Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes

The biodistribution and pharmacokinetics of In-111-DTPA-labeled pegylated l iposomes (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 t(1/2 beta) 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 glio ma, and 1 of 1 cervix cancer). The levels of tumor liposome uptake estimate d 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 i n 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 intermediat e 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 mirrore d the estimated tumor volumes of the various tumor types (36.2 +/- 18.0 cm( 3) for squamous cell cancer of the head and neck, 114.5 +/- 42.0 cm(3) for lung tumors, and 234.7 +/- 101.4 cm(3) for breast tumors), In addition, sig nificant localization of the liposomes was seen in the tissues of the retic uloendothelial system (liver, spleen, and bone marrow). One patient with ex tensive mucocutaneous AIDS-related Kaposi sarcoma was also studied accordin g to a modified protocol, and prominent deposition of the radiolabeled lipo somes was demonstrated in these lesions. An additional two patients with re sectable head and neck cancer received 26 MBq of IDLPL 48 h before undergoi ng 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 tu mor uptake exceeding that in normal mucosa by a mean ratio of 2.3:1, in ski n by 3.6:1, in salivary gland by 5.6:1, in muscle by 8.3:1, and in fat by 1 0.8:1, These data strongly support the development of pegylated liposomal a gents for the treatment of solid tumors, particularly those of the head and neck.