Single-site 123I-FP-CIT reference values from individuals with non-degenerative parkinsonism—comparison with values from healthy volunteers

Abstract

Iodine 123-radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123 I-FP-CIT) SPECT can be performed to distinguish degenerative forms of movement disorders/parkinsonism/tremor from other entities such as idiopathic tremor or drug-induced parkinsonism. For equivocal cases, semi-quantification and comparison to reference values are a necessary addition to visual interpretation of 123 I-FP-CIT scans. To overcome the challenges of multi-center recruitment and scanning of healthy volunteers, we generated 123 I-FP-CIT reference values from individuals with various neurological conditions but without dopaminergic degeneration, scanned at a single center on the same SPECT-CT system following the same protocol, and compared them to references from a multi-center database built using healthy volunteers' data. Methods: From a cohort of 1884 patients, we identified 237 subjects (120 men, 117 women, age range 16-88 years) through a two-stage selection process. Every patient had a final clinical diagnosis after a mean follow-up of 4.8 ± 1.3 years. Images were reconstructed using (1) Flash3D with scatter and CT-based attenuation corrections (AC) and (2) filtered back projection with Chang AC. Volume-of-interest analysis was performed using a commercial software to calculate specific binding ratios (SBRs), caudate-to-putamen ratios, and asymmetry values on different striatal regions. Generated reference values were assessed according to age and gender and compared with those from the ENC-DAT study, and their robustness was tested against a cohort of patients with different diagnoses. Results: Age had a significant negative linear effect on all SBRs. Overall, the reduction rate per decade in SBR was between 3.80 and 5.70%. Women had greater SBRs than men, but this gender difference was only statistically significant for the Flash3D database. Linear regression was used to correct for age-dependency of SBRs and to allow comparisons to age-matched reference values and "normality" limits. Generated regression parameters and their 95% confidence intervals (CIs) were comparable to corresponding European Normal Control Database of DaTscan (ENC-DAT) results. For example, 95% CI mean slope for the striatum in women is − 0.015 ([− 0.019, − 0.011]) for the Flash3D database versus − 0.015 ([− 0.021, − 0.009]) for ENC-DAT. Caudate-toputamen ratios and asymmetries were not influenced by age or gender.

Binding potential changes of SERT in patients with depression are associated with remission: A prospective [¹²³I]β-CIT-SPECT study.

“…Furthermore, the SSRI treatment led to statistically significantly lower binding ratios in SERT-rich brain areas (Booij et al, 2007). SERT and DAT have been shown to be distributed differently among brain regions (de Win et al, 2005; Fahmi et al, 2020). SERT binding potential in unmedicated patients seems to be reduced, especially in more severely affected individuals with depression.…”

Serial changes of I-123 FP-CIT SPECT binding asymmetry in Parkinson's disease: Analysis of the PPMI data

“…The SBR asymmetry index that was used in previous studies (asymmetry index by method 1) was calculated as the absolute ratio of difference to average striatal SBRs ( 7 , 11 – 16 ). Although there was a significant decrease in the putaminal asymmetry index using method 1 after the 1-year follow-up mark, there was no notable pattern of changes during the entire follow-up period.…”

“…Some studies have reported higher SBRs in females of NCs ( 24 , 25 ), while others reported no difference according to gender ( 26 , 27 ). Furthermore, this gender related difference of SBRs were suggested to be dependent on the image reconstruction method ( 11 , 28 ). Further studies with an age- and gender-matched comparison with a larger number of NCs may be needed to clarify this issue.…”

“…The 1st method (method 1) was calculated as: |SBRleft– SBRright|/[(SBRleft + SBRright)/2] ×100. Asymmetry index by method 1 was calculated based on previous studies ( 7 , 11 – 16 ). In this study, we adopted a new method for the calculation of the asymmetry index (method 2): |SBRleft– SBRright|/SBR values of age-matched normal controls ×100.…”

Semi-quantitative analysis of visually normal 123I-FP-CIT across three large databases revealed no difference between control and patients

“…A potential limitation of the use of these databases is the additional instrumental variance in SBR values caused by the heterogeneity in equipment, despite the inter-center (inter-system) calibration, which could reduce their sensitivity [ 9 , 10 ] . Alternatively, SBR reference values are obtained locally and retrospectively from normal 123 I-FP-CIT routine examinations of a patient group presenting heterogeneous suspected diagnoses, but without dopaminergic neurodegenerative pathology, after a follow-up period lasting up to 5 years [ 11 , 12 ].…”