spectroscopy and 31P spectroscopy. The paper describes basic technical features of the coil, coil design, B1 field/excitation field distribution for 1H and 31P, sensitivity, and feasibility for 31P spectroscopic in vivo studies. The main advantage of the double frequency tuneable coil is that 1H imaging for tumor localization and 31P spectroscopy for response control can be done without an additional repositioning of the patient.