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UNLABELLED This paper reports the development and application of intralesional targeted alpha therapy (TAT) for melanoma, being the first part of a program to establish a new systemic therapy. RATIONALE Labelling the benign targeting vector 9.2.27 with 213Bi forms the alpha-immunoconjugate (AIC), which is highly cytotoxic to targeted melanoma cells. (More)
Targeted alpha therapy (TAT) is an emerging therapeutic modality, thought to be best suited to cancer micrometastases, leukaemia and lymphoma. TAT has not been indicated for solid tumours. However, several melanoma patients in a phase 1 clinical trial of systemic targeted alpha therapy for melanoma experienced marked regression of subcutaneous and internal(More)
Purpose: The urokinase plasminogen activator (uPA) and its receptor (uPAR) are expressed by pancreatic cancer cells and can be targeted by the plasminogen activator inhibitor type 2 (PAI2). We have labeled PAI2 with 213Bi to form the alpha conjugate (AC), and have studied its in vitro cytotoxicity and in vivo efficacy. Methods and Materials: The expression(More)
Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for(More)
Mean values and standard deviations of total body volume, body density, height, weight, and a battery of 20 girth measurements of 200 Punjabi girls aged 10–19 years are presented. Selective stepwise multiple regression equations for predicting total body volume and body density from girth measurements are also given for different age groups. Hip girth was(More)
PURPOSE Control of ovarian cancer (OC) ascites remains a major objective in post-surgical treatment. The aim of this study was to investigate the effect of targeted alpha therapy (TAT) for the control of ascites in an OC ascites mouse model; the biodistribution of (213)Bi-C595 and its long term toxicity. METHODS The expression of tumor-associated antigen(More)
Ionizing radiation causes structural chromosomal aberrations, a proportion of which give rise to chromosome fragments without spindle attachment organelles. When a cell divides, some of these fragments are excluded from the main daughter nuclei and form small nuclei within the cytoplasm. The cytokinesis-block micronucleus assay allows these micronuclei (MN)(More)
The vectors PAI2, C595 and Herceptin target the membrane-bound uPA, MUC1 and HER2 antigens expressed by cancer cells, respectively. The expression of these receptors was tested in the ovarian cancer cell line OVCAR-3; MUC-1 was strongly expressed (3+), uPA moderately expressed (2+), but HER2 was negative (-). The alpha-emitting radionuclide Bismuth-213 was(More)
OBJECTIVES Key objectives of the study were to determine the pharmacokinetics and efficacy of the alpha emitting Bismuth-213 labeled 9.2.27 alpha-immunoconjugate (AIC). METHODS Balb/c nude mice were injected with varying doses of AIC to determine the pharmacokinetics of the AIC. The results were normalized to percent counts per minute (CPM) per gram per(More)
Bevacizumab, a humanized anti-VEGF monoclonal antibody has shown promise in various clinical trials. We report the development and testing of Bi-213 (an alpha-emitting radionuclide) labeled bevacizumab for in vitro and in vivo studies using two different chelators viz cDTPA and CHX-A''. The developed labeling method showed high labeling yields of 93.6% and(More)