Optimization of technetium-99m Sestamibi single-photon emission tomography to define multidrug resistance with confidence

BACKGROUND: The efflux rate of technetium-99m Sestamibi (99mTc-Sestamibi) is a kinetic phenomenon related to the response of cancer cells to chemotherapy, and may be used to determine drug resistance. Measurement of the efflux rate requires accurate quantitative single-photon emission tomography (SPET) imaging within the time constraints imposed by the kinetics of the process. METHODS: A phantom study, at activity concentrations typically found with 99mTc-Sestamibi in vivo, was undertaken to optimize the SPET parameters and, in particular, to determine whether 180 degrees acquisition arcs with heads in 'L' configuration could be used for accurate quantification. Following the development of the most appropriate SPET protocol, a small patient pilot study was undertaken. RESULTS: Studies designed to evaluate statistical uncertainty (noise), contrast restitution and spatial resolution of the data sets, using different acquisition and reconstruction parameters, showed that 180 degrees SPET using a 64 x 64 matrix, 6 degrees angular sampling and iterative reconstruction was optimal. Finer linear and/or angular sampling afforded negligible improvement in resolution, but markedly increased the statistical uncertainty. Comparison of 360 degrees and 180 degrees acquisitions, utilizing conventional filtered backprojection and iterative reconstruction algorithms, demonstrated that the statistical uncertainty was reduced to a greater extent for 180 degrees data collection. For 360 degrees (64 x 64) data acquisition, statistical uncertainty decreased from 15% to 11% using the iterative algorithm, whilst the 180 degrees (64 x 64) data showed a reduction from 20% to 7%, and approached values obtained by planar imaging. The efflux measurements obtained in the patient pilot study were consistent with the observed chemotherapy response. CONCLUSION: Our study shows that 180 degrees acquisition arcs are a practical option for accurate quantitative SPET kinetic imaging for potential studies of chemotherapy response in patients with lung cancer.