Abstract
Fluorine-18-2-deoxy-2-lluoro-d-glucose (18F-FDG) is a useful positron emission tomography (PET) probe for differentiating tumors from benign lesions and for evaluating therapeutic effects. However, limitations of FDG-PET have recently been noted and the development of post-FDG molecular probes is strongly required. Here, we describe our basic studies on post-FDG molecular probes for the assessment of tumor malignancy and response to therapy, focusing on cell proliferation and apoptosis.
We evaluated the usefulness of FDG, 3′-deoxy-3′-18F-fluorothymidine (FLT; a thymidine analog), and l-11C-melhionine (MET) for differentiating tumors (hepatomas) from granulomas in experimental rat models. FDG and FLT levels in the granulomas were comparable to those in the hepatomas. MET uptake in the granulomas was significantly lower than that in the tumors. These results were further confirmed by animal PET studies. Thus, MET could have a potential value in accurately differentiating malignant tumors from benign lesions. Next, we compared the potentials of FDG and FLT for assessing response to molecular-targeting therapy with a tyrosine kinase inhibitor, gefitinib. Two days after the treatment, FLT uptake levels in the tumor were significantly reduced, but those of FDG were not. Ki-67 expression and phosphorylated epidermal growth factor receptor (P-EGFR) in the tumor were suppressed after gelilinib therapy, while there was no definite change in the expression levels of EGFR. In addition, there was no statistically significant change in the tumor size in comparisons of before and after the treatment in any groups. Accordingly, FLT can detect the antiproliferative effects of molecular-targeting therapy with gefitinib early, before there are significant changes in tumor size.
The relationship between apoptosis and glucose utilization was determined after chemotherapy using 99mTc-annexin A5 (an apoptosis marker) and FDG. The rats bearing hepatomas were divided into three groups: cyclophosphamide (150 mg/kg, i.p.), gemcitabine (90 mg/kg, i.v.), and control. After the chemolherapy, 99mTc-annexin A5 uptake in the tumor was significanlly increased, while FDG uplake was significantly decreased. The rate of terminal deoxynucleolidyl transferase-medialed deoxyuridine triphosphate nick-end labeling (TUNEL)-positively stained cells was significantly increased in both treatment groups. Thus, the increase in 99mTc-annexin A5 uptake as well as the decrease in FDG uptake in tumors could be useful markers for predicting therapeutic outcomes of chemotherapy.
These results indicate the potential value of molecular probes for cell proliferation and apoptosis in the assessment of tumor malignancy and response to therapy. A multiprobe approach could solve the problems wilh FDG-PET and open a new era of personalized medicine.
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Kuge, Y., Zhao, S., Takei, T., Tamaki, N. (2010). Molecular Imaging for the Assessment of Tumor Malignancy and Response to Therapy. In: Tamaki, N., Kuge, Y. (eds) Molecular Imaging for Integrated Medical Therapy and Drug Development. Springer, Tokyo. https://doi.org/10.1007/978-4-431-98074-2_3
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DOI: https://doi.org/10.1007/978-4-431-98074-2_3
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