Objective: DAT^IQ has been developed as a novel analytical approach to improve the sensitivity and statistical efficiency of dopamine transporter (DaT) SPECT quantification over previously available specific binding ratio (SBR) approaches. In this study, DAT^IQ was applied to data from SURE-PD3, a phase 3, double-blind, placebo-controlled trial [1] and compared to previous SBR analysis.

Background: DaT SPECT imaging, using [123I]Ioflupane, provides a widely used biomarker for monitoring presynaptic dopaminergic function and is widely used as an adjunct to clinical diagnosis of Parkinson’s disease (PD) and as a research tool for assessing longitudinal course and pharmacodynamic response in therapeutic trials of novel PD treatments.

Method: SURE-PD3 was designed to assess whether urate-elevating inosine treatment slows PD clinical decline. The trial was terminated after an interim analysis showed futility. DaT imaging was performed 1 month before baseline and 22 months after randomization to placebo or active-drug in 154 participants. DAT^IQ uses canonical images of the non-displaceable and specific [123I]Ioflupane signal to enable an image-based regression in stereotaxic space which yields an estimate of DaT_Load (%) where 100% corresponds to the average DaT load in healthy subjects and 0% denotes a hypothetical absence of DaT in the striatum. Longitudinal DaT_Load estimates were compared to SBR values for caudate, putamen and striatum previously estimated for SURE-PD3.

Results: The global, ipsilateral, and contralateral DaT_Load were estimated successfully and compared to previous SBR measures (Figure 1). All DaT_Load measures declined ~10% per year on average in the 154 PD subjects. The comparison between DAT^IQ and SBR outcome measures demonstrated that DaT^IQ provided increased power to detect longitudinal changes of DaT signal (15 — 92% higher cohen’s d effect size, depending on the SBR target ROI). Using, these effect sizes, indicates that DAT^IQ could reduce sample size requirements for trials designed to detect DaT changes by 36% (caudate SBR), 62% (putamen SBR), and 25% (striatum SBR). (Table 1)

Conclusion: DAT^IQ provides increased sensitivity to change in DaT among PD patients relative to the currently used SBR analytical approach, permitting a reduction in required sample size or an increase in power to detect pharmacodynamic response. These results demonstrate the value of DAT^IQ as an analytical tool for future PD imaging trials.

References: [1] Parkinson Study Group SURE-PD Investigators, Schwarzschild MA, Ascherio A, Beal MF, Cudkowicz ME, Curhan GC, Hare JM, Hooper DC, Kieburtz KD, Macklin EA, Oakes D, Rudolph A, Shoulson I, Tennis MK, Espay AJ, Gartner M, Hung A, Bwala G, Lenehan R, Encarnacion E, Ainslie M, Castillo R, Togasaki D, Barles G, Friedman JH, Niles L, Carter JH, Murray M, Goetz CG, Jaglin J, Ahmed A, Russell DS, Cotto C, Goudreau JL, Russell D, Parashos SA, Ede P, Saint-Hilaire MH, Thomas CA, James R, Stacy MA, Johnson J, Gauger L, Antonelle de Marcaida J, Thurlow S, Isaacson SH, Carvajal L, Rao J, Cook M, Hope-Porche C, McClurg L, Grasso DL, Logan R, Orme C, Ross T, Brocht AF, Constantinescu R, Sharma S, Venuto C, Weber J, Eaton K. Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. JAMA Neurol. 2014 Feb;71(2):141-50. doi: 10.1001/jamaneurol.2013.5528. PMID: 24366103; PMCID: PMC3940333.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dat-iq-improves-power-to-detect-longitudinal-change-in-dat-deficit-in-sure-pd3/