Issue 42, 2017

Novel bifunctional DATA chelator for quick access to site-directed PET 68Ga-radiotracers: preclinical proof-of-principle with [Tyr3]octreotide

Abstract

Molecular imaging of tumors with the PET radionuclide 68Ga has gained momentum in clinical oncology due to the expanding availability of commercial 68Ge/68Ga-generators in combination with state-of-the-art PET/CT and PET/MRI hybrid imaging systems. Concurrently, interesting peptide-based or small-size vectors have been developed for theranostic use in cancer patients. Owing to the short half-life of 68Ga (t1/2 = 67.7 min) and the sensitivity of many targeting biomolecules, labeling and kit reconstitution in mild conditions allowing for quick access to ready-for-injection PET-tracers are highly desirable. The novel DATA ((6-pentanoic acid)-6-(amino)methy-1,4-diazepinetriacetate) chelator previously showing promising qualities for kit type labeling, was coupled to TOC ([Tyr3]octreotide). We herein report results from a first proof-of-principle study directly comparing 67Ga-DATA-TOC with the well-established 67Ga-DOTA-TOC in a series of preclinical models. Both analogs were shown to be sst2-preferring and specifically internalized in AR42J and HEK293-hsst2 cells, with 67Ga-DOTA-TOC internalizing faster in both cell lines. Similarly, after injection in mice bearing either AR42J or HEK293-hsst2 tumors, both tracers efficiently and specifically localized in the implants. Whereas 67Ga-DOTA-TOC exhibited higher tumor values, 67Ga-DATA-TOC cleared faster from background tissues. These findings support the suitability of the newly introduced bifunctional chelator DATA as a reliable, quick and convenient means for labeling medically relevant vectors with the PET radiometal 68Ga.

Graphical abstract: Novel bifunctional DATA chelator for quick access to site-directed PET 68Ga-radiotracers: preclinical proof-of-principle with [Tyr3]octreotide

Article information

Article type
Paper
Submitted
09 Mei 2017
Accepted
23 Jun 2017
First published
27 Jun 2017

Dalton Trans., 2017,46, 14584-14590

Novel bifunctional DATA chelator for quick access to site-directed PET 68Ga-radiotracers: preclinical proof-of-principle with [Tyr3]octreotide

B. A. Nock, A. Kaloudi, J. Nagel, J. Sinnes, F. Roesch and T. Maina, Dalton Trans., 2017, 46, 14584 DOI: 10.1039/C7DT01684K

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements