Synthesis, radiolabeling and preliminary in vivo evaluation of multimodal radiotracers for PET imaging and targeted radionuclide therapy of pigmented melanoma.

Melanin pigment represents an attractive target to address specific treatment to melanoma cells, such as cytotoxic radionuclides. However, less than half of the patients have pigmented metastases. Hence, specific marker is required to stratify this patient population before proceeding with melanin-targeted radionuclide therapy.

Synthesis, radiofluorination, and in vivo evaluation of novel fluorinated and iodinated radiotracers for PET imaging and targeted radionuclide therapy of melanoma.

Our project deals with a multimodal approach using a single fluorinated and iodinated melanin-targeting structure and offering both imaging (positron emission tomography (PET)/fluorine-18) and treatment (targeted radionuclide therapy/iodine-131) of melanoma. Six 6-iodoquinoxaline-2-carboxamide derivatives with various side chains bearing fluorine were synthesized and radiofluorinated, and their in vivo biodistribution was studied by PET imaging in B16Bl6 primary melanoma-bearing mice. Among this series, [(18)F]8 emerged as the most promising compound.

Synthesis, radioiodination and in vivo screening of novel potent iodinated and fluorinated radiotracers as melanoma imaging and therapeutic probes.

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.

In vivo scintigraphic imaging of proteoglycans.

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.

New aldehyde and vinylsulfone proteasome inhibitors for targeted melanoma therapy.

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).