Physico-chemical characterisation of99mTc-tin fluoride colloid agent used for labelling white cells

Abstract

Tc-tin fluoride colloid is an agent used to label leucocytes, for the imaging and diagnosis of inflammatory conditions including Crohn's disease. Despite previous investigations, this radiolabelling agent is still poorly characterised. The aim of this work was to examine the process of formation and stability of 99m Tc-tin fluoride colloid using mass spectrometry, membrane filtration and atomic absorption spectrophotometric techniques. Tin-oxide bonds in tin clusters were identified in the stannous fluoride reagent vial by mass spectrometry. From radioactive particle size distribution experiments, the facile disruption of radiocolloid particles with excess oxygen gas contrasted to the partial hydrolysis of Sn(II) during the formation process. Under the standard conditions, 10% of particles were determined as 1-3 mm, and this population coordinated 96% of the 99m Tc added. Colloid particle formation and the reduction of 99m Tc-pertechnetate is discussed. Sodium fluoride may optimise 1-3 mm radioactive particle size, by regulating particle growth. Tc-tin fluoride colloid is affected by positive or negative charge, as either Al, Mo ions or solid membranes, resulting in either coagulation and/or deflocculation of the particles.

A study of radiogallium aqueous chemistry:in vitroandin vivocharacterisation of67Ga-hydrolysed-stannous fluoride particles

“…In the absence of NaF and the 0.2 µm filtration step, the pilot reactions afforded large 67 Ga‐ h ‐SnF 2 particles, although these were not characterised above 3 µm. There was no obvious effect when low levels of NaF in 0.06–0.12 mg were present in the reaction mixture, but the radiolabelling efficiency was inhibited above 0.62 mg. As a comparison, it was previously shown that 5 mg NaF in the reaction vial did not inhibit 99m Tc‐ h ‐SnF 2 colloid formation at room temperature . For 67 Ga‐ h ‐SnF 2 particles at 100 °C though, this excipient interfered with 67 Ga‐coordination because 100% of soluble 67 Ga‐ions were detected in the neutralised formulation.…”

“…In this case, it is not clear if acetic acid acts as a neutral donor molecule and/or replaces some fluoride ions during the hydrolysis of Sn 2+ . This result suggested that water is still an important donor molecule, not only to form stannous oxyfluoride, SnO.SnF 2 · 3H 2 O, Sn 2 OF 2 · xH 2 O (x = 0, 3, 4, 6) and 3SnO.2SnF 2 · 6H 2 O, but also to provide oxygen atoms that link with tin atoms in the particle structure.…”

“…The higher than expected carcass value could be because of smaller particles in the bone marrow, suggesting the possibility of some agglomeration and deflocculation of 67 Ga‐particles in vivo . Cations, charged membranes, oxidants and alkaline salts are known to disturb the h ‐SnF 2 dispersion into larger and/or smaller particles in vitro . It is unlikely endogenous calcium or magnesium ions in blood is an explanation, because the tin fluoride particles are stable in that environment when 99m Tc is attached.…”

“…There were a very small differences observed in % RE and % RSPD when SnF 2 was diluted in saline or WFI before adding to [ 67 Ga(OAc) 3 ] under nitrogen (rxns 14, 15). There was a slight improvement in % RE when the saline diluted SnF 2 was filtered (0.2 μm) before addition to [ 67 Ga(OAc) 3 ], and the 67 Ga-particles were essentially >2.7 μm (rxns 15,16).…”

“…99m Tc-tin fluoride colloid particles are still used in the clinic for labelling autologous leucocytes ex vivo, the resulting 99m Tc-SnF 2 -leucocytes have shown high value in the assessment of inflammatory bowel disease. 14 The radiopharmaceutical chemistry of 99m Tc-tin fluoride colloid was reported previously in some detail, 15 in which these particles were characterised as containing O-Sn 2+ bonds for binding 99m Tc. The presence of anionic oxygen may be useful for coordinating other radiometals such as gallium ions.…”