English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Purpose  The widespread use of  68 Ga for positron emission tomography (PET) relies on the development of radiopharmaceutical precursors that can be radiolabelled and dispensed in a simple, quick, and convenient manner. The DATA (6-amino-1,4-diazapine-triacetate) scaffold represents a novel hybrid chelator architecture possessing both cyclic and acyclic character that may allow for facile access to  68 Ga-labelled tracers in the clinic. We report the first bifunctional DATA chelator conjugated to [Tyr 3 ]octreotide (TOC), a somatostatin subtype 2 receptor (SST 2 )-targeting vector for imaging and functional characterisation of SSTR 2  expressing tumours.    Methods  The radiopharmaceutical precursor, DATA-TOC, was synthesised as previously described and used to complex  nat Ga(III) and  68 Ga(III). Competition binding assays of [ nat Ga]Ga-DATA-TOC or [ nat Ga]Ga-DOTA-TOC against [ 125 I-Tyr 25 ]LTT-SS28 were conducted in membranes of HEK293 cells transfected to stably express one of the hSST 2,3,5  receptor subtypes (HEK293-hSST 2/3/5  cells). First in vivo studies were performed in female NMRI-nude mice bearing SST 2 -positive mouse phaeochromocytoma mCherry (MPC-mCherry) tumours to compare the in vivo SST 2 -specific tumour-targeting of [ 68 Ga]Ga-DATA-TOC and its overall pharmacokinetics versus the [ 68 Ga]Ga-DOTA-TOC reference. A direct comparison of [ 68 Ga]Ga-DATA-TOC with the well-established PET radiotracer [ 68 Ga]Ga-DOTA-TOC was additionally performed in a 46-year-old male patient with a well-differentiated NET (neuroendocrine tumour), representing the first in human administration of [ 68 Ga]Ga-DATA-TOC.    Results  DATA-TOC was labelled with  68 Ga with a radiolabelling efficiency of > 95% in less than 10 min at ambient temperature. A molar activity up to 35 MBq/nmol was achieved. The hSST 2 -affinities of [ nat Ga]Ga-DATA-TOC and [ nat Ga]Ga-DOTA-TOC were found similar with only sub-nanomolar differences in the respective IC 50  values. In mice, [ 68 Ga]Ga-DATA-TOC was able to visualise the tumour lesions, showing standardised uptake values (SUVs) similar to [ 68 Ga]Ga-DOTA-TOC. Direct comparison of the two PET tracers in a NET patient revealed very similar tumour uptake for the two  68 Ga-radiotracers, but with a higher tumour-to-liver contrast for [ 68 Ga]Ga-DATA-TOC.    Conclusion  [ 68 Ga]Ga-DATA-TOC was prepared, to a quality appropriate for in vivo use, following a highly efficient kit type process. Furthermore, the novel radiopharmaceutical was comparable or better than [ 68 Ga]Ga-DOTA-TOC in all preclinical tests, achieving a higher tumour-to-liver contrast in a NET-patient. The results illustrate the potential of the DATA-chelator to facilitate the access to and preparation of  68 Ga-radiotracers in a routine clinical radiopharmacy setting.    Electronic supplementary material  The online version of this article (10.1186/s13550-019-0516-7) contains supplementary material, which is available to authorized users.

Instant kit preparation of 68Ga-radiopharmaceuticals via the hybrid chelator DATA: clinical translation of [68Ga]Ga-DATA-TOC