title: Biological evaluation of new potential anticancer agent for tumour imaging and radiotherapy by two methods:99mTc-radiolabelling and EPR spectroscopy.
abstract: Recently, a new class of in vitro and ex vivo radiotracers/radioprotectors, the nitroxyl-labelled agent 1-ethyl-1-nitroso-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-urea (SLENU), has been discovered. Our previous investigations demonstrated that SLENU is a low-molecular-weight stable free radical which is freely membrane permeable, easily crosses the blood brain barrier and exhibited in/ex vivo the lowest general toxicity and higher anticancer activity against some experimental tumour models. Further investigation was aimed to develop a99mTc-labelled SLENU (97%) as a chelator and evaluate its labelling efficiency and potential use as a tumour seeking agent and for early diagnosis. Tissue biodistribution of99mTc-SLENU was determined in normal mice at 1, 2 and 24 h (n= 4/time interval, route of administration i.v.). The distribution data were compared using male albino non-inbred mice and electron paramagnetic resonance investigation. The imaging characteristics of99mTc-SLENU conjugate examined in BALB/c mice grafted withEhrlich Ascitis tumourin the thigh of hind leg demonstrated major accumulation of the radiotracer in the organs and tumour. Planar images and auto-radiograms confirmed that the tumours could be visualized clearly with99mTc-SLENU. Blood kinetic study of radio-conjugate showed a bi-exponential pattern, as well as quick reduced duration in the blood circulation. This study establishes nitroxyls as a general class of new spin-labelled diagnostic markers that reduce the negative lateral effects of radiotherapy and drug damages, and are appropriate for tumour-localization.
authors.affiliation: Department of Chemistry and Biochemistry, Medical Faculty, Trakia University , 11 Armeiska Street, 6000 Stara Zagora , Bulgaria ; Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences , Brig S.K. Mazumdar Marg, Delhi 110054 , India ; Institute of Nuclear Medicine and Allied Sciences , Brig S.K. Mazumdar Marg, Delhi 110054 , India.
authors.forename: Yanka
authors.initials: Y
authors.lastname: Karamalakova
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences , Brig S.K. Mazumdar Marg, Delhi 110054 , India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences , Brig S.K. Mazumdar Marg, Delhi 110054 , India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Chemistry and Biochemistry, Medical Faculty, Trakia University , 11 Armeiska Street, 6000 Stara Zagora , Bulgaria.
authors.forename: Antoaneta
authors.initials: A
authors.lastname: Zheleva
authors.affiliation: Department of Chemistry and Biochemistry, Medical Faculty, Trakia University , 11 Armeiska Street, 6000 Stara Zagora , Bulgaria.
authors.forename: Veselina
authors.initials: V
authors.lastname: Gadjeva
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences , Brig S.K. Mazumdar Marg, Delhi 110054 , India.
authors.forename: Anil
authors.initials: A
authors.lastname: Mishra
keywords: 99mTc-conjugate; EAT tumour; SLENU; biodistribution; ex vivo EPR; tumour imaging