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.

Molecular Imaging with 3′-deoxy-3′[(18)F]-Fluorothymidine (18F-FLT) PET/CT for Early Response to Targeted Therapies in Sarcomas: A Pilot Study

“…A baseline 18 F-FLT PET/CT was obtained before treatment with MDM2 or C-MET inhibitor followed by a second 18 F-FLT PET/CT approximately 1-15 weeks after treatment in all participants (Tables 1 and 2). The radiosynthesis of 18 F-FLT was produced according to a method already described [2][3][4]12]. Briefly, fluorine-18 fluoride was prepared by the 18 O (p, n) 18 F reaction using >95% O-18 enriched water as the target material with a titanium window and target holder.…”

“…Tumor proliferation and early response to molecularly targeted therapy can be imaged using 3 -deoxy-3 [(18)F]-fluorothymidine positron emission tomography (18 F-FLT PET/CT) [1][2][3][4][5].…”

Molecular imaging of metastatic atrial angiosarcoma with positron emission tomography (PET) tracer 3′-deoxy-3′[(18)F]-fluorothymidine, [(18)F]-FLT imaging and early response evaluation

“…Fluorine-18 fluorothymidine ( 18 F-FLT) is a structural analogue of thymidine, a DNA base. Interestingly, thymidine is not complexed into the DNA 11. It is captured in the cell by phosphorylation by thymidine kinase.…”

Possible Role of Ga-68 PSMA PET/CT in Evaluation of Systemic Treatment Response in Patients with Metastatic Prostate Cancer

“…Artmış uptake'inin DNA sentez hızı ve proliferatif indekslerle orantılı olduğu gösterilmiştir. Tedavi sonrası inflamatuvar değişikliklerden daha az etkilenmesi yanıt değerlendirmede avantaj olmakla birlikte PK'de kullanımı şu ana kadar genellikle preklinik çalışmalar şeklindedir (21). FLT PET'nin normal kemik iliğinde yoğun aktivitesi olması ve birçok ileri evre prostat kanserinde yaygın kemik metastazı olması nedeniyle tedavi yanıtını değerlendirme potansiyeli zor gibi görünmektedir.…”