Arsenic-72 (72As) and 77As have nuclear properties suitable for use in radiopharmaceuticals. 72As is a positron emitter making it useful in positron emission tomography (PET) imaging. 77As is a beta emitter whose emissions have appropriate energy to treat cancer. This makes the two isotopes a perfect pair for diagnosis and targeted radiotherapy, since they are the same element. 77As is produced by neutron irradiation of 76Ge to form 77Ge, which decays to 77As. The 77As is separated from a neutron irradiated 76GeO2 target using silica gel column chromatography to yield no carrier added 77As. The 77As is eluted in oxidation state +5 as [77As]arsenate. Trithiol ligands have been shown to form stable 77As(III) complexes in high radiochemical yield. For translation to use in targeted radiotherapy, a bombesin peptide was incorporated into a trithiol ligand as a bifunctional chelate. Bombesin (BBN) is a peptide with high affinity for the gastrin releasing peptide receptor, which is highly expressed on several cancers including prostate, small cell lung and breast cancers. A trithiocyanate protected trithiol ligand was conjugated to the bombesin (BBN) peptide following standard procedures used in peptide synthesis. This Trithiol-BBN precursor was deprotected with tris(2-carboxyethyl)phosphine (TCEP) to generate the Trithiol-BBN ligand. Radiolabeling of the Trithiol-BBN ligand required reduction of 77As(V) to 77As(III); ammonium mercaptoacetate (NH4SR) was used as the reducing agent to yield 77As(SR)3, which was then reacted with the Trithiol-BBN to yield the desired 77As-Trithiol-BBN complex in greater than 95% yield. Verification of complex formation was done by comparison with the non-radioactive standard 75As-Trithiol-BBN using reversed-phase HPLC. The non-radioactive standard had been characterized by LC-MS. The stability of the 77As-Trithiol-BBN was investigated following purification. The addition of ascorbic acid was necessary to minimize radiolysis.

Radiolabeling of a trithiol-bombesin ligand with 77As and 72as for use as radiopharmaceuticals

253rd National Meeting (2017)

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