title: 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.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: Tapas
authors.initials: T
authors.lastname: Das
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
authors.forename: Archana
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Grace
authors.initials: G
authors.lastname: Samuel
authors.forename: H D
authors.initials: HD
authors.lastname: Sarma
authors.forename: C K K
authors.initials: CK
authors.lastname: Nair
authors.forename: V T
authors.initials: VT
authors.lastname: Kagiya
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005354:Fibrosarcoma / Q000378:metabolism / Q000532:radiotherapy; D000860:Hypoxia / Q000532:radiotherapy*; D008187:Lutetium / Q000627:therapeutic use*; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D011868:Radioisotopes / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D014230:Triazoles; C072690:AK 2123; D008187:Lutetium