Metabolomics of In-111 using coincidence imaging

1874 Objectives The decay of In-111 results in the successive emission of two photons with an anisotropic angular distribution. The associated intermediate state half-life of 85 ns is long enough to allow the Cd-111 progeny nucleus to be affected by external electric and magnetic fields, resulting in a perturbation of this angular anisotropy. The perturbed angular correlation has been previously studied to assess in vivo metabolism of several In-111 tracers [1]. However, the concept of imaging these signature perturbations in conjunction with standard gamma camera imaging has not been explored. The measurement of coincident gamma rays can be leveraged to evaluate the anisotropy perturbation over time and can be used to assess indium-based radiopharmaceutical binding affinity and metabolic changes. Our primary objective is to identify using simulation the gamma camera imaging conditions (timing window resolution and activity) under which the anisotropy perturbations of In-111-based radiopharmaceuticals (In-111-DTPA and chloride) may be measured. Methods GEANT4 was used to simulate the decay of the In-111 nucleus and to transport the emissions through a model of a Siemens Symbia type “S” gamma camera with a 5/8-inch thick crystal and medium energy collimators. The anisotropy of 3 forms of In-111 (unperturbed, DTPA, and chloride) was also modeled using known time-integrated attenuation factors [2, 3]. In each case, the expected emission angular distribution from the 3 forms of In-111 is sampled via a standard rejection technique and each detected gamma ray emission is assigned a timestamp. Candidate coincident events are defined as a single 171 keV gamma-ray followed by a single 245 keV gamma-ray within a specified time window. For each of the In-111 forms, we calculate the angular anisotropy while varying the gamma camera timing window from 100 microseconds to 100 ns and increasing the number of coincident events to represent a wide range of activity. For each simulated time resolution and activity, we record the number of true and random coincident events that are detected within a preset time interval and repeat this experiment for 1000 realizations. In each experiment, the angular anisotropy is computed as (N180 - N90)/N90, where N180 and N90 are the measured coincident counts with 180 and 90 degree dual-headed gamma camera configurations, respectively. These anisotropies were then plotted for different combinations of timing window and activity to determine the parameter set that can differentiate between the various forms of In-111. Results As expected increasing the timing window increases the total number of observed coincidences albeit at the expense of true coincidences. The number of true coincidences peaked at a timing resolution of 500 ns independent of external background and form of In-111. Furthermore, increasing the amount of activity increases the ability to identify the anisotropy perturbations of In-111 tracers. The results from the simulated anisotropy experiments showed that with a 500 ns time resolution and 5,000 coincident events, In-111 chloride could be distinguished from In-111-DTPA. Conclusions This work demonstrates that In-111 emission anisotropy using coincident events measured with a gamma camera could be used to differential different forms of In-111-based radiopharmaceuticals. Further work to translate this simulation study to realistic clinical imaging conditions is ongoing. REFERENCES: 1) D. A. Goodwin, C. F. Meares, and C. H. Song, “The study of In-111-labeled compounds in mice, using perturbed angular correlations of gamma radiations”, Radiology 105, p. 699-702, (1972). 2) R. M. Steffen, “Influence of the time-dependent quadrupole interaction on the directional correlation of the Cd-111 gamma rays”, Phys. Rev.103 (1), p. 116-125 (1956). 3) P. C. Hargrave, F. A. Smith, K. Brown, et. al., “Time-differential PAC parameters for In-111-DTPA labeled vesicles”, Chem. Phys. Lett.246, p. 626-631, (1995).