[99mTc]Tc-duramycin, a potential molecular probe for early prediction of tumor response after chemotherapy

Li, Yang; Liu, Cheng; Xu, Xiaoping; Lü, Xiaoling; Luo, Jia; Gray, Brian; Pak, Koon Y.; Cheng, Jingyi; Zhang, Yingjian

doi:10.1016/j.nucmedbio.2018.07.003

Cited by 14 publications

(9 citation statements)

References 41 publications

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“…Their observation that a negative imaging outcome does not consequently predict a negative response to the therapy is in line with the results obtained in our study and further sustains our hypothesis that the reliability of Annexin V-based apoptosis imaging can be impaired if the therapy significantly affects the tumor vasculature, leading to a reduced delivery of the probe to the tumor. For further investigations, it would be interesting to include small molecule imaging probes that detect apoptosis, e.g., analogues of duramycin [ 35 , 36 ], and to compare apoptosis imaging using small molecule and Annexin V-based probes with glucose metabolism measurements for monitoring the response to different anti-cancer therapies.…”

Section: Discussionmentioning

confidence: 99%

Change of Apoptosis and Glucose Metabolism in Lung Cancer Xenografts during Cytotoxic and Anti-Angiogenic Therapy Assessed by Annexin V Based Optical Imaging and 18F-FDG-PET/CT

Groß

Palmowski

Doleschel

et al. 2021

Contrast Media & Molecular Imaging

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Aim of the Study. To compare Annexin V-based optical apoptosis imaging with the assessment of the glucose metabolism using 18F-FDG-PET/CT for monitoring the response to cytotoxic (carboplatin) and anti-angiogenic (sunitinib) therapy. Methods. For apoptosis imaging, the near-infrared probe Annexin Vivo750 was used in combination with fluorescence molecular tomography and microcomputed tomography (FMT/µCT). Glucose metabolism was assessed using 18F-FDG-PET/CT. Five groups of nude mice bearing lung cancer xenografts (A549) were investigated: (i) untreated controls and two groups after (ii) cytotoxic (carboplatin) or (iii) anti-angiogenic (sunitinib) treatment for four and nine days, respectively. Imaging data were validated by immunohistochemistry. Results. In response to carboplatin treatment, an inverse relation was found between the change in glucose metabolism and apoptosis in A549 tumors. Annexin Vivo showed a continually increasing tumor accumulation, while the tumor-to-muscle ratio of 18F-FDG continuously decreased during therapy. Immunohistochemistry revealed a significantly higher tumor apoptosis ( p = 0.007 ) and a minor but not significant reduction in vessel density only at day 9 of carboplatin therapy. Interestingly, during anti-angiogenic treatment there was an early drop in the tumor-to-muscle ratio between days 0 and 4, followed by a subsequent minor decrease (18F-FDG tumor-to-muscle-ratio: 1.9 ± 0.4; day 4: 1.1 ± 0.2; day 9: 1.0 ± 0.2; p = 0.021 and p = 0.001 , respectively). The accumulation of Annexin Vivo continuously increased over time (Annexin Vivo: untreated: 53.7 ± 36.4 nM; day 4: 87.2 ± 53.4 nM; day 9: 115.1 ± 103.7 nM) but failed to display the very prominent early induction of tumor apoptosis that was found by histology already at day 4 (TUNEL: p = 0.0036 ) together with a decline in vessel density (CD31: p = 0.004 ), followed by no significant changes thereafter. Conclusion. Both molecular imaging approaches enable visualizing the effects of cytotoxic and anti-angiogenic therapy in A549 tumors. However, the early and strong tumor apoptosis induced by the anti-angiogenic agent sunitinib was more sensitively and reliably captured by monitoring of the glucose metabolism as compared to Annexin V-based apoptosis imaging.

