PLASMA KINETICS AND BIODISTRIBUTION OF A LIPID EMULSION RESEMBLING LOW-DENSITY-LIPOPROTEIN IN PATIENTS WITH ACUTE-LEUKEMIA

Low-density lipoprotein (LDL) could be used as a carrier of chemothera peutic agents to neoplastic cells that overexpress LDL receptors (rLDL ), but LDL is difficult to obtain and handle. Recently, it was observe d that a protein-free emulsion resembling the lipid portion of LDL (LD E) behave like native LDL when injected into the bloodstream. In this study, the evidence that LDE is taken up by rLDL was expanded by compa ring LDL and LDE plasma decay curves in rabbits and by competition exp eriments with lymphocytes. To verify whether LDE could be removed from the plasma by neoplastic cells with increased rLDL, LDE labeled with (14)Ccholesteryl ester was injected into 14 patients with acute myeloi d leukemia (AML) and into 7 with acute lymphocytic leukemia (ALL). In AML rLDL expression is increased but in ALL it is normal. LDE plasma f ractional clearance rate (FCR, in h(-1)) was calculated from the remai ning radioactivity measured in plasma samples collected during 24 h fo llowing injection. LDE FCR was 3-fold greater in AML than in ALL patie nts 0.192 +/- 0.210 (SD) and 0.066 +/- 0.033 h(-1), respectively, P < 0.035. When LDE injection was repeated in 9 AML patients in hematologi cal remission, LDE FCR diminished 66% compared to the pretreatment val ues (from 0.192 +/- 0.210 to 0.065 +/- 0.038 h(-1), P < 0.02), so that it could he estimated that nearly 66% of the emulsion was taken up by AML cells and only 34% by the normal tissues. As expected, LDE FCR wa s unchanged in 4 patients with ALL in hematological remission (0.069 /- 0.044 h(-1)). Gamma camera images obtained 6 h after the injection of Tc-99m-labeled LDE into one patient with ALL shelved biodistributio n similar to that of LDL. In one AML patient LDE was comparatively mor e concentrated over the areas corresponding to the hone marrow infiltr ated by AML cells. Our results indicate that LDE FCR is increased in a disease known to contain malignant cells that overexpress rLDL, sugge sting that LDE is taken up by malignant cells with increased rLDL.