• Aucun résultat trouvé

en fr

N/A
N/A
Protected

Academic year: 2021

Partager "en fr "

Copied!
2
0
0

Texte intégral

(1)

HAL Id: hal-03154642

https://hal.archives-ouvertes.fr/hal-03154642

Submitted on 10 Mar 2021

HAL is a multi-disciplinary open access

archive for the deposit and dissemination of

sci-entific research documents, whether they are

pub-lished or not. The documents may come from

teaching and research institutions in France or

abroad, or from public or private research centers.

L’archive ouverte pluridisciplinaire HAL, est

destinée au dépôt et à la diffusion de documents

scientifiques de niveau recherche, publiés ou non,

émanant des établissements d’enseignement et de

recherche français ou étrangers, des laboratoires

publics ou privés.

Radiolabeling by aluminum fluoride-18 complexation:

method optimization on a NODA-based model for

application to sensitive biomolecule as PET tracers for

oncology

Carine San, Nicolas Vignal, Benoit Hosten, Marc Port, Laure Sarda-Mantel,

Fabienne Dioury

To cite this version:

Carine San, Nicolas Vignal, Benoit Hosten, Marc Port, Laure Sarda-Mantel, et al.. Radiolabeling by

aluminum fluoride-18 complexation: method optimization on a NODA-based model for application

to sensitive biomolecule as PET tracers for oncology. Société de chimie Thérapeutique, 28th Young

Research Fellows Meeting /Journées Jeunes Chercheurs, Feb 2021, Paris (en ligne), France.

�hal-03154642�

(2)

On Kinetex C18 column:

-Radio detection: good separation between uncomplexed {Al18F} + 18F -and radiolabelled Al18F-L 👍

-UV detection: no separation of the different AlX-L species 👎

👉Change for Kinetex Evo C18 (Fig 1.)

Radiolabeling by aluminum fluoride-18 complexation: method

optimization on a NODA-based model for application to sensitive

biomolecule as PET tracers for oncology

Carine SAN(1,2)*, Nicolas VIGNAL(2,3), Benoît HOSTEN(2,4), Marc PORT(1), Laure SARDA-MANTEL(2,3), Fabienne DIOURY(1)*.

(1) Conservatoire national des Arts et métiers, HESAM Université, Laboratoire GBCM, EA 7528, 2 rue Conté, 75003 Paris (2) Université de Paris, Institut de Recherche Saint-Louis, Unité Claude Kellershohn, 1 avenue Claude Vellefaux, 75010 Paris (3) AP-HP, Hôpital Lariboisière, Médecine Nucléaire, 2 rue Ambroise-Paré, 75010 Paris

(4) AP-HP, Hôpital Saint-Louis, Pharmacie, 1 avenue Claude Vellefaux, 75010 Paris

Fluorine-18 (18F) is the most favorable positon emitter for tumor imaging. However, direct18F-labeling of biomolecules is challenging as

it involves multiple steps and stringent conditions that are generally not suitable for biomolecules whose integrity may be altered. Over

the past decade, an elegant new approach has been developed by coordination of aluminum fluoride {Al-18F}.(a)

The objective of this work was to implement such a method and to find the mildest conditions compatible with heat- or acid-sensitive

biomolecules. To evaluate {Al-18F} complexation, NODA-MP-C4, a derivative of the commercially available NODA-MP-NCS, was prepared

as a model compound. This model bears a thiourea function to mimic that present in the final conjugates. To guide the operational conditions in radiochemistry, a complementary study in cold series was performed.

Introduction

Introduction

Materials and methods

Materials and methods

18F activity (MBq) 18F volume (µL) Reaction volume (µL) Reactor type* 1 or 2 pot(s)† Radiofluoration yield (%) 1 250 50 110 Tube 2 32 % 2 250 50 110 Tube 1 48 % 3 500 50 110 Tube 2 22 % 4 500 50 110 Tube 1 24 %

Fluorine-18 transport tubing replacement

5 250 50 110 Tube 2 87 % 6 250 50 110 Tube 1 81 % 7 500 50 110 Tube 2 83 % 8 500 50 110 Tube 1 82 % 9 500 50 110 Vial 1 75 % 10 500 25 85 Vial 1 71 % 11 500 25 85 Vial 1 74 % 12 250 12.5 72.5 Vial 1 76 % 13 250 12.5 72.5 Vial 1 79 %

