Dual-radiotracer translational SPECT neuroimaging. Comparison of three methods for the simultaneous brain imaging of D 2/3 and 5-HT 2A receptors.

Purpose: SPECT imaging with two radiotracers at the same time is feasible if two different radioisotopes are employed, given their distinct energy emission spectra. In the case of ¹²³ I and ¹²⁵ I, dual SPECT imaging is not straightforward: ¹²³ I emits photons at a principal energy emission spectrum of 143.1-179.9 keV. However, it also emits at a secondary energy spectrum (15-45 keV) that overlaps with the one of ¹²⁵ I and the resulting cross-talk of emissions impedes the accurate quantification of ¹²⁵ I. In this paper, we describe three different methods for the correction of this cross-talk and the simultaneous in vivo [ ¹²³ I]IBZM and [ ¹²⁵ I]R91150 imaging of D _2/3 and 5-HT _2A receptors in the rat brain.
Methods: Three methods were evaluated for the correction of the effect of cross-talk in a series of simultaneous, [ ¹²³ I]IBZM and [ ¹²⁵ I]R91150 in vivo and phantom SPECT scans. Method 1 employs a dual-energy window (DEW) approach, in which the cross-talk on ¹²⁵ I is considered a stable fraction of the energy emitted from ¹²³ I at the principal emission spectrum. The coefficient describing the relationship between the emission of ¹²³ I at the principal and the secondary spectrum was estimated from a series of single-radiotracer [ ¹²³ I]IBZM SPECT studies. In Method 2, spectral factor analysis (FA) is applied to separate the radioactivity from ¹²³ I and ¹²⁵ I on the basis of their distinct emission patterns across the energy spectrum. Method 3 uses a modified simplified reference tissue model (SRTM _C ) to describe the kinetics of [ ¹²⁵ I]R91150. It includes the coefficient describing the cross-talk on ¹²⁵ I from ¹²³ I in the model parameters. The results of the correction of cross-talk on [ ¹²⁵ I]R91150 binding potential (BP _ND ) with each of the three methods, using cerebellum as the reference region, were validated against the results of a series of single-radiotracer [ ¹²³ I]R91150 SPECT studies. In addition, the DEW approach (Method 1), considered to be the most straightforward to apply of the three, was further applied in a dual-radiotracer SPECT study of the relationship between D _2/3 and 5-HT _2A receptor binding in the striatum, both at the voxel and at the regional level.
Results: Average regional BP _ND values of [ ¹²⁵ I]R91150, estimated on the cross-talk corrected dual-radiotracer SPECT studies provided satisfactory correlations with the BP _ND values for [ ¹²³ I]R91150 from single-radiotracer studies: r = 0.92, p < 0.001 for Method 1, r = 0.92, p < 0.001 for Method 2, r = 0.92, p < 0.001, for Method 3. The coefficient describing the ratio of the ¹²³ I-emitted radioactivity at the ¹²⁵ I-emission spectrum to the radioactivity that it emits at its principal emission spectrum was 0.34 in vivo. Dual-radiotracer in vivo SPECT studies corrected with Method 1 demonstrated a positive correlation between D _2/3 and 5-HT _2A receptor binding in the rat nucleus accumbens at the voxel level. At the VOI-level, a positive correlation was confirmed in the same region (r = 0.78, p < 0.01).
Conclusion: Dual-radiotracer SPECT imaging using ¹²³ I and ¹²⁵ I-labeled radiotracers is feasible if the cross-talk of ¹²³ I on the ¹²⁵ I emission spectrum is properly corrected. The most straightforward approach is Method 1, in which a fraction (34%) of the radioactivity emitted from ¹²³ I at its principal energy spectrum is subtracted from the measured radioactivity at the spectrum of ¹²⁵ I. With this method, a positive correlation between the binding of [ ¹²³ I]IBZM and [ ¹²⁵ I]R91150 was demonstrated in the rat nucleus accumbens. This result highlights the interest of dual-radiotracer SPECT imaging to study multiple neurotransmitter systems at the same time and under the same biological conditions.
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