Comparison of Taiwanese and European Calibration Factors for Heart-to-Mediastinum Ratio in Multicenter 123I-mIBG Phantom Studies.

Background: Cross-calibration of 123I-labeled meta-iodobenzylguanidine (mIBG) myocardial-derived indices is essential to extrapolate findings from several clinical centers. Here, we conducted a phantom study to generate conversion coefficients for the calibration of heart-to-mediastinum ratios and compare them between Taiwan and Europe. Methods: We used an acrylic phantom dedicated to 123I-mIBG planar imaging to calculate the conversion coefficients of 136 phantom images derived from 36 Taiwanese institutions. A European phantom image database including 191 images from 27 institutions was used. Conversion coefficients were categorized into five collimator types: low-energy (LE) high-resolution (LEHR), LE general-purpose (LEGP), extended LEGP (ELEGP), medium-energy (ME) GP (MEGP), and ME low-penetration (MELP) collimators. Results: The conversion coefficients were 0.53 ± 0.039, 0.59 ± 0.032, 0.79 ± 0.032, 0.96 ± 0.038, and 0.99 ± 0.050 for LEHR, LEGP, ELEGP, MEGP, and MELP collimators, respectively. The Taiwanese and European conversion coefficients for the LEHR, LEGP, and MELP collimators did not significantly differ. The coefficient of variation was slightly higher for the Taiwanese than the European conversion coefficients (3.7%-7.5% vs. 2.3%-5.6%). Conclusions: We calculated conversion coefficients for various types of collimators used in Taiwan using a 123I-mIBG phantom. In general, the Taiwanese and European conversion coefficients were comparable. These findings further corroborated and highlighted the need for 123I-mIBG standardization using the phantom-determined conversion coefficients.

Machine learning-based prediction of conversion coefficients for I-123 metaiodobenzylguanidine heart-to-mediastinum ratio.

PURPOSE: We developed a method of standardizing the heart-to-mediastinal ratio in 123I-labeled meta-iodobenzylguanidine (MIBG) images using a conversion coefficient derived from a dedicated phantom. This study aimed to create a machine-learning (ML) model to estimate conversion coefficients without using a phantom. METHODS: 210 Monte Carlo (MC) simulations of 123I-MIBG images to obtain conversion coefficients using collimators that differed in terms of hole diameter, septal thickness, and length. Simulated conversion coefficients and collimator parameters were prepared as training datasets, then a gradient-boosting ML was trained to estimate conversion coefficients from collimator parameters. Conversion coefficients derived by ML were compared with those that were MC simulated and experimentally derived from 613 phantom images. RESULTS: Conversion coefficients were superior when estimated by ML compared with the classical multiple linear regression model (root mean square deviations: 0.021 and 0.059, respectively). The experimental, MC simulated, and ML-estimated conversion coefficients agreed, being, respectively, 0.54, 0.55, and 0.55 for the low-; 0.74, 0.70, and 0.72 for the low-middle; and 0.88, 0.88, and 0.88 for the medium-energy collimators. CONCLUSIONS: The ML model estimated conversion coefficients without the need for phantom experiments. This means that conversion coefficients were comparable when estimated based on collimator parameters and on experiments.

Calibrated scintigraphic imaging procedures improve quantitative assessment of the cardiac sympathetic nerve activity.

The 123I-labeled meta-iodobenzylguanidine (MIBG) is an analogue of noradrenaline that can evaluate cardiac sympathetic activity in scintigraphy. Quantitative analysis of 123I-MIBG images has been verified in patients with heart failure and neurodegenerative diseases. However, quantitative results differ due to variations in scintigraphic imaging procedures. Here, we created and assessed the clinical feasibility of a calibration method for 123I-MIBG imaging. The characteristics of scintigraphic imaging systems were determined using an acrylic calibration phantom to generate a multicenter phantom imaging database. Calibration factors corresponding to the scintigraphic imaging procedures were calculated from the database and applied to a clinical study. The results of this study showed that the calibrated analysis eliminated inter-institutional differences among normal individuals. In summary, our standardization methodology for 123I-MIBG scintigraphy could provide the basis for improved diagnostic precision and better outcomes for patients.

In vivo SPECT imaging of amyloid-ß deposition with radioiodinated imidazo[1,2-a]pyridine derivative DRM106 in a mouse model of Alzheimer's disease.

