Dual-radiotracer translational SPECT neuroimaging. Comparison of three methods for the simultaneous brain imaging of D and 5-HT 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 I and I, dual SPECT imaging is not straightforward: 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 I and the resulting cross-talk of emissions impedes the accurate quantification of I. In this paper, we describe three different methods for the correction of this cross-talk and the simultaneous in vivo [I]IBZM and [I]R91150 imaging of D and 5-HT receptors in the rat brain.

Methods: Three methods were evaluated for the correction of the effect of cross-talk in a series of simultaneous, [I]IBZM and [I]R91150 in vivo and phantom SPECT scans. Method 1 employs a dual-energy window (DEW) approach, in which the cross-talk on I is considered a stable fraction of the energy emitted from I at the principal emission spectrum. The coefficient describing the relationship between the emission of I at the principal and the secondary spectrum was estimated from a series of single-radiotracer [I]IBZM SPECT studies. In Method 2, spectral factor analysis (FA) is applied to separate the radioactivity from I and I on the basis of their distinct emission patterns across the energy spectrum. Method 3 uses a modified simplified reference tissue model (SRTM) to describe the kinetics of [I]R91150. It includes the coefficient describing the cross-talk on I from I in the model parameters. The results of the correction of cross-talk on [I]R91150 binding potential (BP) with each of the three methods, using cerebellum as the reference region, were validated against the results of a series of single-radiotracer [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 and 5-HT receptor binding in the striatum, both at the voxel and at the regional level.

Results: Average regional BP values of [I]R91150, estimated on the cross-talk corrected dual-radiotracer SPECT studies provided satisfactory correlations with the BP values for [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 I-emitted radioactivity at the 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 and 5-HT 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 I and I-labeled radiotracers is feasible if the cross-talk of I on the I emission spectrum is properly corrected. The most straightforward approach is Method 1, in which a fraction (34%) of the radioactivity emitted from I at its principal energy spectrum is subtracted from the measured radioactivity at the spectrum of I. With this method, a positive correlation between the binding of [I]IBZM and [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.