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); molecular imaging; positron emission tomography/computerized tomography (PET/CT); prostate cancer.

Figure 1

¹⁸F-FLT used for detection of prostate foci before and after chemotherapy. A weak response is seen, while the SUVmax value decreased from 3.6 to 2.3 in the left prostate lobe (circles in C and G). Upper row, baseline: from the left fusion image (A), computerized tomography (CT) image (B), fluorine-18 fluorothymidine with positron emission tomography (¹⁸F-FLT PET) image (C); and maximum intensity projection (MIP) image (D); lower row, after 4 weeks of therapy: from the left fusion image (E), CT image (F), ¹⁸F-FLT PET image (G), and MIP image (H). Color bar range from 0 to 5.

Figure 2

¹⁸F-FLT used for detection of retroperitoneal lymph node metastases before and after chemotherapy. A weak response was seen while the SUVmax value decreased from 4.1 to 2.1 in the left common iliac node (arrows in C and G). Upper row, baseline: from the left fusion image (A), CT image (B), ¹⁸F-FLT PET image (C), and MIP image (D); lower row, after 4 week therapy: from the left fusion image (E), CT image (F), ¹⁸F-FLT PET image (G), and MIP image (H). Color bar range from 0 to 5.

Figure 3

¹⁸F-FLT detection of prostate cancer metastases before and after therapy. The sclerotic skeletal metastases seen on CT are seen as defects on ¹⁸F-FLT, so the usefulness of ¹⁸F-FLT for detection of skeletal metastases is still unclear since visualization of lesions may be hindered by prominent background activity in the bone marrow. The skeletal metastases visualize most often as defects. Upper row, baseline: from the left fusion image (A), CT image (B), ¹⁸F-FLT PET image (C), and MIP image (D); lower row, after 4 week therapy: from the left fusion image (E), CT image (F), ¹⁸F-FLT PET image (G), and MIP image (H). Color bar range from 0 to 5.