⁶⁸Ga‐Ca‐phytate particles: A potential lung perfusion agent of synthetic origin prepared in a cold kit format

Abstract

The objective of this study was to investigate the radiosynthesis of Ga-Ca-phytate particles and then characterize the formulation for radiochemical purity, radioactive particle size distribution, and biodistribution in normal rats. This radiotracer was prepared using a commercial phytate cold kit after reconstitution with saline, Ga-chloride generator eluent, calcium chloride, and air, then heating at 100°C for 30 minutes to achieve 99% radiochemical purity of Ga-particles that were 21% 3-5 μm, 8% 5-15 μm, and 71%>15 μm in diameter. This optimal formulation was stable for 2 hours at room temperature. Intravenous administration of Ga-particles in rats resulted in an uptake of 93% in the lungs, 4% in the liver plus spleen, and 3% in the carcass after 20 minutes. Two-thirds of the carcass activity was radioactive blood, likely to be Ga-transferrin. The positron emission tomography image was superior than the Tc-MAA image because it displayed high lung uptake against a low background. Low uptake by the liver, spleen did not interfere with the diagnostic quality, and faint activity in the submandibular (salivary) glands was due to Ga-transferrin. The preclinical data so far indicate that Ga-Ca-phytate particles have good potential as a lung perfusion imaging agent.

Preparation of 68Ga‐Mg‐Ca‐phytate colloid and its evaluation as a liver imaging agent

“…Excessive large 68 Ga‐particles from reaction 21 suggested it was necessary to reduce the larger population, perhaps by slowing down particle formation. The acceptable range of 0.02‐0.2 μm 68 Ga‐particles obtained in reactions 22, 25 and 7 allowed for some accretion in vivo, but not above ~5 μm that would be expected to result in lung uptake …”

“…So for “ new particle growth ,” the mechanism involved ionic calcium coordinating intermolecularly between 68 Ga‐phytate units as described above and elsewhere. Other factors such as complement proteins, antibodies and immune cells could have also contributed to particle growth, and ultimately the radioactive immune‐complexes concentrated in the liver. The very low lung uptake indicated 68 Ga‐particles were less than ~5 μm, with or without immune‐cell binding.…”

“…There are many reported examples of this chemistry, one more recent and relevant study showed 68 Ga 3+ mixed with stannous-phytate and Ca 2+ in aqueous acid at 100°C for 30 minutes yielded 71% of >15 μm 68 Ga-particles. 15 This methodology was advanced further here, to prepare smaller 68 Ga-particles with a similar matrix comprising of inositol hexaphosphate subunits.…”

“…The acceptable range of 0.02-0.2 μm 68 Ga-particles obtained in reactions 22, 25 and 7 allowed for some accretion in vivo, but not above~5 μm that would be expected to result in lung uptake. 15 CMC has been used in many pharmaceutical formulations as a thickener, stabiliser and suspending agent. In the 68 Ga-phytate preparations here, it substantially enhanced the smaller population at the expense of coarse particles in reactions 23 and 24 (cf: rxn 21).…”

“…This radiopharmacy has previously explored the aqueous chemistry of radiogallium, including the preparation of radioactive particles with matrices of hydrolysed stannous fluoride, or PA using simplified cold kit methodology . The aim of this project was to advance the knowledge of the aqueous chemistry of 68 Ga(III) by preparing a 68 Ga‐mixed metal‐phytate colloid that could be suitable for liver imaging.…”