Search

We present a combined experimental and theoretical study of the photophysics of 5-benzyluracil (5BU) in methanol, which is a model system for interactions between nucleic acids and proteins. A molecular dynamics study of 5BU in solution through efficient DFT-based hybrid ab initio potentials revealed a remarkable conformational flexibility – allowing the population of two main conformers – as well as specific solute–solvent interactions, which both appear as relevant factors for the observed 5BU optical absorption properties. The simulated absorption spectrum, calculated on such an ensemble, enabled a molecular interpretation of the experimental UV-Vis lowest energy band, which is also involved in the induced photo-reactivity upon irradiation. In particular, the first two excited states (mainly involving the uracil moiety) both contribute to the 5BU lowest energy absorption. Moreover, as a key finding, the nature and brightness of such electronic transitions are strongly influenced by 5BU conformation and the microsolvation of its heteroatoms. [ABSTRACT FROM AUTHOR]

Personal results are presented to illustrate the development of immunoscintigraphy for the detection of cancer over the last 12 years, from the early experimental results in nude mice grafted with human colon carcinoma to the most modern form of immunoscintigraphy applied to patients, using I123 labeled Fab fragments from monoclonal anti-CEA antibodies detected by single photon emission computerized tomography (SPECT). The first generation of immunoscintigraphy used I131 labeled, immunoadsorbent purified, polyclonal anti-CEA antibodies and planar scintigraphy, as the detection system. The second generation used I131 labeled monoclonal anti-CEA antibodies and SPECT, while the third generation employed I123 labeled fragments of monoclonal antibodies and SPECT. The improvement in the precision of tumor images with the most recent forms of immunoscintigraphy is obvious. However, we think the usefulness of immunoscintigraphy for routine cancer management has not yet been entirely demonstrated. Further prospective trials are still necessary to determine the precise clinical role of immunoscintigraphy. A case report is presented on a patient with two liver metastases from a sigmoid carcinoma, who received through the hepatic artery a therapeutic dose (100 mCi) of I131 coupled to 40 mg of a mixture of two high affinity anti-CEA monoclonal antibodies. Excellent localisation in the metastases of the I131 labeled antibodies was demonstrated by SPECT and the treatment was well tolerated. The irradiation dose to the tumor, however, was too low at 4300 rads (with 1075 rads to the normal liver and 88 rads to the bone marrow), and no evidence of tumor regression was obtained. Different approaches for increasing the irradiation dose delivered to the tumor by the antibodies are considered.

We combine fluorescence up-conversion and time correlated single photon counting experiments to investigate the 5-benzyl uracil excited state dynamics in methanol from 100 fs up to several ns. This molecule has been proposed as a model for DNA/protein interactions. Our results show emission bands at about 310 and 350 nm that exhibit bi-exponential sub-ps decays. Calculations, including solvent effects by a mixed discrete-continuum model, indicate that the Franck Condon region is characterized by significant coupling between the excited states of the benzyl and the uracil moieties, mirrored by the short-lived emission at 310 nm. Two main ground state recovery pathways are identified, both contributing to the 350 nm emission. The first 'photophysical' decay path involves a ππ* excited state localized on the uracil and is connected to the ground electronic state by an easily accessible crossing with S0, accounting for the short lifetime component. Simulations indicate that a possible second pathway is characterized by exciplex formation, with partial benzene → uracil charge transfer character, that may lead instead to photocyclization. The relevance of our results is discussed in view of the photoactivated dynamics of DNA/protein complexes, with implications on their interaction mechanisms. [ABSTRACT FROM AUTHOR]

Copyright of SAUSSUREA is the property of Societe Botanique de Geneve and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is considered to be a very useful adjunct to anatomic imaging techniques and is now primarily used for oncological indications. These indications include diagnosis, staging, and therapy monitoring. In this review, we discuss the articles in which FDG-PET is clinically used for monitoring therapy in lung and colorectal tumours, head and neck cancer, sarcoma, and hepatocellular carcinoma. It is found that the amount of FDG uptake strongly correlates with response to therapy: a decrease in FDG uptake after therapy indicates a positive response to therapy. However, this conclusion is based on small numbers of patients, whereas the exact response mechanism is still unknown. Moreover, in these case series, the interval between tumour therapy and FDG-PET, as well as the method of quantification, SUV or tumour-to-non-tumour ratios, differ per study. Finally, dynamic imaging is a recommended technique by some authors, but it is not a standard technique in clinical practice to evaluate tumour therapy. Therefore, further study is required which has to deal with these major issues before it is possible to draw definite conclusions. [ABSTRACT FROM AUTHOR]

