Effect of liposome surface charge on the stability of technetium (99mTc) radiolabelled liposomes

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Abstract
Using liposomes radiolabelled by the 99mTechnetium-stannous chloride technique we have investigated the effect of surface charge on the stability of the isotope in vitro and in vivo. Dialysis of 99mTc-labelled positive, negative and neutral liposomes, which had been incubated in either saline or normal rat serum showed no significant loss of the isotope from the liposome surface with only 2 per cent of the isotope dialysed. A comparison of gel chromatography with dialysis confirmed that most of the isotope remained attached to the liposome surface, but it did reveal greater loss of the isotope, between 15 and 23 per cent. the liposome clearance rates obtained from 125I-egg phosphatidylcholine (EPC) and 99mTc dual-labelled positive or neutral liposomes were significantly different. the 99mTc marker was cleared five times faster from the positive liposomes and twice as fast from the neutral liposomes as the 125I-EPC integral membrane marker. the 99mTc attached to liposomes with a negative surface charge was stable in vivo and had the same clearance rate from the circulation as the 125I-EPC marker. These results indicate that the commonly used in vitro techniques for assessing liposome radiolabel stability are unsuitable for predicting the stability of the 99mTc in vivo.