Evaluation of rapid dual-tracer⁶²Cu-PTSM +⁶²Cu-ATSM PET in dogs with spontaneously occurring tumors

Abstract

We are developing methods for imaging multiple PET tracers in a single scan with staggered injections, where imaging measures for each tracer are separated and recovered using differences in tracer kinetics and radioactive decay. In this work, signal-separation performance for rapid dual-tracer 62 Cu-PTSM (blood flow) + 62 Cu-ATSM (hypoxia) tumor imaging was evaluated in a large animal model. Four dogs with pre-existing tumors received a series of dynamic PET scans with 62 Cu-PTSM and 62 Cu-ATSM, permitting evaluation of a rapid dual-tracer protocol designed by previous simulation work. Several imaging measures were computed from the dual-tracer data and compared with those from separate, single-tracer imaging. Static imaging measures (e.g. SUV) for each tracer were accurately recovered from dual-tracer data. The wash-in (k 1 ) and washout (k 2 ) rate parameters for both tracers were likewise well recovered (r = 0.87 -0.99), but k 3 was not accurately recovered for PTSM (r = 0.19) and moderately well recovered for ATSM (r = 0.70). Some degree of bias was noted, however, which may potentially be overcome through further refinement of the signal-separation algorithms. This work demonstrates that complementary information regarding tumor blood flow and hypoxia can be acquired by a single dual-tracer PET scan, and also that the signal-separation procedure works effectively for real physiologic data with realistic levels of kinetic model-mismatch. Rapid multi-tracer PET has the potential to improve tumor assessment for image-guide therapy and monitoring, and further investigation with these and other tracers is warranted.

Simultaneous [99mTc]TRODAT-1 and [123I]ADAM Brain SPECT in Nonhuman Primates

“…Recently, one group has evaluated the usefulness of dual-tracer PET imaging in dogs with tumors using a staggered injection strategy. The imaging measures for each tracer are separated and recovered through the use of tracer kinetics and radioactive decay [35]. This approach is interesting and deserves further analysis and expansion for its possible use in neuroscience research.…”

Signal Separation and Parameter Estimation in Noninvasive Dual-Tracer PET Scans using Reference-Region Approaches

“…Kadrmas and Rust (2005) evaluated the possibility of a similar parallelmodel fitting approach in a simulation study for rapid dual-tracer scans. Various applications of rapid dual-tracer studies have been described recently, including simulation studies for measuring hypoxia and blood flow and tumor characterization using 62 Cu-PTSM (pyruvaldehydebis[N4-methylthiosemicarbazone]) and 62 Cu-ATSM (diacetyl-bis[N4-methylthiosemicarbazone]) in dogs (Black et al, 2008).…”

Simultaneous Dual-tracer PET Imaging of the Rat Brain and its Application in the Study of Cerebral Ischemia

“…Simultaneous imaging techniques alleviate the problems relating to image alignment and physiological changes inherent in successive imaging. Other sequential and simultaneous dual-tracer PET scans have been investigated [4][5][6][7][8][9], such as PET kinetic analysis with dual-tracer injection, where the aim of the work was to investigate the optimal injection intervals and administration dose ratios of the two tracers [6][7][8].…”