Development of radiotracers for targeted radionuclide therapy of melanoma

Updated: 3 months ago
Location: Clermont Ferrand, AUVERGNE
Job Type: FullTime
Deadline: 29 Jun 2024

22 Feb 2024
Job Information
Organisation/Company

UMR 1240 INSERM UCA (IMoST)
Research Field

Chemistry
Biological sciences » Biology
Medical sciences
Researcher Profile

Recognised Researcher (R2)
Leading Researcher (R4)
First Stage Researcher (R1)
Established Researcher (R3)
Country

France
Application Deadline

29 Jun 2024 - 22:00 (UTC)
Type of Contract

Temporary
Job Status

Full-time
Offer Starting Date

1 Sep 2024
Is the job funded through the EU Research Framework Programme?

Not funded by an EU programme
Is the Job related to staff position within a Research Infrastructure?

No

Offer Description

Despite recent advances in immunotherapy treatments, metastatic melanoma remains associated with poor prognosis. We previously reported the development of a small molecule, called ICF01012 and targeting melanin pigments, that has been radiolabelled with iodine-131 and evaluated for targeted radionuclide therapy (TRT) of pigmented melanoma in several preclinical models. The significant antitumour effects observed with this [131 I]ICF01012 treatment prompted us to start an ongoing phase I clinical study (NCT03784625). However, the regulatory constraints for the radiosynthesis and handling of such iodine radionuclides and associated radiotracers as well as the clinical management of patients receiving high dose of [131 I]ICF01012 encourage us to further investigate a second generation of melanin-targeted ligands radiolabelled with less restrictive metallic radionuclides for TRT (e.g. copper-67, lutetium-177 and et terbium-161 (beta- -emitters) or actinium-225 (alpha-emitter)). The recruited PhD student will be in charge of the synthesis and characterization of ICF01012 analogues conjugated with polyazamacrocycles for metal radionuclide chelation. He/she will optimize the radiolabelling procedures and will participate to the preclinical evaluation of the radiotracers including stability and selectivity studies, cellular uptake, biodistribution and antitumour efficacy experiments in relevant mice models. This research project, part of the SIRIC LYriCAN+ program, will take benefit from the complementary and multidisciplinary expertise in radiopharmaceutical development of the IMoST (Clermont-Fd) and LAGEPP (Lyon) laboratories.

 

References: [1] Thivat E, Rouanet J, Auzeloux P, Sas N, Jouberton E, Levesque S, Billoux T, Mansard S, Molnar I, Chanchou M, Fois G, Maigne L, Chezal JM, Miot-Noirault E, D'Incan M, Durando X, Cachin F. Phase I study of [131 I]ICF01012, a targeted radionuclide therapy, in metastatic melanoma: MELRIV-1 protocol. BMC Cancer 2022, 22(1):417. doi: 10.1186/s12885-022-09495-3.

 

[2] Parat A, Kryza D, Degoul F, Taleb J, Viallard C, Janier M, Garofalo A, Bonazza P, Heinric-Balard L, Cohen R, Miot-Noirault E, Chezal JM, Billotey C, Felder-Flesch D. Radiolabeled dendritic probes as tools for high in vivo tumor targeting: application to melanoma. J Mater Chem B 2015 3(12):2560-71. doi: 10.1039/c5tb00235d.

 

[3] Maisonial A, Kuhnast B, Papon J, Boisgard R, Bayle M, Vidal A, Auzeloux P, Rbah L, Bonnet-Duquennoy M, Miot-Noirault E, Galmier MJ, Borel M, Askienazy S, Dollé F, Tavitian B, Madelmont JC, Moins N, Chezal JM. Single photon emission computed tomography/positron emission tomography imaging and targeted radionuclide therapy of melanoma: new multimodal fluorinated and iodinated radiotracers. J Med Chem 2011, 54(8):2745-66. doi: 10.1021/jm101574q.

 

[4] Chezal JM, Papon J, Labarre P, Lartigue C, Galmier MJ, Decombat C, Chavignon O, Maublant J, Teulade JC, Madelmont JC, Moins N. Evaluation of radiolabeled (hetero)aromatic analogues of N-(2-diethylaminoethyl)-4-iodobenzamide for imaging and targeted radionuclide therapy of melanoma. J Med Chem 2008, 51(11):3133-44. doi: 10.1021/jm701424g.

Funding category: Contrat doctoral
French National Cancer institute (INCA), SIRIC LYriCAN+ program
PHD title: Doctorat de chimie
PHD Country: France


Requirements
Specific Requirements

We are looking for a highly motivated candidate having the desire to work on a multidisciplinary research topic at the interface of organic chemistry/radiochemistry and biology. The candidate must have a master degree (or equivalent) in chemistry. A solid knowledge in organic chemistry (experimental and theorical) and in classical purification and analysis procedures (HPLC, flash chromatography, NMR, mass spectroscopy, …) is mandatory. Experience in radiochemistry will also be an asset. A good level (written/spoken) of English will be essential. In addition, a mobility between Clermont-Fd and Lyon research sites is asked.

 


Additional Information
Work Location(s)
Number of offers available
1
Company/Institute
UMR 1240 INSERM UCA (IMoST)
Country
France
City
Clermont-Ferrand
Geofield


Where to apply
Website

https://www.abg.asso.fr/fr/candidatOffres/show/id_offre/120556

Contact
Website

https://imost.uca.fr/

STATUS: EXPIRED