FLT showing promise for head and neck cancer response

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Tumor cell proliferation and repopulation contribute to resistance to chemoradiotherapy in head and neck cancer. The PET tracer 3'-deoxy-3'-(18)F-fluorothymidine ([18]F-FLT) can image tumor cell proliferation before and during radiotherapy, and it may provide biologic tumor information useful in chemoradiotherapy planning, according to research conducted at the University of Iowa Hospitals and Clinics and published in the July issue of the Journal of Nuclear Medicine.

Scientists at the facility investigated the kinetic behavior of18F-FLT before and early after initiation of chemoradiation therapy in patients with squamous cell head and neck cancer.

They chose to conduct a kinetic analysis to determine if that process, compared with standardized uptake values (SUVs), showed stronger correlation with cellular proliferation markers or only provided similar information.

“Our data show that initially during chemoradiation therapy the phosphorylation rate of 18F-FLT in tumors is significantly decreased, whereas the other parameters are not significantly changed from baseline,” the authors wrote.

Pretherapy (left) and midtherapy (right) 18F-FLT PET images of patient with right tonsillar neoplasm (arrowhead), with bilateral cervical nodal metastases (solid arrows). Note interval decrease in 18F-FLT uptake in tumor and marked reduction in cervical bone marrow activity (dashed arrow). Image and caption courtesy of SNM.

Seven patients with histologically proven squamous cell head and neck cancer underwent two 18F-FLT PET scans: one before the initiation of therapy and one after five daily fractions of radiotherapy. Six of the seven patients in the cohort also had one cycle of concurrent chemotherapy prior to the post-radiotherapy PET scan.

All imaging was performed on an ECAT EXACT HR+ PET system (Siemens Healthcare) in 3D mode. Dynamic image data for the primary tumors and cervical nodes were fit to a two-compartment model using the PMOD Kinetic Modeling Tool (PMOD Technologies), and the kinetic behavior of the 18F-FLT was calculated. SUV was also calculated for each patient’s primary tumor as well as their 18F-FLT-avid cervical lymph nodes for all scans.

The scientists noted that compartmental analysis of 18F-FLT provides important information on the rate of initial passive diffusion, efflux, phosphorylation, and of 18F-FLT in the tumor.

Concurrent with imaging, venous and arterial blood sampling was performed and whole blood and plasma were assayed for total radioactivity. In addition, venous samples were assayed for unchanged 18F-FLT and metabolites. The fraction of unchanged 18F-FLT versus time in the venous samples was fit to a single exponential curve, which was used to correct the arterial plasma values for the presence of metabolites.

“Results of this study show that SUV (mean and maximum) obtained at 45–60 minutes after the initiation of 18F-FLT infusion shows excellent correlation with parameters obtained through rigorous quantitative modeling for 18F-FLT uptake in squamous cell head and neck tumors,” the authors wrote. “Significant change in 18F-FLT uptake was observed in cancer tissue after one week of chemoradiotherapy. These differences are most consistent with decreases in thymidine kinase activity in tumor tissue after therapy.”

The researchers noted that imaging requirements for compartmental analysis are relatively complex for routine clinical use, requiring dynamic imaging, multiple arterial and venous blood samples, and expertise in pharmacokinetics analysis. Their investigation demonstrated that SUV calculations provide information nearly equivalent to that provided by these more complex parameters.