Successful imaging of human cancer with indium-111-labeled phospholipid vesicles

Abstract

Twenty-four patients with proven primary and/or metastatic cancer received single intravenous injections of phospholipid vesicles containing 0.5 mCi of Indium-111. Gamma camera scintigraphy 1 to 72 hours later visualized tumors in 22 patients (92%), including carcinomas of breast, lung, colon, prostate, kidney, cervix, thyroid, and soft tissue sarcoma, lymphoma, and melanoma. Tumor sites that were identified included soft tissues, bone, lung, liver, lymph node, and spinal cord. There were only two false-positive images in metastatic sites and four false-negative images in metastatic sites. Overall sensitivity for tumors in 97 individual sites was 85%, whereas specificity was 96%. Unsuspected areas of malignancy were seen in the lumbar subdural space, pleura, liver, thyroid, and lung. Besides tumor accumulations, homogeneous uptake was observed in normal liver and spleen. Radiation doses to these two organs were 2.2 and 2.9 cGy/0.5 mCi In-111, respectively. Whole body radiation dose was 0.3 cGy/0.5 mCi. The use of Indium-111-labeled vesicles permits a wide variety of human tumors in primary and metastatic sites to be imaged without toxicity and with radiation doses comparable to other radionuclide scanning techniques.

Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes.

“…Successful therapy requires the site-specific delivery of relatively large amounts (15)(16)(17)(18)(19)(20) jig of B per g of tissue) of boron to tumors (2). Strategies employed have included the use of boron compounds with some natural affinity for tumors, such as 4-(dihydroxyboryl)phenylalanine (BPA) (3) or the mercaptoundecahydro-closo-dodecaborate dianion (B12H,,SH2-; BSH) (4); the attachment ofboron-containing species to other molecules such as porphyrins (5); and the conjugation of boron-rich compounds with tumor-specific monoclonal antibodies and their fragments (6).…”

“…Previous research, utilizing pure synthetic phospholipids, has produced useful unilamellar vesicles that have been shown to deliver their contents preferentially to tumor cells in animals (11,14) and humans (15,16) such that the tumor levels of effector molecules are 5-10 times that of normal tissue, including blood.…”

Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy.

“…Animal studies have shown that liposomes can decrease the toxicity of several antitumnor and antifungal drugs, leading to several recent clinical trials with promising results (2)(3)(4)(5)(6). In addition, liposomes have been shown to be efficient carriers of antiparasitic drugs for treating intracellular infections of the reticuloendothelial system (RES), in activating macrophage cells to become tumoricidal in models of metastasis, and in enhancing the immune response to encapsulated antigens, thus facilitating the formulation of artificial vaccines (7,8).…”

Positron Emission Tomography Based Elucidation of the Enhanced Permeability and Retention Effect in Dogs with Cancer Using Copper-64 Liposomes

“…[15][16][17][18] The tumor accumulation levels of [Cu-64]-liposomes in the included carcinomas that displayed EPR effects (based on increasing accumulation between scans) are compatible to those reported in previous human cancers evaluated by gamma camera and SPECT imaging. 15 The authors report tumor uptake from tumor size estimations to range from 2.7 -53.0 %ID/kg.…”

“…Current knowledge on the EPR-effect in human tumors is based on studies of low-resolution single photon imaging techniques of radiolabeled liposomes. [15][16][17][18] Liposome uptake has been investigated in a Kaposi sarcoma and a lymphoma patient. 16 Furthermore, targeting and delineation has been investigated in eight high-grade gliomas 17 and positive tumor identification using radiolabeled phospholipid vesicles in 22 of 24 patients suffering from a few malignancies.…”