FLT-PET may not be a reliable indicator of therapeutic response in p53-null malignancy

  • Authors:
    • Sharyn I. Katz
    • Lanlan Zhou
    • Thomas A. Ferrara
    • Wenge Wang
    • Patrick A. Mayes
    • Charles D. Smith
    • Wafik S. El-Deiry
  • View Affiliations

  • Published online on: April 29, 2011     https://doi.org/10.3892/ijo.2011.1019
  • Pages: 91-100
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Abstract

FDG (18F-deoxy-glucose) is the current gold standard for PET imaging. FLT (3'-deoxy-3'-(18F-fluorothymidine), a PET imaging marker of proliferation, has been proposed as an alternative to FDG for the assessment of therapeutic response. We examined the therapeutic predictive value of FLT-PET and FDG-PET using CALU-6, a human, p53-null, non-small cell lung cancer cell line with comparison of combined targeted therapy, TRAIL and sorafenib, versus combined conventional chemotherapy, docetaxel and cisplatin. CALU-6 tumor-bearing nu/nu mice (n=46) were evaluated in 3 therapeutic trials measuring FLT and FDG prediction of tumor response at 72 h following initiation of daily combination therapy with targeted agents, TRAIL (200 µg i.v.) and sorafenib (30 mg/kg i.p.) and compared to conventional chemotherapeutics cisplatin (3 mg/kg i.p.) and docetaxel (7.5 mg/kg i.p.). PET imaging response was compared to morphological and histological indicators of therapeutic response, including decreased vascu­larity (in vivo AngioSense imaging and anti-CD31 staining), slowed tumor growth (caliper measurements), decreased cellular proliferation (Ki-67 staining) and increased apoptosis (TUNEL staining). Decreases in tumor accumulation of FLT (FLTMAX -30%, p=0.03) at 72 h post treatment were observed in response to TRAIL and sorafenib combination therapy resulting in smaller, less vascular, more apoptotic tumors. No similar reduction in tumor accumulation of FLT (FLTMAX -2%, p=0.67) was observed 72 h following initiation of cisplatin and docetaxel combination therapy, despite histological and morphological evidence of drug response. In contrast, tumor imaging with FDG did demonstrate a decrease in accumulation in both treatment groups, -21% (p=0.30) in response to cisplatin/docetaxel and -8% (p=0.59) in response to TRAIL/sorafenib, but did not reach statistical significance. FLT, but not FDG, is predictive of therapeutic response to the targeted regimen TRAIL/sorafenib. However, FLT-PET may not predict thera­peutic response to DNA damaging agents in p53-null tumors, likely due to loss of cell cycle control of thymidine kinase 1 (TK1). Thus, tumor imaging response by FLT may be limited in human tumors without functional p53.

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July 2011
Volume 39 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Katz SI, Zhou L, Ferrara TA, Wang W, Mayes PA, Smith CD and El-Deiry WS: FLT-PET may not be a reliable indicator of therapeutic response in p53-null malignancy. Int J Oncol 39: 91-100, 2011.
APA
Katz, S.I., Zhou, L., Ferrara, T.A., Wang, W., Mayes, P.A., Smith, C.D., & El-Deiry, W.S. (2011). FLT-PET may not be a reliable indicator of therapeutic response in p53-null malignancy. International Journal of Oncology, 39, 91-100. https://doi.org/10.3892/ijo.2011.1019
MLA
Katz, S. I., Zhou, L., Ferrara, T. A., Wang, W., Mayes, P. A., Smith, C. D., El-Deiry, W. S."FLT-PET may not be a reliable indicator of therapeutic response in p53-null malignancy". International Journal of Oncology 39.1 (2011): 91-100.
Chicago
Katz, S. I., Zhou, L., Ferrara, T. A., Wang, W., Mayes, P. A., Smith, C. D., El-Deiry, W. S."FLT-PET may not be a reliable indicator of therapeutic response in p53-null malignancy". International Journal of Oncology 39, no. 1 (2011): 91-100. https://doi.org/10.3892/ijo.2011.1019