= 1.6 kBq/nmol) experiment, respectively. At 2 h post-injection, tumour-to-blood ratios of 20.4 ± 3.4 and 4.8 ± 2.4 were obtained for the non-blocking (molar activity > 200 kBq/nmol) and blocking (M.A. Moreover, a melanocortin 1 receptor-targeting peptide conjugate, DOTA-modified cyclized α-melanocyte-stimulating hormone (DOTA-CycMSH), was radiolabeled with 225Ac and proof-of-principle biodistribution studies using B16F10 tumour-bearing mice were conducted.
Of the many polydentate picolinic acid (“pa”) containing ligands evaluated (H 4octapa, H 4 CHXoctapa, p-NO 2-Bn-H 4neunpa, and H 6phospa ), all out-performed the current gold standard, DOTA for 225Ac radiolabeling ability at ambient temperature.
MBq quantities of 225Ac and parent radium-225 ( 225Ra, t 1/2 = 14.8 d) were produced and separated using solid phase extraction DGA resin, resulting in a radiochemically pure 225Ac product in > 98% yield and in an amenable form for radiolabeling of ligands and bioconjugates. We at TRIUMF have leveraged our Isotope Separation On-Line (ISOL) facility to produce 225Ac and use the resulting radioactivity to screen a number of potential 225Ac-radiopharmaceutical compounds.
Actinium-225 ( 225Ac, t 1/2 = 9.9 d) is a promising candidate radionuclide for use in targeted alpha therapy (TAT), though the currently limited global supply has hindered the development of a suitable Ac-chelating ligand and 225Ac-radiopharmaceuticals towards the clinic.