title: Rapid dual-tracer PTSM+ATSM PET imaging of tumour blood flow and hypoxia: a simulation study.
abstract: Blood flow and hypoxia are interrelated aspects of physiology that affect cancer treatment and response. Cu-PTSM and Cu-ATSM are related PET tracers for blood flow and hypoxia, and the ability to rapidly image both tracers in a single scan would bring several advantages over conventional single-tracer techniques. Using dynamic imaging with staggered injections, overlapping signals for multiple PET tracers may be recovered utilizing information from kinetics and radioactive decay. In this work, rapid dual-tracer PTSM+ATSM PET was simulated and tested as a function of injection delay, order and relative dose for several copper isotopes, and the results were compared relative to separate single-tracer data. Time-activity curves representing a broad range of tumour blood flow and hypoxia levels were simulated, and parallel dual-tracer compartment modelling was used to recover the signals for each tracer. The main results were tested further using a torso phantom simulation of PET tumour imaging. Using scans as short as 30 minutes, the dual-tracer method provided measures of blood flow and hypoxia similar to single-tracer imaging. The best performance was obtained by injecting PTSM first and using a somewhat higher dose for ATSM. Comparable results for different copper isotopes suggest that tracer kinetics with staggered injections play a more important role than radioactive decay in the signal separation process. Rapid PTSM+ATSM PET has excellent potential for characterizing both tumour blood flow and hypoxia in a single, fast scan, provided that technological hurdles related to algorithm development and routine use can be overcome.
authors.affiliation: Utah Center for Advanced Imaging Research, Department of Radiology, University of Utah, Salt Lake City, UT 84108-1218, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Rust
authors.forename: D J
authors.initials: DJ
authors.lastname: Kadrmas
mesh_terms: D000465:Algorithms; D015687:Cell Hypoxia; D003198:Computer Simulation; D056831:Coordination Complexes; D006801:Humans; D000860:Hypoxia; D015233:Models, Statistical; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology*; D009942:Organometallic Compounds; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D012039:Regional Blood Flow; D012542:Scattering, Radiation; D013882:Thiosemicarbazones; D013997:Time Factors
chemical_list: D056831:Coordination Complexes; D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex