Preparation and preliminary biological evaluation of a 177Lu labeled sanazole derivative for possible use in targeting tumor hypoxia.

Abstract

The preparation of a polyazamacrocyclic-nitrotriazole conjugate for radiolabeling with the therapeutic radioisotope viz. (177)Lu is described. The nitroimidazole used for the present study is [N-2'(carboxyethyl)-2-(3'-nitro-1'-triazolyl)acetamide], the carboxylic acid derivative of sanazole, which possesses an optimal combination of desired properties such as, selective toxicity for hypoxic cells, lowered lipophilicity resulting in lowered neurotoxicity. The bifunctional chelating agent is a DOTA derivative viz. 1,4,7,10-tetraaza-1-(4'-aminobenzylacetamido)-cyclododecane-4,7,10- triacetic acid (p-amino-DOTA-anilide). (177)Lu was produced in adequate specific activity (110TBq/g) and high radionuclidic purity (approximately 100%) by irradiating enriched (60.6% (176)Lu) Lu(2)O(3) target and used for radiolabeling of the sanazole-BFCA conjugate. approximately 98% Complexation yield was achieved under optimized conditions. The complex has been characterized by paper chromatography and HPLC studies. Bioevaluation studies in Swiss mice bearing fibrosarcoma tumors revealed moderate tumor uptake (0.88%/g at 1h post-injection) with favorable tumor to blood (4.00 at 1h post-injection) and tumor to muscle (4.63 at 1h post-injection) ratios.

• Authors: Tapas Das, Sudipta Chakraborty, Sharmila Banerjee, Archana Mukherjee, Grace Samuel, H D Sarma, C K K Nair, V T Kagiya, Meera Venkatesh
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 12 Issue 23 Pg. 6077-84 (Dec 01 2004) ISSN: 0968-0896 [Print] England
• PMID: 15519153 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Radioisotopes
• Radiopharmaceuticals
• Triazoles
• AK 2123
• Lutetium

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacokinetics)
• Drug Delivery Systems
• Fibrosarcoma (metabolism, radiotherapy)
• Hypoxia (radiotherapy)
• Lutetium (therapeutic use)
• Mice
• Neoplasms (metabolism, radiotherapy)
• Radioisotopes (therapeutic use)
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics, therapeutic use)
• Tissue Distribution
• Triazoles (pharmacology, therapeutic use)