Abstract
To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (68Ga/64Cu) and therapy (177Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which 177Lu-L1 exhibited markedly higher uptake in HeLa cells than the 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of 68Ga-L1 and 64Cu-L1 was clearly visualized in the tumor site, while 177Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when 68Ga-L1 or 64Cu-L1 is used for diagnosis, 177Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other.
Keywords:
177Lu; 64Cu; 68Ga; benzothiazole; radiopharmaceuticals.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aniline Compounds / administration & dosage*
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Aniline Compounds / chemistry
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Animals
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Benzothiazoles / administration & dosage*
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Benzothiazoles / chemistry
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Copper Radioisotopes / administration & dosage
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Copper Radioisotopes / chemistry
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Female
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Gallium Radioisotopes / administration & dosage
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Gallium Radioisotopes / chemistry
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HEK293 Cells
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HeLa Cells
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Heterocyclic Compounds, 1-Ring / administration & dosage*
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Heterocyclic Compounds, 1-Ring / chemistry
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Humans
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Lutetium / administration & dosage
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Lutetium / chemistry
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Positron-Emission Tomography / methods
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Radioisotopes / administration & dosage
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Radioisotopes / chemistry
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Radiopharmaceuticals / administration & dosage*
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Radiopharmaceuticals / chemistry
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Theranostic Nanomedicine / methods*
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Treatment Outcome
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Uterine Cervical Neoplasms / diagnostic imaging
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Uterine Cervical Neoplasms / therapy
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Xenograft Model Antitumor Assays
Substances
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1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid
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Aniline Compounds
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Benzothiazoles
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Copper Radioisotopes
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Copper-64
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Gallium Radioisotopes
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Heterocyclic Compounds, 1-Ring
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Radioisotopes
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Radiopharmaceuticals
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Lutetium
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Gallium-68
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Lutetium-177