Combined injection of 18F-fluorodeoxyglucose and 3′-Deoxy-3′-[18F]fluorothymidine PET achieves more complete identification of viable lung cancer cells in mice and patients than individual radiopharmaceutical: A proof-of-concept study

Xiao Feng Li, Tao Huang, Huijie Jiang, Xuemei Wang, Baozhong Shen, Xiangcheng Wang, Chin K. Ng, Gregory C. Postel, Ali Civelek

Research output: Contribution to journalArticle

Abstract

Purpose: The objective is to validate the combination of 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) and 18F-fluorodeoxyglucose (18F-FDG) as a "novel" positron emission tomography (PET) tracer for better visualization of cancer cell components in solid cancers than individual radiopharmaceutical. Methods: Nude mice with subcutaneous xenografts of human non-small cell lung cancer A549 and HTB177 cells and patients with lung cancer were included. In ex vivo study, intratumoral radioactivity of 18F-FDG, 18F-FLT, and the cocktail of 18F-FDG and 18F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, 18F-FDG PET and 18F-FLT PET were conducted in the same subjects (mice and patients) 10 to 14 hours apart. Second, PET scan was also performed 1 hour after one tracer injection; subsequently, the other was administered and followed the second PET scan in the mouse. Finally, 18F-FDG and 18F-FLT cocktail PET scan was also performed in the mouse. Results:When injected individually, 18F-FDG highly accumulated in hypoxic zones and high 18F-FLT in proliferative cancer cells. In case of cocktail injection, high radioactivity correlatedwith hypoxic regions and highly proliferative and normoxic regions. PET detected that intratumoral distribution of 18F-FDG and 18F-FLT was generally mismatched in both rodents and patients. Combination of 18F-FLT and 18F-FDG appeared to map more cancer tissue than single-tracer PET. Conclusions: Combination of 18F-FDG and 18F-FLT PET imaging would give a more accurate representation of total viable tumor tissue than either tracer alone and would be a powerful imaging strategy for cancer management.

Original languageEnglish (US)
Pages (from-to)775-783
Number of pages9
JournalTranslational Oncology
Volume6
Issue number6
DOIs
StatePublished - Dec 2013
Externally publishedYes

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Radiopharmaceuticals
Fluorodeoxyglucose F18
Positron-Emission Tomography
Lung Neoplasms
Injections
Neoplasms
Radioactivity
alovudine
Bromodeoxyuridine
Cellular Structures
Autoradiography
Heterografts
Nude Mice
Non-Small Cell Lung Carcinoma
Rodentia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Combined injection of 18F-fluorodeoxyglucose and 3′-Deoxy-3′-[18F]fluorothymidine PET achieves more complete identification of viable lung cancer cells in mice and patients than individual radiopharmaceutical : A proof-of-concept study. / Li, Xiao Feng; Huang, Tao; Jiang, Huijie; Wang, Xuemei; Shen, Baozhong; Wang, Xiangcheng; Ng, Chin K.; Postel, Gregory C.; Civelek, Ali.

In: Translational Oncology, Vol. 6, No. 6, 12.2013, p. 775-783.

Research output: Contribution to journalArticle

Li, Xiao Feng ; Huang, Tao ; Jiang, Huijie ; Wang, Xuemei ; Shen, Baozhong ; Wang, Xiangcheng ; Ng, Chin K. ; Postel, Gregory C. ; Civelek, Ali. / Combined injection of 18F-fluorodeoxyglucose and 3′-Deoxy-3′-[18F]fluorothymidine PET achieves more complete identification of viable lung cancer cells in mice and patients than individual radiopharmaceutical : A proof-of-concept study. In: Translational Oncology. 2013 ; Vol. 6, No. 6. pp. 775-783.
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abstract = "Purpose: The objective is to validate the combination of 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) and 18F-fluorodeoxyglucose (18F-FDG) as a {"}novel{"} positron emission tomography (PET) tracer for better visualization of cancer cell components in solid cancers than individual radiopharmaceutical. Methods: Nude mice with subcutaneous xenografts of human non-small cell lung cancer A549 and HTB177 cells and patients with lung cancer were included. In ex vivo study, intratumoral radioactivity of 18F-FDG, 18F-FLT, and the cocktail of 18F-FDG and 18F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, 18F-FDG PET and 18F-FLT PET were conducted in the same subjects (mice and patients) 10 to 14 hours apart. Second, PET scan was also performed 1 hour after one tracer injection; subsequently, the other was administered and followed the second PET scan in the mouse. Finally, 18F-FDG and 18F-FLT cocktail PET scan was also performed in the mouse. Results:When injected individually, 18F-FDG highly accumulated in hypoxic zones and high 18F-FLT in proliferative cancer cells. In case of cocktail injection, high radioactivity correlatedwith hypoxic regions and highly proliferative and normoxic regions. PET detected that intratumoral distribution of 18F-FDG and 18F-FLT was generally mismatched in both rodents and patients. Combination of 18F-FLT and 18F-FDG appeared to map more cancer tissue than single-tracer PET. Conclusions: Combination of 18F-FDG and 18F-FLT PET imaging would give a more accurate representation of total viable tumor tissue than either tracer alone and would be a powerful imaging strategy for cancer management.",
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TY - JOUR

