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Background  6-[Bis(carboxymethyl)amino]-1,4-bis(carboxymethyl)-6-methyl-1,4-diazepane (AAZTA ) is a promising chelator with potential advantages over 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for radiopharmaceutical applications. Its mesocyclic structure enables fast radiolabelling under mild conditions with trivalent metals including not only  68 Ga for positron emission tomography (PET) but also  177 Lu and  111 In for single-photon emission computed tomography (SPECT) and radionuclide therapy. Here, we describe the evaluation of a bifunctional AAZTA derivative conjugated to a model minigastrin derivative as a potential theranostic agent.    Methods  An AAZTA derivative with an aliphatic C 9  chain as linker was coupled to a minigastrin, namely [AAZTA 0 , D-Glu 1 , desGlu 2–6 ]-minigastrin (AAZTA-MG), and labelled with  68 Ga,  177 Lu and  111 In. The characterisation in vitro included stability studies in different media and determination of logD (octanol/PBS). Affinity determination (IC 50 ) and cell uptake studies were performed in A431-CCK2R cells expressing the human CCK2 receptor. μPET/CT and ex vivo biodistribution studies were performed in CCK2 tumour xenograft-bearing nude mice and normal mice.    Results  AAZTA-MG showed high radiochemical yields for  68 Ga (>95 %),  177 Lu (>98 %) and  111 In (>98 %). The logD value of −3.7 for both [ 68 Ga]- and [ 177 Lu]-AAZTA-MG indicates a highly hydrophilic character. Stability tests showed overall high stability in solution with some degradation in human plasma for [ 68 Ga]- and transchelation towards DTPA for and [ 177 Lu]-AAZTA-MG. An IC 50  value of 10.0 nM was determined, which indicates a high affinity for the CCK2 receptor. Specific cell uptake after 60 min was >7.5 % for [ 68 Ga]-AAZTA-MG and >9.5 % for [ 177 Lu]-AAZTA-MG, comparable to other DOTA-MG-analogues. μPET/CT studies in CCK2 receptor tumour xenografted mice not only revealed high selective accumulation in A431-CCK2R positive tumours of  68 Ga-labelled AAZTA-MG (1.5 % ID/g in 1 h post injection) but also higher blood levels as corresponding DOTA-analogues. The  111 In-labelled peptide had a tumour uptake of 1.7 % ID/g. Biodistribution in normal mice with the [ 177 Lu]-AAZTA-MG showed a considerable uptake in intestine (7.3 % ID/g) and liver (1.5 % ID/g).    Conclusion  Overall, AAZTA showed interesting properties as bifunctional chelator for peptides providing mild radiolabelling conditions for both  68 Ga and trivalent metals having advantages over the currently used chelator DOTA. Studies are ongoing to further investigate in vivo targeting properties and stability issues and the influence of spacer length on biodistribution of AAZTA.    Electronic supplementary material  The online version of this article (doi:10.1186/s13550-015-0154-7) contains supplementary material, which is available to authorized users.

Influence of a novel, versatile bifunctional chelator on theranostic properties of a minigastrin analogue