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
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  • Published online on: Friday, April 29, 2011
  • Pages: 91-100
  • DOI: 10.3892/ijo.2011.1019

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.
Journal Cover

July 2011
Volume 39 Issue 1

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

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Katz, S., Zhou, L., Ferrara, T., Wang, W., Mayes, P., Smith, C., & El-Deiry, W. (2011). FLT-PET may not be a reliable indicator of therapeutic response in p53-null malignancy. International Journal of Oncology, 39(1), 91-100.
MLA
Katz, Zhou, Ferrara, Wang, Mayes, Smith, and Wafik El-Deiry. "FLT-PET may not be a reliable indicator of therapeutic response in p53-null malignancy." International Journal of Oncology International Journal of Oncology 39.1 (2011): 91-100.
Chicago
Katz, Zhou, Ferrara, Wang, Mayes, Smith, and Wafik El-Deiry. "FLT-PET may not be a reliable indicator of therapeutic response in p53-null malignancy." International Journal of Oncology International Journal of Oncology 39 no. 1 (2011): 91-100.