Equilibrium, Kinetic and Structural Properties of Gallium(III) and Some Divalent Metal Complexes Formed with the New DATAm and DATA5m Ligands

The development of 68Ge/68Ga generators has made the positron-emitting 68Ga isotope widely accessible and raised interest in new chelate complexes of Ga3+. The hexadentate 1,4-di(acetate)-6-methyl[amino(methyl)acetate]perhydro-1,4-diazepane (DATAm) ligand and its bifunctional analogue, 1,4-di(acetate)-6-pentanoic acid[amino(methyl)acetate]perhydro-1,4-diazepane (DATA5m), rapidly form complexes with 68Ga in high radiochemical yield. The stability constants of DATAm and DATA5m complexes formed with Ga3+, Zn2+, Cu2+, Mn2+ and Ca2+ have been determined by using pH potentiometry, spectrophotometry (Cu2+) and 1H and 71Ga NMR spectroscopy (Ga3+). The stability constants of Ga(DATAm) and Ga(DATA5m)…

Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer

There is still a great unmet medical need concerning diagnosis and treatment of breast cancer which could be addressed by utilizing specific molecular targets. Tumor-associated MUC1 is expressed on over 90 % of all breast cancer entities and differs strongly from its physiological form on epithelial cells, therefore presenting a unique target for breast cancer diagnosis and antibody-mediated immune therapy. Utilizing an anti-tumor vaccine based on a synthetically prepared glycopeptide, we generated a monoclonal antibody (mAb) GGSK-1/30, selectively recognizing human tumor-associated MUC1. This antibody targets exclusively tumor-associated MUC1 in the absence of any binding to MUC1 on health…

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

Purpose The widespread use of 68Ga 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 68Ga-labelled tracers in the clinic. We report the first bifunctional DATA chelator conjugated to [Tyr3]octreotide (TOC), a somatostatin subtype 2 receptor (SST2)-targeting vector for imaging and functional characterisation of SSTR2 expressing tumours. Methods The radiopharmaceutical precursor, DATA…

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

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 pre…

Synthesis and labeling of a squaric acid containing PSMA-inhibitor coupled to AAZTA5 for versatile labeling with 44Sc, 64Cu, 68Ga and 177Lu

Additional file 1: of Instant kit preparation of 68Ga-radiopharmaceuticals via the hybrid chelator DATA: clinical translation of [68Ga]Ga-DATA-TOC

Table S1. Binding affinities of [natGa]Ga-DATA-TOC and [natGa]Ga-DOTA-TOC on hSST2/3/5, as determined during displacement of [125I-Tyr25]LTT-SS28 from transfected HEK293-hSST2/3/5 cell membranes; LTT-SS28 served as reference. Table S2. Uptake in terms of %IA of [68Ga]Ga-DATA-TOC or [68Ga]Ga-DOTA-TOC in selected organs of MPC-mCherry tumour-bearing female NMRI nu/nu mice 1 h p.i. (218 ± 57 MBq (11.2 nmol peptide/kg) and 441 ± 109 MBq (10.5 nmol peptide)/kg body weight, respectively; blocking after coinjection of 100 µg/mouse [Nal3]octreotide acetate)). Table S3. Radioactivity concentration in terms of SUV of [68Ga]Ga-DATA-TOC or [68Ga]Ga-DOTA-TOC in selected organs of MPC-mCherry tumour-bear…