A comparison of biodistribution of liposomal and soluble IL-2 by a new method based on time-resolved fluorometry of europium.
A novel method was developed to determine the pharmacokinetics and biodistribution of cytokines and lymphokines based on time-resolved fluorometry (TRF) of europium (Eu). The comparison of two formulations of IL-2 was used to illustrate the sensitivity and applicability of this method as well as to extend the information on the pharmacokinetics of liposomal IL-2 and soluble IL-2. The blood kinetics and biodistribution of liposomal and soluble IL-2 in lymphoid organs and kidneys as measured by TRF were similar to those determined by the radioisotopic method. In both instances, the formulation of IL-2 into liposomes increased its serum half-life and accumulation in reticuloendothelial and lymphoid organs. The increased sensitivity of the Eu/TRF method permitted the extension of observational time points and the analysis of biodistribution in organs such as lymph nodes and bone marrow. These results suggest that Eu-labelled proteins in conjunction with TRF offer a suitable alternative to radiolabelled proteins for pharmacokinetics and tissue distribution studies in animals. This method offers distinct advantages over traditional techniques employing radioistopes since it has greater sensitivity, no half-life limitations and no radioactive or hazardous waste disposal.
Neville
M E
ME
Research and Development Department, Biomira USA Inc, Cranbury, NJ, USA.
Richau
K W
KW
Boni
L T
LT
Pflug
L E
LE
Robb
R J
RJ
Popescu
M C
MC
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005063:Europium / Q000378:metabolism*; D005260:Female; D005470:Fluorometry / Q000379:methods*; D006801:Humans; D007376:Interleukin-2 / Q000097:blood* / Q000493:pharmacokinetics*; D008081:Liposomes / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D012680:Sensitivity and Specificity; D013997:Time Factors; D014018:Tissue Distribution
D007376:Interleukin-2; D008081:Liposomes; D005063:Europium