Treatment of neuroblastoma meningeal carcinomatosis with intrathecal application of alpha-emitting atomic nanogenerators targeting disialo-ganglioside GD2.

Labeling of specific antibodies with bifunctional chelated Actinium-225 ((225)Ac; an alpha generator) allows the formation of new, highly potent and selective alpha-emitting anticancer drugs. We synthesized and evaluated a radioimmunoconjugate based on 3F8, an IgG(3) antibody that specifically binds to ganglioside GD2, which is overexpressed by many neuroectodermal tumors including neuroblastoma. The (225)Ac-1,4,7,10-tetra-azacylododecane (DOTA)-3F8 construct was evaluated for radiochemical purity and sterility, immunoreactivity, cytotoxicity in vitro, induction of apoptosis on GD2-positive cells, as well as for pharmacological biodistribution and metabolism of the (225)Ac generator and its daughters in a nude mouse xenograft model of neuroblastoma.

Alpha-particle emitting atomic generator (Actinium-225)-labeled trastuzumab (herceptin) targeting of breast cancer spheroids: efficacy versus HER2/neu expression.

Purpose: The humanized monoclonal antibody, trastuzumab (Herceptin), directed against HER2/neu, has been effective in the treatment of breast cancer malignancies. However, clinical activity has depended on HER2/neu expression. Radiolabeled trastuzumab has been considered previously as a potential agent for radioimmunotherapy.

Intralesional radioimmunotherapy with Yttrium-90-labeled human monoclonal IgM in nude mice bearing human tumor xenografts.

Unlabelled: Biodistribution studies demonstrate that intralesional administration of radiolabeled IgM results in high retention of radioactivity with little normal tissue uptake. This study examines the therapeutic potential of this modality.

Materials And Methods: Nude mice bearing subcutaneous human head and neck squamous cell carcinoma xenografts were treated with single intralesional (IL) injections of tumor-reactive human monoclonal IgM (CR4E8) labeled with 25-394 microCi of yttrium-90 (90Y).

Targeted actinium-225 in vivo generators for therapy of ovarian cancer.

Advanced ovarian cancer is largely incurable, but initially it is frequently confined to the i.p. space.