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. 2017;1(1):4.
doi: 10.1186/s41181-016-0007-3. Epub 2016 Mar 21.

DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature

Johanna Seemann  1 , Bradley Waldron  1 , David Parker  2 , Frank Roesch  1
Affiliations

DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature

Johanna Seemann et al. EJNMMI Radiopharm Chem. 2017.

Erratum in

Abstract

Background: The widespread acceptance and application of 68Ga-PET depends on our ability to develop radiopharmaceuticals that can be prepared in a convenient and suitable manner. A kit-type labelling protocol provides such characteristics and requires chelators that can be radiolabelled under exceptionally mild conditions. Recently the DATA chelators have been introduced that fulfil these requirements. In continuing their development, the synthesis and radiolabelling of the first DATA bifunctional chelator (BFC) and peptide conjugate are described.

Results: A BFC derived from the DATA ligand (2,2'-(6-((carboxymethyl)amino)-1,4-diazepane-1,4-diyl)diacetic acid) has been synthesised in five steps from simple building blocks, with an overall yield of 8 %. DATAM5-3tBu (5-[1,4-Bis-tert-butoxycarbonylmethyl-6-(tert-butoxycarbonylmethyl-methyl-amino)-[1, 4]diazepan-6-yl]-pentanoic acid) has been coupled to [DPhe1][Tyr3]-octreotide (TOC) and the resulting peptide conjugate (DATATOC) radiolabelled with purified 68Ga derived via four different 68Ge/68Ga generator post-processing (PP) methods. The stability and lipophilicity of the radiotracer have been assessed and a kit-type formulation for radiolabelling evaluated. 68Ga-DATATOC has been prepared with a > 95 % radiochemical yield (RCY) within 1 (fractionated and acetone-PP) and 10 min (ethanol- and NaCl-PP) at 23 °C (pH 4.2-4.9, 13 nmol). The radiolabelled peptide is stable in the presence of human serum. Lipophilicity of 68Ga-DATATOC was calculated as logP = -3.2 ± 0.3, with a HPLC retention time (tR = 10.4 min) similar to 68Ga-DOTATOC (logP = -2.9 ± 0.4, tR = 10.3 min). Kit-type labelling from a lyophilised solid using acetone-PP based labelling achieves > 95 % RCY in 10 min at 23 °C.

Conclusions: The favourable labelling properties of the DATA chelators have been retained for DATATOC. High radiochemical purity can be achieved at 23 °C in less than 1 min and from a kit formulation. The speed, reliability, ease, flexibility and simplicity with which 68Ga-DATATOC can be prepared makes it a very attractive alternative to current standards.

Keywords: 68Ga; DATA; Kit-type labelling; TOC.

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Figures

Fig. 1
Fig. 1
DATAM, bifunctional prochelator DATAM5-3tBu and DATATOC (left to right)
Fig. 2
Fig. 2
Synthesis of the unconjugated DATA prochelator - DATAM5-3tBu. (i) Amberlyst-21, EtOH; (ii) CH2O, EtOH; (iii) CH3COOH, Pd(OH)2/C, H2, EtOH; (iv) BrCH2COOtBu, K2CO3, MeCN; (v) CH3I, K2CO3, DCM : MeCN; (vi) LiOH, THF : H2O
Fig. 3
Fig. 3
Synthesis of DATATOC
Fig. 4
Fig. 4
Time dependent labelling for the formation of 68Ga-DATATOC using 68Ga post-processed by fractionation, acetone-, ethanol- and NaCl-based procedures
See this image and copyright information in PMC

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