Publications (67) View all
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Article: Synthesis, radioiodination and in vivo screening of novel potent iodinated and fluorinated radiotracers as melanoma imaging and therapeutic probes.
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ABSTRACT: In order to develop new iodinated and fluorinated matched-pair radiotracers for Single-Photon Emission Computed Tomography (SPECT)/Positron Emission Tomography (PET) imaging and targeted radionuclide therapy of melanoma, we successfully synthesized and radiolabelled with iodine-125 seven new derivatives, starting from our previously described lead structure 3. The relevance of these radiotracers for gamma scintigraphic imaging of melanoma in rodent was assessed. The tumoural radioactivity uptake was most often high and specific even at early time points (12.1-18.3% ID/g at 3 h p.i. for [(125)I]39-42) and a fast clearance from the non-target organs was observed. Also, calculated effective doses that could be delivered to tumours when using corresponding [(131)I]-labelled analogues were generally higher than 100 cGy/MBq injected (98.9-150.5 cGy/MBq for [(131)I]39-42). These results make compounds 39-42 suitable candidates for (i) PET imaging of melanoma after labelling with fluorine-18 and (ii) targeted radionuclide therapy of disseminated melanoma after labelling with iodine-131.European journal of medicinal chemistry 03/2013; 63C:840-853. · 3.27 Impact Factor -
Article: In vivo scintigraphic imaging of proteoglycans.
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ABSTRACT: In this chapter, we present the methods developed in our lab for the scintigraphic imaging and direct quantitative evaluation of proteoglycan (PG) distribution in vivo. These methods relate to (1) the synthesis and radiolabeling of the NTP 15-5 with (99m)Tc, (2) preclinical scintigraphic imaging using laboratory animals, and (3) quantitative analysis of scintigraphic images.Methods in molecular biology (Clifton, N.J.) 01/2012; 836:183-98. -
Article: Evaluation of new iodinated acridine derivatives for targeted radionuclide therapy of melanoma using 125I, an Auger electron emitter.
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ABSTRACT: The increasing incidence of melanoma and the lack of effective therapy on the disseminated form have led to an urgent need for new specific therapies. Several iodobenzamides or analogs are known to possess specific affinity for melanoma tissue. New heteroaromatic derivatives have been designed with a cytotoxic moiety and termed DNA intercalating agents. These compounds could be applied in targeted radionuclide therapy using (125)I, which emits Auger electrons and gives high-energy, localized irradiation. Two iodinated acridine derivatives have been reported to present an in vivo kinetic profile conducive to application in targeted radionuclide therapy. The aim of the present study was to perform a preclinical evaluation of these compounds. The DNA intercalating property was confirmed for both compounds. After radiolabeling with (125)I, the two compounds induced in vitro a significant radiotoxicity to B16F0 melanoma cells. Nevertheless, the acridine compound appeared more radiotoxic than the acridone compound. While cellular uptake was similar for both compounds, SIMS analysis and in vitro protocol showed a stronger affinity for melanin with acridone derivative, which was able to induce a predominant scavenging process in the melanosome and restrict access to the nucleus. In conclusion, the acridine derivative with a higher nuclear localization appeared a better candidate for application in targeted radionuclide therapy using (125)I.Investigational New Drugs 12/2011; 29(6):1253-63. · 3.36 Impact Factor -
Article: First ex vivo study demonstrating that 99mTc-NTP 15-5 radiotracer binds to human articular cartilage.
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ABSTRACT: Preclinical data pointed to (99m)Tc-NTP 15-5 as a good candidate for single photon emission computed tomography (SPECT) imaging of cartilaginous disease. We set out to investigate and quantify (99m)Tc-NTP 15-5 ex vivo uptake by human articular cartilage relative to bone (99m)Tc-hydroxymethylene diphosphonate (HMDP) radiotracer. Three osteoarthritic human tibial plateaux and four tibiofemoral joints were incubated with (99m)Tc-NTP 15-5 and (99m)Tc-HMDP for 2 h. Affinity of tracers for cartilage was determined by visual analysis of SPECT/CT acquisitions and measurement of cartilage to cortical bone uptake ratios. Cartilage to cortical bone uptake ratios were 3.90 ± 2.35 and 0.76 ± 0.24, respectively, for (99m)Tc-NTP 15-5 and (99m)Tc-HMDP radiotracers. Visual analysis of fused SPECT/CT slices showed selective, intense (99m)Tc-NTP 15-5 accumulation in articular cartilage, whereas (99m)Tc-HMDP binding was low. Interestingly, a cartilage defect visualized on CT was clearly associated with focal decreased uptake of (99m)Tc-NTP 15-5. The tracer (99m)Tc-NTP 15-5 is of major interest for human cartilage molecular imaging and could find clinical applications in osteoarthritis staging and monitoring.European Journal of Nuclear Medicine 08/2011; 38(11):2077-82. · 4.53 Impact Factor -
Article: New aldehyde and vinylsulfone proteasome inhibitors for targeted melanoma therapy.
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ABSTRACT: The proteasome is a promising target in cancer therapy. However, it is ubiquitous and its inhibitors cause side effects. To target melanoma cells we synthesized new peptide aldehyde and vinylsulfone inhibitors of the proteasome conjugated to the melanin-targeting ligand (MTL) derived from radiotracer [(123)I]-N-(2-diethylaminoethyl)benzamide ([(123)I]BZA) or [(125)I]-N-(4-dipropylaminobutyl)-4-iodobenzamide ([(125)I]BZ18). Influence on the cytotoxicity of the benzamide alkyl side chain length and the composition of the amino acid sequence was assessed. Among the conjugates evaluated, compound 16 and 22 presented the highest cytotoxicity (IC(50), 0.71 and 0.64 μM respectively), which persisted in the presence of an MTL derived from N-(dialkylaminoalkylenyl)benzamide residue.European journal of medicinal chemistry 07/2011; 46(11):5705-10. · 3.27 Impact Factor
