No abstract

Liposomes (phospholipid vesicles) have been proposed as carriers of materials of therapeutic interest, and work in this area has been reviewed (Tyrrell et al., 1976). The possibility of utilizing such a system in tumour therapy has received some attention, and Gregoriadis et al. (1974) injected patients with liposomes using entrapped l 3 I Ilabelled albumin as a marker. Tissue distribution was measured post mortem, several days after administration. As a more versatile alternative we have been investigating the use of the yemitter 9 9 m T~ (technetium) to study liposome distribution in experimental animals. This isotope has been found ideal for radioisotope imaging. Technetium, as the pertechnetate ion (99mT~04-), has previously been used as a vesicle marker to follow the short-term fate of liposomes in mice (McDougall et al., 1975), erythrocyte 'ghosts' in rats (Tyrrell & Ryman, 1976) and to follow liposome uptake by cells in tissue culture (Dunnick et al., 1976).We have prepared liposomes from combinations of the following purified lipids; phosphatidylcholine (egg lecithin), cholesterol, dicetyl phosphate and stearylamine.Rotary-evaporated lipid films were shaken with sterile 0.9 % NaCl to give a final suspension of 20% (w/v). These were surrounded by an ice bath and sonicated with a titanium probe( 1 .Ocm diameter)for20 bursts (6,um peak-to-peak) of ~O S , with 30 scoolingbetween. Technetium label was attached to these pre-formed liposomes by an SnCI, method. To the liposomes (600mg in 3.0ml) was added 0.5ml of a sterile neutral solution of 3m-SnClz previously prepared in 02-free water and stored under Nz at 4°C. The mixture was shaken well and not more than 2.5ml of sodium pertechnetate solution in 0.9% NaCl was added to the suspension, drop by drop, with vigorous shaking, and left at room temperature for 15-30min before injection. The presence of free pertechnetate was estimated by dialysis and found to be less than 2%.The possibility that a labelled SnCI, colloid was formed in the preparation of liposome batches was explored. A preparation with NaCI, SnCI, and pertechnetate formed a labelled colloid under the conditions of the labelling used for the liposomes, and this label could be removed by centrifugation at 4000rev./min for 5min in an MSE Super Minor bench centrifuge. Liposomes labelled under the same conditions remained in the supernatant. The contamination of technetium-labelled liposomes with free pertechnetate and colloid was therefore minimal.Liposomes (20mg of lipid) labelled with 1 mCi of 99mTc were injected into the tail vein of normal Wistar rats. Tissue distribution and clearance of the label from the blood was studied at various times by killing the animals and counting individual organs for radioactivity. Immediately before killing, a picture of the distribution of radioactivity in the whole animal was obtained by a y-camera-computer system (scintiscan). This provided a photographic image and a quantitative radioactivity distribution map for each rat.For the tumour studies, Wistar rats we...

1. With this method of investigation it appears that compression stockings have no value in preventing venous thrombosis after operation. 2. Clinical diagnosis is unreliable in detecting the presence of deep‐vein thrombosis. 3. We have confirmed that the incidence of deepvein thrombosis after operation is of the order of 30–35 per cent.

The possible use of liposomes (phospholipid vesicles) to direct cytotoxic drugs to tumours has led us to investigate the tissue localization of i.v. injected 99m-Tc-labelled liposomes in cancer patients. Twenty mg or 300 mg doses of liposomal lipid (7:2:1 molar ratio of phosphatidylcholine : cholesterol : phosphatidic acid) were used in a study of 13 patients with advanced cancer and one with polycythaemia rubra vera (PRV). In all cases except the patient with PRV the major site of uptake of the label was the liver and spleen. In the patient with PRV the liver uptake was greatly reduced and the major site of uptake was found in regions corresponding to marrow. With the exception of one patient with a primary hepatoma, there was no significant tumour uptake of the label. Images Fig. 2 Fig. 3

No abstract