Results and discussion

Results and discussion

* Correspondence: carine.san@aphp.fr;fabienne.dioury@lecnam.net

Conclusion

Conclusion

Acknowledgements:

With financial support: ITMO Cancer of Aviesan on funds administered by Inserm, and Comité Paris de la Ligue Nationale contre le Cancer

XXVIIIthYoung Research Fellow Meeting – 11-12thFebruary 2021

Fig 2.: Representative radio-HPLC chromatograms of the radiolabeling reaction mixture (a: UV 254 nm, b: radio)

Column: Kinetex C18 50 x 2.1 mm 2.6 µm, mobile phase: H2O/MeCN,

gradient: 95/5 to 5/95, flow rate: 0.7 mL/min, injection volume: 5 µL Table: Radiofluoration yield according to 18F concentration,

reactor type and number of pots

1. Production and purification of 18F 2. Radiolabeling of H2L 3. Radiofluoration yield determination by radio-HPLC Radiochemistry 1. Synthesis of references 2. Identification of references by LC-MS

3. Optimization of the analytic LC method

“Cold” chemistry

*tube = test tube = open reactor ; vial = for HPLC sample = sealed reactor †one-pot = mixture of H2L , AlCl3and 18F ; two-pot = premixture of AlCl3and 18F added on H2L

Bibliographic references:

(a)McBride, W. J. et al. J. Nucl. Med. 2009, 50 (6), 991–998. (b) Huynh, P. T. et al. New J. Chem. 2019, 43 (38), 15389–15395. (c)Shetty, D. et al. Bioorg. Med. Chem. 2012, 20 (19), 5941–5947.

H2L AlX-L

X = 19F, OH, OAc

1 AlCl3+ 0.5 NaF

[AlFi(3-i)+ ]

Buffer AcO-H/Na pH4.5 r.t. > 5 min

Buffer AcO-H/Na pH4.5, EtOH (10%), 15 min, reflux

Fig 1.: Representative chromatogram of references Column: Kinetex Evo C18 100 x 4.6mm 5 µm, mobile phase: acetate buffer pH4.5/MeCN 85/15 isocratic, flow rate: 1 mL/min, injection volume: 25 µL, UV detection: 254 nm NODA-MP-C4 (H2L) AlX-NODA-MP-C4 (AlX-L)

X = 18F/19F, OH, OAc

Buffer AcO-H/Na pH4.0, 25 min, reflux 1,3.10-4 18F (250-500 MBq) + 1 AlCl3 NODA-MP-NCS (from Chematech) 1) NaOH aq 2) nBu-NH2 H2O, 1.5h, 50°C

a

b

Al18F-NODA-MP-C4 was obtained with a reproducible satisfactory radiofluoration

yield (79 % ± 8 % (n=9)) on comparison with reported results on NODA-derivatives (60 % to 90 %).(b,c)

-Reactor wall thickness influences the inertia to reach the reflux and the real time of warming.

-Transport tubing replacement highlights the impact of fluorine-18 molar activity (ratio 18F/19F) on radiofluoration yield

Figure

Fig 2.: Representative radio-HPLC chromatograms of the radiolabeling reaction mixture (a: UV 254 nm, b: radio)

Références

Documents relatifs

Les composes de l'invention peuvent etre utilises pour preparer les nano particules soit sous forme d'un compose unique de formule (I) , soit sous forme d'un melange de composes

The authors conclude that learning effects seem to be at work and that the startup size has an important effect on the subsequent growth of firms.. Explain why we can say that based

Un fichier objet (extension .o sous Linux, .obj sous Windows) contient les instructions en langage machine correspondant au source et des données destinées à l’éditeur de lien afin

Ce matériel pédagogique, dont les fonctions sont très proches du système de Camescasse, fut inventé par un instituteur belge, Georges Cuisenaire (Quaregnon, 1891 -  Thuin, 1975),

Cliej de la section des essais de machines au Laboratoue d'Essais du Conservaient e National des Ai ts et Métieis. 0) Les parties conduisant le courant seront protégées contie

— Sont abrogées toutes les dispositions de loi ou de règlement contraires à la présente loi... Disposition générale de

Si, dans les portées courantes de 40 à 50 mètres, on peut admettre pour les deux métaux des poteaux de m ê m e hauteur, la variation totale de la flèche étant relativement

ïïff 3.. Court-circuit provenant du contact de branches d'arbres, de chutes d'arbres, de chutes de pierres, du contact d'ani- maux, ou du contact direct des fils entre eux.