AAZTA: An Ideal Chelating Agent for the Development of ⁴⁴Sc PET Imaging Agents

Abstract

Unprecedented fast and efficient complexation of ScIII was demonstrated with the chelating agent AAZTA (AAZTA=1,4‐bis(carboxymethyl)‐6‐[bis(carboxymethyl)]amino‐6‐methylperhydro‐1,4‐diazepine) under mild experimental conditions. The robustness of the 44Sc(AAZTA)− chelate and conjugated biomolecules thereof is further shown by in vivo PET imaging in healthy and tumor mice models. The new results pave the way towards development of efficient Sc‐based radiopharmaceuticals using the AAZTA chelator.

Synthesis, Physicochemical, Labeling and In Vivo Characterization of 44Sc-Labeled DO3AM-NI as a Hypoxia-Sensitive PET Probe

“…The first step in the physicochemical studies of the Sc(III) chelate was to assess the rate of complex formation at an acidic pH, since based on equilibrium data published in the literature for Sc(III) complexes of DOTA, DTPA or AAZTA ligands one can expect that the formation of the (likely quite stable) Sc(DO3AM-NI) complex is expected at a low pH [19,20]. 1 H and 45 Sc NMR measurements performed at pH = 1.52 show that the complex formation reaches equilibrium in about twelve hours (Figures S1-S3).…”

PIDAZTA: Structurally Constrained Chelators for the Efficient Formation of Stable Gallium‐68 Complexes at Physiological pH

“…In this context, the chelator AAZTA (Figure ) was recently shown to be a highly interesting scaffold, because it quickly forms thermodynamically stable complexes with gallium(III) and other ions of diagnostic interest . Bifunctional derivatives of AAZTA were used in conjugates with peptides (Tyr 3 ‐Octreotide and Minigastrin) and RGD‐peptidomimetics showing accumulation in tumors of the corresponding 68 Ga III chelates, and with the bisphosphonate group for PET imaging of bones .…”

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

“…The established diagnostic power of the Positron Emission Tomography (PET) technique in MI and the increasing availability of new biological targeting vectors have led to the design and testing of a large number of radiopharmaceuticals in oncology, cardiology, neurology, and infectious diseases. [1] The introduction of radionuclides like 3 H, 11 C or 18 F to biological targeting vectors needs time consuming synthesis. Taking the half-life of these nuclides into account, this is the main disadvantage for these radioisotopes in means of preparation and examination of their derivatives.…”

“…[15] Its coordination properties towards a wide array of metal ions have been reported, showing its remarkable affinities to lanthanides and transition metal ions. [16][17][18][19] The ready availability of AAZTA and recent descriptions of its lipophilic derivatives for targeting high density lipoproteins (HDL), [20] cell FULL PAPER membranes, [21] the synthesis of bifunctional compounds for conjugation purposes, [22] and the fast formation of complexes prompted us to explore the possibility of employing the AAZTA platform for developing useful complexes for targeted PET applications. [23] Based on the 6-amino-1,4-diazapine (DATA) scaffold new hexadentate chelators were developed by Waldron et al that shows favourable complexation behaviour.…”