Elevated uptake of low density lipoproteins by human lung cancer tissue in vivo.
In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. Previous in vitro and in vivo studies have shown that acute myelogenous leukemia cells have elevated receptor-mediated uptake of low density lipoproteins (LDL), compared to normal WBC. High receptor-mediated uptake of LDL by certain cancer cells in tissue culture and experimental tumors in animals in vivo has also been demonstrated. The present study was undertaken to compare the in vivo assimilation of LDL by human lung cancer tissue with that by surrounding lung tissue. Ten patients with newly diagnosed lung tumors, scheduled for surgery, received an i.v. injection of [14C]sucrose-labeled LDL. Following cellular uptake and degradation of the LDL particle, the radiolabeled sucrose moiety remains trapped in the lysosomal compartment, making this labeling technique useful for in vivo studies of tissue uptake of LDL. Radioactivity was determined in plasma and in tissue biopsies obtained at surgery 1-3 days after injection. The uptake of radioactivity in lung cancer tissue was elevated (1.5-3.0-fold), compared to surrounding tissue, in 7 of 9 patients with primary lung cancer. The most rapid preoperative disappearance of radioactivity from plasma was found in 2 patients with large tumors exhibiting high LDL uptake, relative to normal lung tissue. These findings support the hypothesis that the selectivity of cytotoxic agents can be enhanced also in nonhematological malignancies by administering the drugs incorporated in LDL particles.
Vitols
S
S
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
Peterson
C
C
Larsson
O
O
Holm
P
P
Aberg
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008077:Lipoproteins, LDL / Q000009:adverse effects / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013395:Sucrose / Q000009:adverse effects / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D008077:Lipoproteins, LDL; D013395:Sucrose