REPEAT INJECTION STUDIES OF TC-99M-LABELED PEG-LIPOSOMES IN THE SAME ANIMAL

This study was designed to determine if repeat injections of polyethyl ene glycol (PEG) coated liposomes in the same animal lead to a change in biodistribution due to a biological response. To evaluate the long- term storage of PEG-liposomes for imaging applications and to remove a ny concerns of batch variability, one large batch of PEG-liposomes con taining glutathione and sucrose was prepared and used for the entire s tudy. On each day that an imaging study was performed, an aliquot of P EG-liposomes were labeled with technetium-99m (Tc-99m) using hexamethy lpropyleneamine oxime. Rabbits (n = 4) were injected with Tc-99m-PEG-l iposomes (2 ml; 13 mg phospholipid/kg body wt; 2 mCi Tc-99m-activity) at 8 days after manufacture and imaged under a gamma camera. Heart-to- lung ratios, heart-to-liver ratios and organ activities were determine d by region of interest analysis. Blood samples were collected to gene rate blood clearance curves. Six weeks later the same rabbits were giv en a second dose of Tc-99m-PEG-liposomes at 50 days after manufacture and imaged as before. A set of new rabbits (n = 3) were also imaged at six weeks using Tc-99m-PEG-liposomes in order to differentiate any di fferences in organ distribution due to storage vs, reinjection. Images acquired for each set of rabbits at 30 minutes demonstrated little ch ange in organ distribution following reinjection. Heart-to-lung ratios decreased from 2.25 +/- 0.06 at baseline to 2.05 0.05 on reinjection and 2.10 +/- 0.01 upon storage. Heart-to-liver ratios were 1.46 +/- 0. 06 on reinjection, significantly lower than the ratio of 1.72 +/- 0.10 at baseline or 1.68 +/- 0.09 upon storage. Circulation half-life of 2 9 hours did not change within the three groups. Although a slight chan ge in organ biodistribution occurred with storage and reinjection, the se effects were minimal and are not likely to affect drug targeting or diagnostic imaging on repeat injection.