Evaluation of 99mTc-UBI 29-41 scintigraphy for specific detection of experimental multidrug-resistant Staphylococcus aureus bacterial endocarditis.

AIM: The aim of this paper was to test the ability of technetium-99m labelled synthetic peptide UBI 29-41 scintigraphy (99mTc-UBI 29-41), composed of the antimicrobial peptide ubiquicidin, specifically targets microorganisms in to discriminate between infected and uninfected endocarditis using a rat model previously validated. METHODS: 99mTc-UBI 29-41 scintigraphy was evaluated for its accumulation in infective endocarditis (IE) with multidrug resistant Staphylococcus aureus (MRSA) performed in an experimental rat model, resembling early endocarditis in humans. Serial planar scintigraphic and biodistribution analysis of infected vegetations are compared to rats with sterile vegetations. Heart-to-lung uptake ratios (T/NT ratios) were calculated in both with in-vivo scintigraphy and in ex vivo tissue samples. RESULTS: Bacterially infected vegetations were already observed at 15 min after injection of 99mTc-UBI 29-41 while no significant uptake was observed in sterile vegetations. Moreover, a good correlation (R2=0.819) was calculated between T/NT ratios of 99mTc-UBI 29-41 and the number of viable MRSA present in the infected vegetation. There was no correlation between the 99mTc-UBI 29-41 uptake and the weight of the vegetations in either case. CONCLUSION: In this experimental study in rats, planar 99mTc-UBI 29-41 scintigraphy permitted early and specific detection of MRSA induced endocarditis. Furthermore, accumulation of the tracer depends on the number of viable MRSA and not on the weight of the vegetation. This proof of principle offers much promise that 99mTc-UBI 29-41 scintigraphy can be a dedicated non-invasive imaging tool for the early detection of infective endocarditis. Finally, this model has to be further evaluated with state-of-the art small imaging modalities.

Combining iodine-131 Lipiodol therapy with low-dose cisplatin as a radiosensitiser: preliminary results in hepatocellular carcinoma.

A prospective pilot trial was performed in 20 patients randomised to receive either (131)I-Lipiodol therapy alone (n=10) or (131)I-Lipiodol combined with a short low-dose cisplatin infusion (n=10), the aim being to evaluate the possible positive influence of a radiosensitiser on toxicity and tumour response. An activity of 1,354-2,128 MBq (mean 1,824 MBq) [36.6-57.5 mCi (mean 49.3 mCi)] (131)I-labelled Lipiodol was administered by selective instillation in the hepatic artery. Cisplatin was given in a dose of 30 mg/m(2) at day -1 and day +6 (day 0: (131)I-Lipiodol). The primary endpoint of this trial was toxicity of therapy; points of secondary interest were tumour response and survival at 6 months. With the use of cisplatin we found a higher percentage of stable or diminished tumour size (90%, vs 40% without). A benefit in group survival at 6 months was not evident. Low-grade stomatitis in one patient and minor changes in peripheral blood count were probably directly related to cisplatin, but its administration is unlikely to be associated with an excess of serious side-effects. The use of low-dose cisplatin infusion as a radiosensitising agent in (131)I-Lipiodol therapy for hepatocellular carcinoma seems safe and may be beneficial for tumour control. Larger patient groups are necessary for confirmation and to establish the future role of (131)I-Lipiodol in hepatocellular carcinoma.

Promising role of 18-F-fluoro-D-deoxyglucose positron emission tomography in clinical infectious diseases.

18-F-fluoro-D-deoxyglucose positron emission tomography (FDG PET) has become an established imaging tool in clinical oncology, cardiology and neurology and is now entering the field of clinical infectious diseases. The purpose of this article is to review the currently available, albeit limited, literature on FDG PET in the diagnosis of various infections and fever of unknown origin. Those indications for which FDG PET offers added value over more available techniques like labelled leucocyte scanning, gallium scanning and magnetic resonance imaging are especially highlighted. FDG PET seems to have an incremental value in the assessment of chronic osteomyelitis, especially in the axial skeleton, as well as in the diagnostic workup of fever of unknown origin and HIV complications. Cost-effectiveness studies are needed to define its place in the current diagnostic strategies of these pathologies.

Recombinant humane thyrotropin (rhtSH) a new aid in the diagnosis and treatment of thyroid carcinoma with radio-iodine.

By example of two cases a newly available tool, the recombinant humane thyroid stimulating hormone (rhTSH) is discussed in its use as an adjunct in diagnosing and treating differentiated thyroid carcinoma with radio-iodine. This product is an easier and safe alternative to the necessary rise of TSH induced by thyroid hormone withdrawal and concurrent hypothyroidism. Although discrepancies in favour of the classical approach have been demonstrated in some patients, the clinical relevancy of these must be weighted against the advantage of avoiding undesirable symptoms and possible tumour growth by the use of rhTSH. The role of rhTSH in the follow-up diagnosis and radioiodine treatment of thyroid carcinoma will undoubtedly increase in importance.

Repetitive analyses of P-glycoprotein in chronic myeloid leukaemia.

P-glycoprotein, a pump located in the plasma cell membrane, extrudes several clinically important drugs from the cell, and hence causes multidrug resistance. Reversing clinical drug resistance is possible by using agents that inhibit the activity of P-glycoprotein. We describe the results of sequential flow cytometric determinations of P-glycoprotein expression and activity in two patients suffering from acute lymphoblastic transformation of chronic myeloid leukaemia. Neither P-glycoprotein expression, nor its activity could be detected in the initial sample of the first patient. In the second patient, no P-glycoprotein expression was found at diagnosis. However, after chemotherapy containing P-glycoprotein substrates, a significant expression was found in both patients and the functional flow cytometric test was positive. In order to achieve an accurate selection of patients that might benefit from the clinical use of P-gp inhibitors, repeated analyses are indicated in each patient suffering from acute leukaemia, during the course of the illness.