astatine and astato-2-methyl-1-4-naphthoquinol-diphosphate

6-[211At]-astato-MNDP is of a class of a high linear energy transfer endoradiotherapeutic drug, which selectively targets to an onco-APase isoenzyme expressed by certain epithelial and germ cell tumors. The therapeutic efficacy and acute toxicity of its endogenous alpha-particle emissions have been studied in a murine tumor model.. 211At was produced by the 207Bi(alpha,2n)211 At cyclotron-based nuclear reaction. High specific activity 6-[211At]-astato-MNDP was rapidly synthesized by in vacuo thermal heterogeneous isotopic exchange. The therapeutic potential of 6-[211At]-astato-MNDP and 211At- was determined in mice bearing a transplanted CMT-93 rectal carcinoma which exhibited onco-APase activity.. Significant therapeutic effects due to targeted alpha-particle emissions have been confirmed for the activity dose range, 10-750 kBq 6-[211At]-astato-MNDP. A therapeutic window has been identified, whereby cure rates of approximately 45-65% were achieved following administration of 55-300 kBq 6-[211At]-astato-MNDP. Estimated tumor absorbed radiation doses were not inconsistent with clinical response. Irreversible hematoxicity or stigmata of acute radiation damage in other critical normal tissues were not encountered. Nonspecifically internalized 211At- exerted no therapeutic effect.. Therapeutic results for 6-[211At]-astato-MNDP have confirmed the profound in vivo cytotoxicity of its targeted alpha-radiations in the CMT-93 tumor. Acute normal tissue toxicity was acceptable. A rationale for optimal fractionation of targeted 6-[211At]-astato-MNDP endoradiotherapy is discussed, and its putative role in the possible individualized management of certain human tumors has been proposed.

Topics: Adenocarcinoma; Animals; Astatine; Brachytherapy; Energy Transfer; Leukocyte Count; Male; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Rectal Neoplasms; Vitamin K; Vitamin K 3

The microscopic distribution of the potential endoradiotherapeutic drug, 6-[211At]-astato-2-methyl-1,4- naphthoquinol bis (diphosphate salt) in normal tissues of the mouse has been studied by alpha-particle track autoradiography. The uptake into critical radiosensitive tissues, especially bone marrow, colon and lung, was low.

Topics: Animals; Antineoplastic Agents; Astatine; Autoradiography; Bone Marrow; Colon; Lung; Male; Mice; Mice, Inbred C57BL; Rats; Tissue Distribution; Vitamin K; Vitamin K 3

6-[211At]astato-MNDP is currently being investigated as a potential high LET endoradiotherapeutic drug. Biodistribution and whole-body radiation retention studies have been carried out with 6-[211At]astato-MNDP and 211At- in a murine rectal tumour model; results indicate that the 211At-C bond in the compound is metabolically stable for at least 6 h. The Mean Biological Concentration of 6-[211At]astato-MNDP in tumour tissue ranged from 170-253% over an initial 12 h period; this was higher than that observed for the [211At]astatide anion. Conversely, the uptake of compound into radiobiologically critical organs was significantly lower.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Astatine; Female; Male; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Rectal Neoplasms; Tissue Distribution; Vitamin K; Vitamin K 3

A potential endoradiotherapeutic drug, 6-211At-astato-2-methyl-1,4-naphthoquinol bis (diphosphate salt), incorporating the alpha-emitting radio-halogen astatine-211 of half-life 7.2 h, is shown to be valuable for localization studies by means of alpha-particle track autoradiography in malignant and normal cells and tissues in the mouse with transplanted adenocarcinoma of the rectum.

Topics: Adenocarcinoma; Alpha Particles; Animals; Antineoplastic Agents; Astatine; Autoradiography; Colon; Lung; Male; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Neoplasms, Experimental; Rectal Neoplasms; Spleen; Subcellular Fractions; Vitamin K; Vitamin K 3

Topics: Alpha Particles; Antineoplastic Agents; Astatine; Cells, Cultured; Humans; In Vitro Techniques; Vitamin K; Vitamin K 3