Accumulation of 99mTc-low-density lipoprotein in human malignant glioma

Abstract

Summanr Low-density lipoprotein (LDL) uptake in gliomas was studied to find out if LDL has potential as a drug camrer of boron. especially for boron neutron capture therapy. Single photon emission tomography (SPET) was performed 2 h and 20 h after intravenous injection of autologous 9"9Tc-labelled LDL in four patients with untreated and five patients with recurrent glioma. 9'Tc-LDL uptake was compared with the uptake of 9'Tc-labelled human serum albumin (HSA). an established blood pool marker. The intra-and peritumoral distributions of radioactivity in the SPET images were not identical for radiolabelled LDL and HSA. The mean LDL tumour to brain ratio, determined from transversal SPET slices at 20 h post injection. was 1.5 in untreated and 2.2 in recurrent gliomas; the corresponding ratios for HSA were 1.6 and 3.4. The brain to blood ratio remained constant at 2 h and 20 h in both types of tumours. These data are not consistent with highly selective, homogeneous uptake of LDL in gliomas. However, the different tumoral distribution and rate of uptake of 9Tc-LDL, as compared with 9'Tc-HSA, indicate that the uptake of LDL is different from that of HSA and that further studies on the mechanism of LDL uptake in glioma are warranted.Keywords: brain neoplasm; glioma; radionucides: 'Tc-albumin: 'Tc-LDL Brain tumours, about half of which are gliomas, are among the ten most common human tumours (Fogeiholm et al., 1984; Cancer Society of Finland, 1992). More than half of the gliomas are malignant with a median survival time of about I year (Kalijo et al., 1991). In recent decades there has been no significant improvement in survival of patients with malignant glioma in spite of efforts to improve conventional treatments and to develop new ones. Boron neutron capture therapy (BNCT) is a relatively new binary therapy utilising low-energy neutrons and the neutron capture reaction of boron (Barth and Soloway, 1992). Gliomas have been treated with BNCI and are still the main target of research in this field (Barth and Soloway, 1992). BNCT requires sufficiently high and selective uptake of boron in the tumour tissue. The boronated agent mainly used in BNCT has been watersoluble borocaptate (BSH). The tumour to brain (T:Br) boron concentration ratios obtained with BSH have been rather low and are apparently dependent on blood flow (Dewit et al., 1990;Barth and Soloway, 1992;Haritz et al., 1994). Low-density lipoprotein (LDL), the main cholesterol carrier in blood, has been suggested as a more selective vehicle for boron since growing tumour tissue requires cholesterol for cell membrane synthesis (Kahl and Callaway,. 1989;Laster et al., 1991;Vitols, 1991).LDL is carried into the cell by a receptor-mediated mechanism (Brown and Goldstein, 1986). Leukaemic cells, lung cancers, brain tumours and glioma cell lines have LDL receptors (Murakami et al., 1990;Rudling et al., 1990;Vitols et al., 1990Vitols et al., , 1992 and LDL has been used for drug delivery in ovarian cancer therapy trials (Gal et al., 1981; Filipowska et al., 1992)....

Preparation of Tributyrin Emulsion and Characterization of the Binding of the Emulsion Particles to Low‐Density Lipoprotein in vitro

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Evaluation of the Pharmacokinetics of All-Trans-Retinoic Acid (ATRA) in Wistar Rats After Intravenous Administration of ATRA Loaded into Tributyrin Submicron Emulsion and its Cellular Activity on Caco-2 and HepG2 Cell Lines

“…21 Elevated LDL receptor levels were also reported in colon, kidney, liver tumors as well as in other tumor cells. [22][23][24] Because of its high expression in tumor cells, and its function as an internalizing receptor, LDL receptor becomes an attractive target for the selective delivery of anti-neoplastic drugs to tumors. The oil phase used in the lipid emulsion was tributyrin, which has synergistic effects with ATRA on carcinoma cells.…”

Synthesis and Evaluation of a Radioiodinated Tracer with Specificity for Poly(ADP-ribose) Polymerase-1 (PARP-1) in Vivo

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