Search

Abstract. The distribution of 3-[[sup 123]I]iodo-L-alpha-methyltyrosine ([sup 123]I-3-IMT) in the tumour region of 21 patients with clinically suspected recurrent squamous cell head and neck carcinoma was studied. Single-photon emission tomography (SPET) imaging of the head and neck region was performed 10 min after the injection of 130-170 MBq [sup 123]I-3-IMT using a dual-detector gamma camera. Images were interpreted visually and classified as positive or negative for recurrent disease. In addition, target to background ratios (T/B) were measured using semi-automated region of interest analysis. IMT-SPET results were compared with the data derived from clinicopathological follow-up. IMT-SPET detected recurrent disease in 14 of 15 patients (sensitivity 93%). T/B ratios ranged between 1.5 and 2.4 (mean 1.88). One patient with a small tumour (1.2 cm) had a false-negative result. This is attributed to the limited spatial resolution of the SPET system. Five of six patients were correctly diagnosed to be negative for tumour recurrence. T/B ratios ranged between 1.2 and 1.4 (mean 1.30). In one patient IMT-SPET was positive without evidence of recurrence based on clinicopathological follow up. This finding was probably due to uptake into inflammatory tissue. IMT-SPET appears to be a sensitive tool (93%) for the... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study on radioimmunotherapy and imaging of multiple myeloma (MM) with anti-idiotypic nanobodies.

BACKGROUND AND PURPOSE Nanobodies are promising antigen-binding moieties for molecular imaging and therapeutic purposes because of their favourable pharmacological and pharmacokinetic properties. However, the capability of monovalent nanobodies to reach targets in the CNS remains to be demonstrated. EXPERIMENTAL APPROACH We have assessed the blood-brain barrier permeability of Nb_An33, a nanobody against the Trypanosoma brucei brucei variant-specific surface glycoprotein (VSG). This analysis was performed in healthy rats and in rats that were in the encephalitic stage of African trypanosomiasis using intracerebral microdialysis, single photon emission computed tomography (SPECT) or a combination of both methodologies. This enabled the quantification of unlabelled and 99mTc-labelled nanobodies using, respectively, a sensitive VSG-based nanobody-detection elisa, radioactivity measurement in collected microdialysates and SPECT image analysis. KEY RESULTS The combined read-out methodologies showed that Nb_An33 was detected in the brain of healthy rats following i.v. injection, inflammation-induced damage to the blood-brain barrier, as in the late encephalitic stage of trypanosomiasis, significantly increased the efficiency of passage of the nanobody through this barrier. Complementing SPECT analyses with intracerebral microdialysis improved analysis of brain disposition. There is clear value in assessing penetration of the blood-brain barrier by monovalent nanobodies in models of CNS inflammation. Our data also suggest that rapid clearance from blood might hamper efficient targeting of specific nanobodies to the CNS. CONCLUSIONS AND IMPLICATIONS Nanobodies can enter the brain parenchyma from the systemic circulation, especially in pathological conditions where the blood-brain barrier integrity is compromised. [ABSTRACT FROM AUTHOR]

Background: Carrier-added [(123)I]-2-iodo-D-phenylalanine (CA [(123)I]-2-I-D-Phe) was previously found to have a preferential retention in tumors with a high tumor background contrast in animal models. A previous human dosimetry study demonstrated a favorable biodistribution and radiation burden in human subjects. Aim: The aim of this study was to investigate the potential of CA [(131)I]-2-I-D-Phe as an agent for radionuclide therapy. Methods: Sixty (60) nude athymic mice were inoculated subcutaneously with firefly luciferase-transduced R1M rhabdomyosarcoma cells. The mice in the therapy group were injected intravenously (i.v.) with 148 MBq [(131)I]-2-I-D-Phe (432 GBq/mmol) in kit solution. Controls were injected with kit solution without radioactivity, with physiological saline, or with 148 MBq [(131)I](-) in physiological saline. Tumor growth was quantified using bioluminescent imaging and caliper measurements. Results: [(131)I]-2-I-D-Phe clearly reduced tumor growth in the treated mice compared with the control groups. A tumor growth-rate reduction of at least 33% was found for mice receiving a therapeutic dose. There were no serious adverse side-effects of the therapy. Conclusions: In conclusion, i.v. injection of CA 148 MBq [(131)I]-2-I-D-Phe specifically reduces tumor growth in athymic nude mice without relevant side-effects on the animals' health. [ABSTRACT FROM AUTHOR]

Abstract: In small animals studies, sick animals often have a significant reduction in heart rate while under anesthesia. The influence of heart rate reduction on Doppler myocardial imaging (DMI) parameters is not known. The aim of the present study was to assess the effect of heart rate reduction on DMI parameters in a small animal model. Twenty-four rats underwent transthoracic echocardiography at baseline and during the administration of ivabradine IV. In all rats, left ventricular (LV) systolic velocity, strain and strain rate were measured in the anteroseptal and inferolateral wall segments from short axis views. In 12 rats (group A), M-mode analysis was also performed for assessment of global LV function. In the other 12 rats (groups B), contractility was quantified invasively using the end-systolic pressure-volume relation (ESPVR) and the preload recruitable stroke work (PRSW). During ivabradine, administration heart rate decreased by 18% in group A (p < 0.001) and 36% in group B (p < 0.001). There was a slight increase in LVEDD and LVESD, with no change in cardiac output or LV ejection fraction. During ivabradine administration, DMI parameters did not change significantly in any group. No significant correlation between DMI parameters and heart rate (r2 = 0.05) or ejection time (r2 = 0.14) could be found. The absence of changes in contractility was confirmed by the absence of change in PRSW and end-systolic elastance (Ees). In conclusion, moderate heart rate reduction did not influence DMI measurements in this specific rat model. Therefore, in the interpretation of DMI data when performing small animal studies, moderate heart rate reduction does not need to be taken into account. (E-mail: igwsc@uzbrussel.be) [Copyright &y& Elsevier]

[125I]-2-iodo-L-phenylalanine, a new radioiodinated phenylalanine analog was evaluated as a potential specific tumor tracer for SPECT. The tracer is obtained with an overall radiochemical yield of at least 98%, a purity of >99%, and a specific activity of 11 MBq/mmol in one pot Kit conditions using the Cu 1+ assisted isotopic exchange. The tracer is evaluated in vitro using R1M rat rabdomyosarcoma cells in HEPES buffer with and without Na+ ions and in MEM buffer. The uptake of [125I]-2-iodo-L-phenylalanine follows a reversible pseudo-first-order reaction which is the same in presence and absence of Na+ ions, but the compound is not incorporated into the cell proteins. The reversible uptake is proven to occur with the same affinity as L-henylalanine by a saturable transport system which is competitively inhibited by BCH, an L transport type selective molecule. Trans-stimulation of the efflux by BCH and typical L transported amino acids shows that the transporter is of the antiport type and fulfils all the properties of the LAT1 heterodimer transport system. [125I]-2-iodo-L-phenylalanine is thus a phenylalanine analog that for the uptake uses for the major part the LAT1 transport system which is known to be over-expressed in tumor cells. This, together with the easy Kit preparation, makes [123I]-2-iodo-L-phenylalanine a promising tumor specific tracer for SPECT. [Copyright &y& Elsevier]