Copper-64-diacetyl-bis (N4-methylthiosemicarbazone) accumulates in rich regions of CD133+ highly tumorigenic cells in mouse colon carcinoma

Yoshii, Yukie; Furukawa, Takako; Kiyono, Yasushi; Watanabe, Ryoji; Waki, Atsuo; Mori, Tetsuya; Yoshii, Hiroshi; Oh, Myungmi; Asai, Tatsuya; Okazawa, Hidehiko; Welch, Michael J.; Fujibayashi, Yasuhisa

doi:10.1016/j.nucmedbio.2009.12.011

Cited by 40 publications

(37 citation statements)

References 39 publications

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“…This tracer shows favorable kinetics with rapid uptake in hypoxic tissue and fast clearance from normoxic tissues, enabling imaging within 30 min after injection [66,67] . However, the exact uptake mechanism of [Cu]ATSM is still under debate [63,68,69] and several preclinical studies have shown that [Cu]ATSM uptake depends on tumor type and other characteristics than hypoxia alone [70][71][72][73][74][75][76] .…”

Section: F]fmisomentioning

confidence: 99%

Positron emission tomography to assess hypoxia and perfusion in lung cancer

Verwer

Boellaard

Veldt

2014

WJCO

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Core tip:This review provides an overview of the current applications of positron emission tomography for hypoxia and perfusion imaging in lung cancer. Available PET tracers are discussed and the benefits of combined hypoxia and perfusion PET imaging are clarified. Hypoxia imaging could aid in selecting patients for hypoxia-specific treatment strategies. To achieve this, consensus about the optimal imaging protocol and quantification method is essential. Large clinical trials are needed to confirm the value of hypoxia imaging for improving patient care.Verwer EE, Boellaard R, van der Veldt AAM. Positron emission tomography to assess hypoxia and perfusion in lung cancer.

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Section: F]fmisomentioning

confidence: 99%

Positron emission tomography to assess hypoxia and perfusion in lung cancer

Verwer

Boellaard

Veldt

2014

WJCO

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“…The purification of 64 Cu and the preparation of 64 Cu-ATSM were performed according to previously reported procedures [18], [27]. The radiochemical purity of the resulting 64 Cu-ATSM was greater than 95%, as determined by silica gel thin-layer chromatography (TLC; silica gel 60; Merck, Whitehouse Station, NJ, USA) with ethyl acetate as the mobile phase [28].…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, we recently reported that, in the Colon-26 tumor-bearing mouse model, 64 Cu-ATSM preferentially localized in intratumoral regions with high densities of CD133 + cells, which are designated as cancer stem cells or cancer stem cell-like cells. Additionally, 64 Cu-ATSM IRT inhibited tumor growth and killed not only CD133 − cancer cells, but also CD133 + cells [17], [18]. CD133 + cells are reportedly radiotherapy/chemotherapy resistant and possess a high metastatic potential [19], [20].…”

Section: Introductionmentioning

confidence: 99%

Controlled Administration of Penicillamine Reduces Radiation Exposure in Critical Organs during 64Cu-ATSM Internal Radiotherapy: A Novel Strategy for Liver Protection

Yoshii¹,

Matsumoto

Yoshimoto

et al. 2014

PLoS ONE

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Purpose 64Cu-diacetyl-bis (N 4-methylthiosemicarbazone) (64Cu-ATSM) is a promising theranostic agent that targets hypoxic regions in tumors related to malignant characteristics. Its diagnostic usefulness has been recognized in clinical studies. Internal radiotherapy (IRT) with 64Cu-ATSM is reportedly effective in preclinical studies; however, for clinical applications, improvements to reduce radiation exposure in non-target organs, particularly the liver, are required. We developed a strategy to reduce radiation doses to critical organs while preserving tumor radiation doses by controlled administration of copper chelator penicillamine during 64Cu-ATSM IRT.MethodsBiodistribution was evaluated in HT-29 tumor-bearing mice injected with 64Cu-ATSM (185 kBq) with or without oral penicillamine administration. The appropriate injection interval between 64Cu-ATSM and penicillamine was determined. Then, the optimal penicillamine administration schedule was selected from single (100, 300, and 500 mg/kg) and fractionated doses (100 mg/kg×3 at 1- or 2-h intervals from 1 h after 64Cu-ATSM injection). PET imaging was performed to confirm the effect of penicillamine with a therapeutic 64Cu-ATSM dose (37 MBq). Dosimetry analysis was performed to estimate human absorbed doses.ResultsPenicillamine reduced 64Cu accumulation in the liver and small intestine. Tumor uptake was not affected by penicillamine administration at 1 h after 64Cu-ATSM injection, when radioactivity was almost cleared from the blood and tumor uptake had plateaued. Of the single doses, 300 mg/kg was most effective. Fractionated administration at 2-h intervals further decreased liver accumulation at later time points. PET indicated that penicillamine acts similarly with the therapeutic 64Cu-ATSM dose. Dosimetry demonstrated that appropriately scheduled penicillamine administration reduced radiation doses to critical organs (liver, ovaries, and red marrow) below tolerance levels. Laxatives reduced radiation doses to the large intestine.ConclusionsWe developed a novel strategy to reduce radiation exposure in critical organs during 64Cu-ATSM IRT, thus promoting its clinical applications. This method could be beneficial for other 64Cu-labeled compounds.

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“…Lepin et al [110] developed a humanised anti-prostate stem cell antigen antibody fragment as an immuno-PET tracer tested pre-clinically in vivo, with a pilot clinical imaging study proposed. Yoshii et al [111] investigated the relationship between the accumulation of the PET tracer CuATSM, an agent which potentially images hypoxia, and the concentration of CD133þ cancer stem cells in a murine colon carcinoma model; ATSM was found to accumulate in CD133þ rich regions. This shows the potential for PET tracers to provide information regarding the tumour micro-environment that may be a surrogate for cancer stem cells.…”

Section: Cancer Stem Cellsmentioning

confidence: 99%