UNLABELLED: Noninvasive determination of amyloid-ß peptide (Aß) deposition has important significance for early diagnosis and medical intervention for Alzheimer's disease (AD). In the present study, we investigated the availability of radiolabeled DRM106 ((123/125)I-DRM106 [6-iodo-2-[4-(1H-3-pyrazolyl)phenyl]imidazo[1,2-a]pyridine]), a compound with sufficient affinity for the synthesis of human Aß fibrils and satisfactory metabolic stability, as a SPECT ligand in living brains. METHOD: The sensitivity of (125)I-DRM106 for detecting Aß deposition was compared with that of (125)I-IMPY (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), a well-known amyloid SPECT ligand, by ex vivo autoradiographic analyses in 18-mo-old amyloid precursor protein transgenic mice. To verify the sensitivity and quantitation of radiolabeled DRM106 for in vivo imaging, we compared the detectability of Aß plaques with (123)I-DRM106 and a well-known amyloid PET agent, (11)C-labeled Pittsburgh compound B ((11)C-PiB), in 29-mo-old transgenic mice and age-matched nontransgenic littermates. Additionally, we compared the binding characteristics of (125)I-DRM106 with those of (11)C-PiB and (11)C-PBB3, which selectively bind to Aß plaques and preferentially to tau aggregates, respectively, in postmortem AD brain sections. RESULTS: Ex vivo autoradiographic analysis showed that measurement with (125)I-DRM106 has a higher sensitivity for detecting Aß accumulation than with (125)I-IMPY in transgenic mice. SPECT imaging with (123)I-DRM106 also successfully detected Aß deposition in living aged transgenic mice and showed strong correlation (R = 0.95, P < 0.01) in quantitative analysis for Aß plaque detection by PET imaging with (11)C-PiB, implying that sensitivity and quantitation of SPECT imaging with (123)I-DRM106 are almost as good as (11)C-PiB PET for the detectability of Aß deposition. Further, the addition of nonradiolabeled DRM106 fully blocked the binding of (125)I-DRM106 and (11)C-PiB, but not (11)C-PBB3, to AD brain sections, and (125)I-DRM106 showed a lower binding ratio of the diffuse plaque-rich lateral temporal cortex to the dense-cored/neuritic plaque-rich hippocampal CA1 area, compared with (11)C-PiB. CONCLUSION: All of these data demonstrated the high potential of (123)I-DRM106 for amyloid imaging in preclinical and clinical application, and it might more preferentially detect dense-cored/neuritic amyloid deposition, which is expected to be closely associated with neuropathologic changes of AD.

Biological evaluation of the radioiodinated imidazo[1,2-a]pyridine derivative DRK092 for amyloid-ß imaging in mouse model of Alzheimer's disease.

Non-invasive determination of amyloid-ß peptide (Aß) deposition has important significance for early diagnosis and medical intervention in Alzheimer's disease (AD). In this study, we investigated the availability of a radioiodinated imidazo[1,2-a]pyridine derivative, termed (125)I-DRK092, as single photon emission computed tomography (SPECT) ligand for in vivo detection of Aß deposition. DRK092 showed high binding affinity for either synthetic human Aß fibrils or brain homogenates from amyloid precursor protein transgenic (Tg) mouse (PS1-ki/JU-Tg2576) and AD patient with a dissociation constant (Kd) of one-digit nM, and excellent brain permeability (peak value of uptake: approximately 0.9% of injection dose/g rat brain). Ex vivo autoradiographic analysis showed that measurement with (125)I-DRK092 has higher sensibility for detecting Aß accumulation than with (125)I-IMPY, a well-known amyloid SPECT ligand, in Tg mice. In vitro autoradiography with (125)I-DRK092 also confirmed higher accumulation of radioactivity in the cortical area, enriched with Aß plaques, of Tg mouse and AD patient brains, as compared with the corresponding areas in non-Tg mouse and healthy control brains. All the data presented above lead us to draw the conclusion that radioiodinated DRK092 is a potential SPECT ligand for amyloid imaging in AD.

Synthesis and biological evaluation of novel radioiodinated imidazopyridine derivatives for amyloid-ß imaging in Alzheimer's disease.

Non-invasive detection for amyloid-ß peptide (Aß) deposition has important significance for the early diagnosis and medical intervention for Alzheimer's disease (AD). In this study, we developed a series of imidazopyridine derivatives as potential imaging agents for single-photon emission computed tomography (SPECT). Two of them, compounds DRK092 and DRM106, showed higher affinity for synthetic human Aß 1-40 fibrils than did the well-known amyloid-imaging agent IMPY. A metabolite analysis revealed brain-permeable radioactive metabolites of (125)I-labeled DRK092 and IMPY; no radioactive metabolites from (125)I-labeled DRM106 ([(125)I]DRM106) were detected. In addition, in vitro autoradiography clearly demonstrated specific binding of [(125)I]DRM106 in the hippocampal region of AD enriched with Aß plaques. Thus, our results strongly suggested that compound DRM106 can be used as an imaging agent for SPECT to detect Aß deposition in AD brain.