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Section: Discussionmentioning

confidence: 99%

Change of Apoptosis and Glucose Metabolism in Lung Cancer Xenografts during Cytotoxic and Anti-Angiogenic Therapy Assessed by Annexin V Based Optical Imaging and 18F-FDG-PET/CT

Groß

Palmowski

Doleschel

et al. 2021

Contrast Media & Molecular Imaging

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“…Apoptosis was also known to participate in the classical pathological processes of cardiovascular disease. Using radionuclide imaging of apoptosis, abundant preclinical trials have been performed in the assessment of atherosclerotic plaques [57,58], aortic aneurysm (AA) [59], ischemia-reperfusion injury [60], and their therapy effectiveness [61][62][63][64]. Some of them have been conducted in humans and obtained positive results.…”

Section: Apoptosis Imaging In Cardiovascular Diseasementioning

confidence: 99%

Radionuclide imaging of apoptosis for clinical application

Qin

Jiang

Liu

et al. 2021

Eur J Nucl Med Mol Imaging

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Apoptosis was a natural, non-inflammatory, energy-dependent form of programmed cell death (PCD) that can be discovered in a variety of physiological and pathological processes. Based on its characteristic biochemical changes, a great number of apoptosis probes for single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have been developed. Radionuclide imaging with these tracers were potential for the repetitive and selective detection of apoptotic cell death in vivo, without the need for invasive biopsy. In this review, we overviewed molecular mechanism and specific biochemical changes in apoptotic cells and summarized the existing tracers that have been used in clinical trials as well as their potentialities and limitations. Particularly, we highlighted the clinic applications of apoptosis imaging as diagnostic markers, early-response indicators, and prognostic predictors in multiple disease fields.

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“…6 More recently, Li et al showed that 99m Tc-duramycin exhibited significantly higher uptake in cisplatin-treated tumors than in untreated tumors and also higher tumor uptake after 3 days of cisplatin treatment than before treatment in a mouse model of human breast cancer. 144 Nevertheless, tumor size reduction could not be observed until the eighth day after treatment, which was much later than what could be achieved by 99m Tc-duramycin imaging. 144 Moreover, the influence of kit formulation, purification, and species difference on pharmacokinetic and targeting characteristics of 99m Tc-duramycin was explored, aiming to identify the most favorable condition for further use.…”

Section: ■ Apoptosis Imagingmentioning

confidence: 99%

Imaging Cell Death: Focus on Early Evaluation of Tumor Response to Therapy

et al. 2020

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Cell death plays a prominent role in the treatment of cancer, because most anticancer therapies act by the induction of cell death including apoptosis, necrosis, and other pathways of cell death. Imaging cell death helps to identify treatment responders from nonresponders and thus enables patient-tailored therapy, which will increase the likelihood of treatment response and ultimately lead to improved patient survival. By taking advantage of molecular probes that specifically target the biomarkers/biochemical processes of cell death, cell death imaging can be successfully achieved. In recent years, with the increased understanding of the molecular mechanism of cell death, a variety of well-defined biomarkers/biochemical processes of cell death have been identified. By targeting these established cell death biomarkers/biochemical processes, a set of molecular imaging probes have been developed and evaluated for early monitoring treatment response in tumors. In this review, we mainly present the recent advances in identifying useful biomarkers/biochemical processes for both apoptosis and necrosis imaging and in developing molecular imaging probes targeting these biomarkers/biochemical processes, with a focus on their application in early evaluation of tumor response to therapy.

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[99mTc]Tc-duramycin, a potential molecular probe for early prediction of tumor response after chemotherapy

Cited by 14 publications

References 41 publications

Change of Apoptosis and Glucose Metabolism in Lung Cancer Xenografts during Cytotoxic and Anti-Angiogenic Therapy Assessed by Annexin V Based Optical Imaging and 18F-FDG-PET/CT

Change of Apoptosis and Glucose Metabolism in Lung Cancer Xenografts during Cytotoxic and Anti-Angiogenic Therapy Assessed by Annexin V Based Optical Imaging and 18F-FDG-PET/CT

Radionuclide imaging of apoptosis for clinical application

Imaging Cell Death: Focus on Early Evaluation of Tumor Response to Therapy

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