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Imperial Cancer Research Fund, Oncology Unit [K. J. H., R. G. V.], and Department of Imaging [S. M., D. G., A. M. P.], Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London W12 0HS, United Kingdom; Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55902 [K. J. H., R. G. V.]; SEQUUS Pharmaceuticals Incorporated, Menlo Park, California 94025 [P. S. U.]; and Department of Radiotherapy, Charing Cross Hospital, London W6 8RP, United Kingdom [J. S. W. S.]
The biodistribution and pharmacokinetics of 111In-DTPA-labeled pegylated liposomes (IDLPL) were studied in 17 patients with locally advanced cancers. The patients received 65–107 MBq of IDLPL, and nuclear medicine whole body gamma camera imaging was used to study liposome biodistribution. The t1/2ß of IDLPL was 76.1 h. Positive tumor images were obtained in 15 of 17 studies (4 of 5 breast, 5 of 5 head and neck, 3 of 4 bronchus, 2 of 2 glioma, and 1 of 1 cervix cancer). The levels of tumor liposome uptake estimated from regions of interest on gamma camera images were approximately 0.5–3.5% of the injected dose at 72 h. The greatest levels of uptake were seen in the patients with head and neck cancers [33.0 ± 15.8% ID/kg (percentage of injected dose/kg)]. The uptake in the lung tumors was at an intermediate level (18.3 ± 5.7% ID/kg), and the breast cancers showed relatively low levels of uptake (5.3 ± 2.6% ID/kg). These liposome uptake values mirrored the estimated tumor volumes of the various tumor types (36.2 ± 18.0 cm3 for squamous cell cancer of the head and neck, 114.5 ± 42.0 cm3 for lung tumors, and 234.7 ± 101.4 cm3 for breast tumors). In addition, significant localization of the liposomes was seen in the tissues of the reticuloendothelial system (liver, spleen, and bone marrow). One patient with extensive mucocutaneous AIDS-related Kaposi sarcoma was also studied according to a modified protocol, and prominent deposition of the radiolabeled liposomes was demonstrated in these lesions. An additional two patients with resectable head and neck cancer received 26 MBq of IDLPL 48 h before undergoing surgical excision of their tumors. Samples of the tumor, adjacent normal mucosa, muscle, fat, skin, and salivary tissue were obtained at operation. The levels of tumor uptake were 8.8 and 15.9% ID/kg, respectively, with tumor uptake exceeding that in normal mucosa by a mean ratio of 2.3:1, in skin by 3.6:1, in salivary gland by 5.6:1, in muscle by 8.3:1, and in fat by 10.8:1. These data strongly support the development of pegylated liposomal agents for the treatment of solid tumors, particularly those of the head and neck.
Commentary
Clin. Cancer Res. 2001 7: 223-225.
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