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Preparation and quality control of lutetium-177 bleomycin as a possible therapeutic agent

Yousefnia H., Jalilian A. R., Zolghadri S., Bahrami-Samani A., Shirvani-Arani S., Ghannadi-Maragheh M.

Nukleonika

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2010

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Vol. 55, No. 3

285-291

EN

Due to interesting therapeutic properties of 177Lu and antineoblastic antibiotic, bleomycin (BLM), 177Lu-bleomycin (177Lu-BLM) was developed as a possible therapeutic compound. Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of a natural Lu2O3 sample with a thermal neutron flux of 4 × 1013 nźcm-2źs-1. The product was converted into chloride form which was further used for labeling of BLM. In optimized conditions a radiochemical purity of 98% was obtained for 177Lu-BLM shown by instant thin-layer chromatography (ITLC) (specific activity, 740 GBq/mmole). Biodistribution studies of Lu-177 chloride and 177Lu-BLM were performed in wild-type rats. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a pattern similar to the other radiolabeled bleomycins. Lu-BLM is a possible therapeutic agent in human malignancies and the efficacy of the compound should be tested in various tumor-bearing models.

2

Theoretical Investigation of Molecular and Electronic Properties of 2,4'-Bithiazole Isomer in Bleomycin, an Antitumor Drug

Abedi A., Safari N., Bahrami H.

Polish Journal of Chemistry

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2009

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Vol. 83, nr 4

669-679

EN

Bithiazole moiety of bleomycin, a DNA cutting agent has been investigated using ab initio method. B3LYP/6-31G* level has been shown to be suitable for optimizing structural properties of bithiazole compounds. Mother nature has chosen the 2,4'-bithiazole isomer, which has interesting bioactivity. Other isomers such as 2,2c-bithiazole and 4,4'-bithiazole, which have similar structures and reactivity in vitro chemistry, were studied and compared with 2,4'-bithiazole isomer to find out what is special about this isomer in order to illustrate its bioactivity. These studies have confirmed that 2,4'-bithiazole isomeris more stable, its electron affinity is higher and has special electrostatic charac eristics compared to other isomers. These properties of 2,4'-bithiazole can be related to the roles of this part of drug in DNA cleavage.

3

Preparation and biological evaluation of [61Cu]bleomycin complex as a possible PET radiopharmaceutical in normal and fibrosarcoma-bearing animals

Jalilian A. R., Zandi H., Sardari D., Akhlaghi M., Kamali-Dehghan M., Shafaei K., Majdabadi A.

Nukleonika

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2009

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Vol. 54, No. 2

135-141

EN

[61Cu]bleomycin ([61Cu]BLM) was prepared using [61Cu]CuCl2 produced via natZn(p,x)61Cu. [61Cu]BLM was prepared under optimized conditions (room temperature, 45 min, 0.1 mg bleomycin for 92.5–370 MBq 61CuCl2) with radiochemical purity over 98% shown by HPLC and RTLC. [61Cu]BLM was administered into normal and tumor bearing rodents up to 210 min followed by biodistribution and co-incidence imaging studies. A significant tumor/non tumor accumulation was observed either by animal sacrification or an imaging method. [61Cu]BLM can be a potential PET radiotracer for tumor imaging.

4

Development of 62Zn bleomycin as a possible PET tracer

Jalilian A., Fateh B., Ghergherehchi M., Karimian A., Moradkhani S., Kamali-Dehghan M., Tabeie F.

Nukleonika

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2005

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Vol. 50, nr 4

143-148

EN

Abstract Bleomycin (BLM), labeled with radioisotopes, is widely used in therapy and diagnosis. In this study, BLM was labeled with 62Zn for oncologic PET studies. The complex was obtained at pH = 2 in saline at 90°C in 25 min. Radio-TLC showed an overall radiochemical yield of 95 97% (radiochemical purity > 97%). Stability of complex was checked in vitro in mice and human plasma/urine. Preliminary in vivo studies were performed to determine complex stability and distribution of 62Zn BLM in normal and fibrosarcoma-bearing mice. 62Zn BLM accumulated significantly in induced fibrosarcoma tumors in mice according to biodistribution/imaging studies. 62Zn BLM can be used in PET oncology studies due to its suitable physicochemical properties as a diagnostic complex in vitro and in vivo. Further studies should be performed for evaluation of the complex behavior in larger mammals.

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Comparison of the effects of bleomycin and ionizing radiation in two sublines of murine lymphoma L5178Y

Kruszewski M., Zaim J., Grądzka I., Szumiel I.

Nukleonika

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2001

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Vol. 46, nr 3

81-86

EN

We compared the effects of bleomycin (BLM) and ionizing radiation on two sublines of murine lymphoma L5178Y (LY): LY-R, radiation resistant and LY-S, radiation sensitive. This radiosensitivity difference is related to the ability to rejoin DNA double strand breaks. LY-S cells were about two times more sensitive to BLM than LY-R, similarly as in the case of sensitivity to X rays. Since there was no difference in the P-glycoprotein-related drug transport system between the sublines, it could be expected that the enhanced sensitivity of LY-S cells to BLM was caused by the DNA repair defect. Growth disturbances in BLM treated cell populations were proportional to the lethal effect and their duration was observed until elimination of dead cells (3-6 days after 50 ěM BLM, 1 h at 37oC). There was no slow growth phase accompanied by normal viability, as previously described for X-irradiated LY-S cells. Initial DNA damage, estimated with the single cell gel electrophoresis method was linearly related to BLM dose in LY-S cells; in LY-R cells - in the low dose range (up to 10 ěM) - there was more damage than in LY-S cells, however, at higher doses the dose - effect curves became identical. The doseeffect relationship for ă rays was linear and identical in both cell sublines. DNA damage distribution in BLM treated cells was much less uniform as compared to that in irradiated cells and indicated the presence of cells with severely damaged DNA, a feature typical for BLM action in vitro.