T1 - Combined injection of 18F-fluorodeoxyglucose and 3′-Deoxy-3′-[18F]fluorothymidine PET achieves more complete identification of viable lung cancer cells in mice and patients than individual radiopharmaceutical

T2 - A proof-of-concept study

AU - Li, Xiao Feng

AU - Huang, Tao

AU - Jiang, Huijie

AU - Wang, Xuemei

AU - Shen, Baozhong

AU - Wang, Xiangcheng

AU - Ng, Chin K.

AU - Postel, Gregory C.

AU - Civelek, Ali

PY - 2013/12

Y1 - 2013/12

N2 - Purpose: The objective is to validate the combination of 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) and 18F-fluorodeoxyglucose (18F-FDG) as a "novel" positron emission tomography (PET) tracer for better visualization of cancer cell components in solid cancers than individual radiopharmaceutical. Methods: Nude mice with subcutaneous xenografts of human non-small cell lung cancer A549 and HTB177 cells and patients with lung cancer were included. In ex vivo study, intratumoral radioactivity of 18F-FDG, 18F-FLT, and the cocktail of 18F-FDG and 18F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, 18F-FDG PET and 18F-FLT PET were conducted in the same subjects (mice and patients) 10 to 14 hours apart. Second, PET scan was also performed 1 hour after one tracer injection; subsequently, the other was administered and followed the second PET scan in the mouse. Finally, 18F-FDG and 18F-FLT cocktail PET scan was also performed in the mouse. Results:When injected individually, 18F-FDG highly accumulated in hypoxic zones and high 18F-FLT in proliferative cancer cells. In case of cocktail injection, high radioactivity correlatedwith hypoxic regions and highly proliferative and normoxic regions. PET detected that intratumoral distribution of 18F-FDG and 18F-FLT was generally mismatched in both rodents and patients. Combination of 18F-FLT and 18F-FDG appeared to map more cancer tissue than single-tracer PET. Conclusions: Combination of 18F-FDG and 18F-FLT PET imaging would give a more accurate representation of total viable tumor tissue than either tracer alone and would be a powerful imaging strategy for cancer management.

AB - Purpose: The objective is to validate the combination of 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) and 18F-fluorodeoxyglucose (18F-FDG) as a "novel" positron emission tomography (PET) tracer for better visualization of cancer cell components in solid cancers than individual radiopharmaceutical. Methods: Nude mice with subcutaneous xenografts of human non-small cell lung cancer A549 and HTB177 cells and patients with lung cancer were included. In ex vivo study, intratumoral radioactivity of 18F-FDG, 18F-FLT, and the cocktail of 18F-FDG and 18F-FLT detected by autoradiography was compared with hypoxia (by pimonidazole) and proliferation (by bromodeoxyuridine) in tumor section. In in vivo study, first, 18F-FDG PET and 18F-FLT PET were conducted in the same subjects (mice and patients) 10 to 14 hours apart. Second, PET scan was also performed 1 hour after one tracer injection; subsequently, the other was administered and followed the second PET scan in the mouse. Finally, 18F-FDG and 18F-FLT cocktail PET scan was also performed in the mouse. Results:When injected individually, 18F-FDG highly accumulated in hypoxic zones and high 18F-FLT in proliferative cancer cells. In case of cocktail injection, high radioactivity correlatedwith hypoxic regions and highly proliferative and normoxic regions. PET detected that intratumoral distribution of 18F-FDG and 18F-FLT was generally mismatched in both rodents and patients. Combination of 18F-FLT and 18F-FDG appeared to map more cancer tissue than single-tracer PET. Conclusions: Combination of 18F-FDG and 18F-FLT PET imaging would give a more accurate representation of total viable tumor tissue than either tracer alone and would be a powerful imaging strategy for cancer management.

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