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Uptake of a Cholesterol-Rich Emulsion by Breast Cancer

2002; Elsevier BV; Volume: 85; Issue: 3 Linguagem: Inglês

10.1006/gyno.2002.6654

1095-6859

Silvia Graziani, Fernando Igreja, Roberto Hegg, Cláudio Meneghetti, Laura I. Brandizzi, Renato Barboza, R.F. Amâncio, José Aristodemo Pinotti, Raul C. Maranhão,

Estrogen and related hormone effects

Overexpression of low-density lipoprotein (LDL) receptors occurs in several cancer cell lines and offers a unique strategy for drug targeting by using LDL as vehicle. However, the native lipoprotein is difficult to obtain and handle. Previously, we showed that a lipidic emulsion (LDE) similar to the lipid structure of native LDL may bind to LDL receptors and be taken up by acute myelocytic leukemia cells. We also showed that LDE can also concentrate in ovarian cancer tissue. In this study, we tested whether LDE is taken up by breast carcinoma.LDE labeled with (99m)Tc was injected into 18 breast cancer patients, and nuclear medicine images of the tumor and metastatic sites were acquired. Subsequently, LDE labeled with [3H]cholesteryl oleate was intravenously injected into 14 breast cancer patients 24-30 h before total mastectomy procedure. Fragments of normal and of breast cancer tissue excised during surgery were lipid extracted with chloroform/methanol and their radioactivity was measured in a scintillation solution.(99m)Tc-LDE images of the primary tumor and of metastasis sites were obtained in all 18 breast cancer patients. As directly measured in the tumor and in the normal mammary tissue, the amount of the emulsion radioactive label in the tumor was 4.5 times greater than in the normal tissue (range 1.2- to 8.8-fold).LDE concentrates much more in malignant breast tumor tissue than in the normal tissue. Thus it has potential to carry drugs or radionuclides directed against mammary carcinoma cells for diagnostic or therapeutic purposes.