The initial enthusiasm for the development of diagnostic and therapeutic studies involving the use of monoclonal antibodies was replaced by scepticism as hopes remained unfulfilled. Against this background one needs to ask whether immunoscintigraphy (IS) serves clinical needs effectively and whether radioimmunotherapy (RIT) has a future. The current review considers these questions by reference to relevant studies. Taking colorectal cancer as an example, an appraisal is offered of the ability of IS to detect disease at an early stage and thereby to reduce mortality, and of the influence of the results of IS on patient management. It is concluded that in a limited number of cases of colorectal cancer and other solid tumors, IS will allow surgery to be performed at a stage where cure is still possible because of its ability to detect early recurrence. Turning to RIT, the results of studies in respect of various tumour types are reviewed, with due attention to reported toxicity. As regards colorectal cancer, no consistent therapeutic effects have been achieved, and myelotoxicity is typically the dose-limiting factor. Thus many questions remain to be answered, regarding antigens to be targeted, fractionation schedule, the use of 'humanised' antibodies, choice of radionuclide and the use of intact immunoglobulins or fragments. These questions are considered. Overall it is concluded that the most promising application of RIT is as adjuvant therapy in patients with minimal residual disease, and a controlled multicentre trial is recommended. The development of more potent radioimmunoconjugates for therapeutic and ultimately diagnostic purposes will contribute to the improvement and development of IS by increasing its potential to influence prognosis. [ABSTRACT FROM AUTHOR]

A murine monoclonal antibody MLS102 recognizes sialosyl-Tn antigen in mucin and immunohistochemically reacts with more than 80% of colorectal cancer tissues. The purpose of this study was to assess the usefulness of this monoclonal antibody for the immunoscintigraphy of colorectal cancer. Planar and SPECT images were obtained on day 2 or day 3 after injection of 2 mg and 74 MBqIn-labeled MLS102 antibody into 17 patients with colorectal cancer. Nine of 11 primary tumors and 4 of 6 locally recurrent tumors were detected. Positive images were obtained in all tumors larger than 4.5×2.7 cm. Three tumors of less than 2.5 cm and 1 recurrent tumor, which was missed by other imaging modalities, were negative. There were no adverse reactions. Human anti-(mouse Ig) antibody developed in 4 patients. Although improvement of detectability for smaller tumors needs to be pursued, the antibody MLS102 is potentially promising for use in immunoscintigraphy of colorectal cancer. [ABSTRACT FROM AUTHOR]

In 14 patients with proven local recurrence of colorectal cancer or metastases in liver and/or lungs, the sensitivity (SE) in detecting tumor sites was estimated in a single-blind study using conventional planar whole body scintigraphy. Nine patients received F(ab′) and five received MAB by intravenous infusion over 30 min with a dose of 40-200 MBq after skin testing and thyroid blocking, scanning was performed 1-7 days later. All but one patient had elevated plasma CEA levels with a mean of 25.5±31.9 ng/ml. The scans were interpreted by two independent observers. In five of the nine patients receiving F(ab′), the tumor site could be visualized, yielding a sensitivity of 55%. No tumor sites were identified with MAB. The highest tumor uptake was recorded in a patient with additional ovarian cancer with the activity accumulating in the ovarian cancer. The optimum time for imaging was 3 or 4 days after injection. There was no correlation between positive imaging and plasma CEA levels which ranged from 1.9 ng/ml to 100 ng/ml in the positive cases. The thyroid uptake on the sixth day was 0.68%±0.2% of the total dose given despite thyroid blocking. Bone uptake of I was also observed, this was mild in four patients, moderate in three but high in one patient, especially on days one to four. Thus, only anti-CEA F(ab′) seem to be of clinical interest for further evaluation in localizing colorectal cancer. Regarding the still low sensitivity of 55%, further improvement can be expected by gaining experience, using more appropriate isotopes such as In and SPECT. The estimated radiation side effects on thyroid and bone marrow are only modest. [ABSTRACT FROM AUTHOR]

To estimate the radiation exposure to surgical personnel caused by intraoperative radioimmunoscintimetry, we measured dose rates at different distances from patients who had been injected with 950 MBq technetium-99m-labelled intact carcinoembryonic antigen (CEA)-specific antibodies (Szintimun CEA, Behring AG Marburg, FRG) for immunoscintigraphy 24 h earlier. At 0.05 m (corresponding to working positions during surgery) we found 2.0-16.0 μSv h (average 6.4), which is similar to results for nuclear medicine staff. Thus, if radioimmunoscintimetry is to become a routine procedure, according to national regulations in some countries of the European Communities surgical personnel might be regarded as professionally exposed to radiation. [ABSTRACT FROM AUTHOR]

Background: The development of treatment modalities for rectal cancer, including local excision, total mesorectal excision and preoperative radiotherapy, has increased the importance of accurate preoperative staging to allow the optimum treatment to be selected. Methods: A literature review was undertaken of methods of preoperative staging of rectal carcinoma and the evidence for each was evaluated critically. Results: Clinical assessment of rectal carcinoma may give an indication of fixity but is not accurate for staging. Endoanal ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), radioimmunoscintigraphy and positron emission tomography have all been used for staging. The extent of tumour spread through the bowel wall (T stage) is most accurately assessed by endoanal ultrasonography, although this technique is poor at assessing tumour extension into adjacent organs for which both CT and MRI are more accurate. No method accurately determines lymph node involvement, but endoanal ultrasonography is the best available. Liver metastases may be assessed by abdominal ultrasonography, CT, MRI and CT portography (with increasing sensitivity and cost in that order). Conclusion: Endoanal ultrasonography is the most effective method of local tumour staging, with the addition of either CT or MRI if adjacent organ involvement is suspected. Abdominal ultrasonography or CT is recommended for routine preoperative assessment of the liver. [ABSTRACT FROM AUTHOR]