An Assessment of Early Response to Targeted Therapy via Molecular Imaging: A Pilot Study of 3′-deoxy-3′[(18)F]-Fluorothymidine Positron Emission Tomography 18F-FLT PET/CT in Prostate Adenocarcinoma

Abstract

Fluorothymidine is a thymidine analog labeled with fluorine-18 fluorothymidine for positron emission tomography (18F-FLT-PET) imaging. Thymidine is a nucleic acid that is used to build DNA. Fluorine-18 fluorothymidine (18F-FLT) utilizes the same metabolic pathway as does thymidine but has a very low incidence of being incorporated into the DNA (<1%). 18F-FLT-PET could have a role in the evaluation of response to targeted therapy. We present here a pilot study where we investigated cellular metabolism and proliferation in patients with prostate cancer before and after targeted therapy. Seven patients with Stage IV prostate adenocarcinoma, candidates for targeted therapy inhibiting the hepatocyte growth factor/tyrosine-protein kinase Met (HGF/C-MET) pathway, were included in this study. The HGF/C-MET pathway is implicated in prostate cancer progression, and an evaluation of the inhibition of this pathway could be valuable. 18F-FLT was performed at baseline and within four weeks post-therapy. Tumor response was assessed semi-quantitatively and using visual response criteria. The range of SUVmax for 18F-FLT at baseline in the prostate varied from 2.5 to 4.2. This study demonstrated that 18F-FLT with positron emission tomography/computerized tomography (18F-FLT PET/CT) had only limited applications in the early response evaluation of prostate cancer. 18F-FLT PET/CT may have some utility in the assessment of response in lymph node disease. However, 18F-FLT PET/CT was not found to be useful in the evaluation of the prostate bed, metastatic skeletal disease, and liver disease.

Keywords

• fluorine-18 fluorothymidine (18F-FLT)
• prostate cancer
• positron emission tomography/computerized tomography (PET/CT)
• molecular imaging