[(18)F]-FLT PET to predict early response to neoadjuvant therapy in KRAS wild-type rectal cancer: a pilot study

Ann Nucl Med. 2015 Jul;29(6):535-42. doi: 10.1007/s12149-015-0974-6. Epub 2015 Apr 22.

Abstract

Object: This pilot study evaluated the utility of 3'-deoxy-3'[18F]-fluorothymidine ([(18)F]-FLT) positron emission tomography (PET) to predict response to neoadjuvant therapy that included cetuximab in patients with wild-type KRAS rectal cancers.

Methods: Baseline [(18)F]-FLT PET was collected prior to treatment initiation. Follow-up [(18)F]-FLT was collected after three weekly infusions of cetuximab, and following a combined regimen of cetuximab, 5-FU, and radiation. Imaging-matched biopsies were collected with each PET study.

Results: Diminished [(18)F]-FLT PET was observed in 3/4 of patients following cetuximab treatment alone and in all patients following combination therapy. Reduced [(18)F]-FLT PET following combination therapy predicted disease-free status at surgery. Overall, [(18)F]-FLT PET agreed with Ki67 immunoreactivity from biopsy samples and surgically resected tissue, and was predictive of treatment-induced rise in p27 levels.

Conclusion: These results suggest that [(18)F]-FLT PET is a promising imaging biomarker to predict response to neoadjuvant therapy that included EGFR blockade with cetuximab in patients with rectal cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use
  • Cetuximab / therapeutic use
  • Chemoradiotherapy
  • Dideoxynucleosides*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multimodal Imaging / methods
  • Neoadjuvant Therapy
  • Pilot Projects
  • Positron-Emission Tomography* / methods
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Radiopharmaceuticals*
  • Rectal Neoplasms / diagnosis
  • Rectal Neoplasms / diagnostic imaging*
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / therapy*
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Dideoxynucleosides
  • KRAS protein, human
  • Radiopharmaceuticals
  • Proto-Oncogene Proteins p21(ras)
  • alovudine
  • Cetuximab