Scintigraphic evaluation of the pharmacokinetics of a soluble polymeric drug carrier (original) (raw)

1992, European Journal of Nuclear Medicine

There is a growing interest in the use of macro-Previous studies in our departments have identified, molecular carriers for therapeutic agents. If these carriers from a range of synthetic branched chain polymers can be labelled with an appropriate gamma-emitter, their based on a polylysine backbone, polypeptide "eak", biodistribution could be followed by scintigraphy. We containing glutamic acid at the side chain terminal posihave imaged the biodistribution of a synthetic branched tion (Fig. 1). This polymer has suitable biodistribution polypeptide, based on a poly-L-lysine backbone (average properties both unconjugated (Clegg et al. 1990a) or molecular mass 45 kDa). The polymer was conjugated to conjugated to anti-cancer drugs such as methotrexate diethylene triamine penta-acetic acid and labelled by and daunomycin (Clegg etal. 1990b; Hudecz et al. chelation with indium-111. Mice were injected i.v. with 1992). Blood kinetic studies carried out with this materilabelled material and imaged with a gamma-camera with al labelled with iodineq25 have shown that it survives a pin-hole collimator. Images showed the majority of well in the circulation. In those earlier studies (Clegg tracer remaining in the blood pool, but about 35% ap-et al. ]990a, b) the blood levels were determined in mice peared in the urinary bladder within 1.5 h. When the by sequential sampling of blood from the tail vein. There rain-polymer was fractionated by gel filtration chro-was an initial, short-lived (< 1 h), rapid loss of some matography on S-300, the imaging showed that the early material from the blood, followed by a slower clearance eluting material was retained, the intermediate showed of the majority of the material. However, such repeated some renal clearance, and the late was rapidly excreted, blood sampling cannot give adequate numbers of data These findings show the value of gamma-scintigraphy for points for precise short-term blood pharmacokinetics, biodistribution studies with such polymeric drug carriers and without the sacrifice and dissection of groups of and its potential for clinical pharmacokinetic studies, animals at numerous time points, the site of clearance of material from the blood cannot be determined. Clear-Key words: Scintigraphy Polymers Biodistribution ly, this is a situation in which scintigraphy should be able to provide a valuable insight into the pharmacokin-Eur J Nucl Med (1992) 19:449-452 etics of this material. We have previously shown that it is possible to label this polymer with indium-ill, by diethylene triamine tetra-acetic acid (DTPA) chelation (Pimm et al. 1992).