⁶⁸Ga‐PET: a powerful generator‐based alternative to cyclotron‐based PET radiopharmaceuticals

Abstract

PET (positron emission tomography) is a powerful diagnostic and imaging technique which requires short-lived positron emitting isotopes. The most commonly used are accelerator-produced (11)C and (18)F. An alternative is the use of metallic positron emitters. Among them (68)Ga deserves special attention because of its availability from long-lived (68)Ge/(68)Ga generator systems which render (68)Ga radiopharmacy independent of an onsite cyclotron. The coordination chemistry of Ga(3+) is dominated by its hard acid character. A variety of mono- and bifunctional chelators have been developed which allow the formation of stable (68)Ga(3+)complexes and convenient coupling to biomolecules. (68)Ga coupling to small biomolecules is potentially an alternative to (18)F- and (11)C-based radiopharmacy. In particular, peptides targeting G-protein coupled receptors overexpressed on human tumour cells have shown preclinically and clinically high and specific tumour uptake. Kit-formulated precursors along with the generator may be provided, similar to the (99)Mo/(99m)Tc-based radiopharmacy, still the mainstay of nuclear medicine.

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

“…These probes can be used for diagnosis via PET or SPECT imaging. [2] The major concern for most radionuclides is their availability and their means of production. Therefore, the use of generator produced isotopes has become of great interest over the last few years.…”

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

“…It was reported that certain fragments of UBI, including the 29-41 fragment exhibit features that make them good candidates for targeting vectors in the development of tracers for PET [5,7]. Although most research into the development of radioactive tracers for detection and imaging of infection, including studies investigating UBI fragments, has been performed using 99m Tc as a radionuclide [8], a variety of other radionuclides are available for use in tracers; problems associated with some radionuclides are poor image quality, excessive radiation dose to the patient, undesirably long or short radioactive half-life, or the requirement of an in-house cyclotron [4,9]. Although 99m procedures today, a growing number of diagnostic radiotracers are based on molecules labeled with PET radionuclides such as 18 F, 11 C and more recently 68 Ga and 64 Cu.…”

“…The relatively straight-forward radiolabeling of most bi-functional chelators makes these kinds of tracers suitable for mass production in kit form that can be distributed to, and used by staff at hospitals and clinics where an on-site radionuclide generator is present [9,10].…”

“…However, more recently, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) has been investigated as a potential bifunctional chelator for use in tracers, as, unlike DOTA, efficient radiolabeling of NOTA tracers can occur without heating to temperatures which risk damaging targeting vectors such as peptides [9][10][11]. Due to the smaller dimensions of the macrocyclic cavity of NOTA, as compared to DOTA, the stability of a NOTA chelate containing a small cation such as 68 Ga is greater [10].…”

“…Due to the smaller dimensions of the macrocyclic cavity of NOTA, as compared to DOTA, the stability of a NOTA chelate containing a small cation such as 68 Ga is greater [10]. This leads to greater thermodynamic and kinetic stability [12,13], which is advantageous as it makes the NOTA-peptide conjugate both easier to label and more resistant to trans-metallation in the body [9,13]. If, as in most reported cases (for instance DOTATATE), the NOTA or DOTA chelator is linked to the peptide via one of the acid groups (as is also reported herein) the conjugation ability of the chelator is reduced as compared to linking to the peptide via the carbon backbone.…”