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Article Dans Une Revue Journal of Chromatography A Année : 2018

Coupling a gamma-ray detector with asymmetrical flow field flow fractionation (AF4): Application to a drug-delivery system for alpha-therapy

Résumé

Alpha-particle-emitting radionuclides have been the subject of considerable investigation as cancer ther-apeutics, sincethey have the advantages of highpotency and specificity. Among ␣-emitting radionuclides that are medically relevant and currently available, the lead-212/bismuth-212 radionuclide pair could constitute an in vivo generator. Considering its short half-life (T 1/2 = 60.6min), 212 Bi can only be delivered using labelled carrier molecules that would rapidly accumulate in the target tumor. To expand the range of applications, an interesting method is to use its longer half-life parent 212 Pb (T 1/2 = 10.6 h) that decays to 212 Bi. The challenge consists in keeping 212 Bi bound to the vector after the 212 Pb decay. Preclinical and clinical studies have shown that a variety of vectors may be used to target alpha-emitting radionu-clidesto cancer cells. Nanoparticles, notably liposomes,allow combinedtargeting options, achieving high specific activities, easier combination of imaging and therapy and development of multimodality therapeutic agents (e.g., radionuclide therapy plus chemotherapy). The aim of thiswork consists in assessing the in vitro stabilityof 212 Pb/ 212 Bi encapsulation in the liposomes. Indeed, the release of the radionuclide from the carrier molecules might causes toxicity to normal tissues. To reach this goal,Asymmetrical Flow Field-Flow Fractionation(AF4) coupled with a Multi-Angle Light Scattering detector (MALS) was used and coupling with a gamma () ␥ ray detector was developed. AF4-MALS-␥ was shown to be a powerful tool for monitoring the liposome size together with the incorporation of the high energy alpha emitter. This was successfully extended to assess thestability of 212 Bi-radiolabelled liposomes in serum showing that more than 85% of 212 Pb/ 212 Bi is retained after 24 h of incubation at 37 • C.
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Dates et versions

inserm-01900710 , version 1 (22-10-2018)

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Sandrine Huclier-Markai, Alicia Grivaud-Le Du, Estelle N’tsiba, Gilles F Montavon, Marie Mougin-Degraef, et al.. Coupling a gamma-ray detector with asymmetrical flow field flow fractionation (AF4): Application to a drug-delivery system for alpha-therapy. Journal of Chromatography A, 2018, 1573, pp.107 - 114. ⟨10.1016/j.chroma.2018.08.065⟩. ⟨inserm-01900710⟩
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