A Novel PET Imaging Probe for the Detection and Monitoring of Translocator Protein 18 kDa Expression in Pathological Disorders

Perrone, Mara; Moon, Byung Seok; Park, Hyun Soo; Laquintana, Valentino; Jung, Jae Ho; Cutrignelli, Annalisa; Lopedota, Angela; Franco, Massimo; Kim, Sang Eun; Lee, Byung Chul; Denora, Nunzio

doi:10.1038/srep20422

Cited by 47 publications

(47 citation statements)

References 33 publications

(43 reference statements)

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“…Smal l-animal in vivo imaging has revealed its striking potential as a research tool to noninvasively study the onset and progression of multiple diseases (1,2), to evaluate novel PET tracers (3,4), or to contribute to drug development (1,5,6). It further enables in vivo therapy monitoring and bridges the gap of straightforward translation to clinical applications (1,3,7,8).…”

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confidence: 99%

Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study

et al. 2019

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The standardization of preclinical imaging is a key factor to ensure the reliability, reproducibility, validity, and translatability of preclinical data. Preclinical standardization has been slowly progressing in recent years and has mainly been performed within a single institution, whereas little has been done in regards to multicenter standardization between facilities. This study aimed to investigate the comparability among preclinical imaging facilities in terms of PET data acquisition and analysis. In the first step, basic PET scans were obtained in 4 different preclinical imaging facilities to compare their standard imaging protocol for 18 F-FDG. In the second step, the influence of the personnel performing the experiments and the experimental equipment used in the experiment were compared. In the third step, the influence of the image analysis on the reproducibility and comparability of the acquired data was determined. Distinct differences in the uptake behavior of the 4 standard imaging protocols were determined for the investigated organs (brain, left ventricle, liver, and muscle) due to different animal handling procedures before and during the scans (e.g., fasting vs. nonfasting, glucose levels, temperature regulation vs. constant temperature warming). Significant differences in the uptake behavior in the brain were detected when the same imaging protocol was used but executed by different personnel and using different experimental animal handling equipment. An influence of the person analyzing the data was detected for most of the organs, when the volumes of interest were manually drawn by the investigators. Coregistration of the PET to an MR image and drawing the volume of interest based on anatomic information yielded reproducible results among investigators. It has been demonstrated that there is a huge demand for standardization among multiple institutions.

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Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study

et al. 2019

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“…The partition coefficient of 1 (Log D = 2.15 ± 0.02 vs. 1.08 ± 0.02 for 3 ) indicated a relatively low lipophilicity compared to that of fluorine-substituted imidazo [1,2- a ]pyridine acetamide analogs (i.e., 3.00 ± 0.03 for [ 18 F]CB251) prepared in our previous investigations [32]. However, the lower lipophilicity did not prevent the uptake of 1 in tumor cells (see Section 2.3).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Evaluation of Tricarbonyl 99mTc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer

Choi

Iacobazzi

Perrone

et al. 2016

IJMS

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The 18-kDa translocator protein (TSPO) levels are associated with brain, breast, and prostate cancer progression and have emerged as viable targets for cancer therapy and imaging. In order to develop highly selective and active ligands with a high affinity for TSPO, imidazopyridine-based TSPO ligand (CB256, 3) was prepared as the precursor. 99mTc- and Re-CB256 (1 and 2, respectively) were synthesized in high radiochemical yield (74.5% ± 6.4%, decay-corrected, n = 5) and chemical yield (65.6%) by the incorporation of the [99mTc(CO)3(H2O)3]+ and (NEt4)2[Re(CO)3Br3] followed by HPLC separation. Radio-ligand 1 was shown to be stable (>99%) when incubated in human serum for 4 h at 37 °C with a relatively low lipophilicity (logD = 2.15 ± 0.02). The rhenium-185 and -187 complex 2 exhibited a moderate affinity (Ki = 159.3 ± 8.7 nM) for TSPO, whereas its cytotoxicity evaluated on TSPO-rich tumor cell lines was lower than that observed for the precursor. In vitro uptake studies of 1 in C6 and U87-MG cells for 60 min was found to be 9.84% ± 0.17% and 7.87% ± 0.23% ID, respectively. Our results indicated that 99mTc-CB256 can be considered as a potential new TSPO-rich cancer SPECT imaging agent and provides the foundation for further in vivo evaluation.

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“…The benefit of using 11 C-labeled tracers is their lower radiation burden when serial PET scans are performed in the same subject. Very recently, 18 F-fluoroethyl derivatives of CB184 were synthesized and show promising properties for TSPO imaging to detect neuroinflammation [35]. …”

Section: Discussionmentioning

confidence: 99%

Assessment of safety, efficacy, and dosimetry of a novel 18-kDa translocator protein ligand, [11C]CB184, in healthy human volunteers

et al. 2017

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Background N,N-di-n-propyl-2-[2-(4-[11C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([11C]CB184) is a novel selective radioligand for the 18-kD translocator protein (TSPO), which is upregulated in activated microglia in the brain, and may be useful in positron emission tomography (PET). We examined the safety, radiation dosimetry, and initial brain imaging with [11C]CB184 in healthy human volunteers.ResultsDynamic [11C]CB184 PET scans (90 min) were performed in five healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined with high-performance liquid chromatography. No serious adverse events occurred in any of the subjects throughout the study period. [11C]CB184 was metabolized in the periphery: 36.7% ± 5.7% of the radioactivity in plasma was detected as the unchanged form after 60 min. The total distribution volume (V T) was estimated with a two-tissue compartment model. The V T of [11C]CB184 was highest in the thalamus (5.1 ± 0.4), followed by the cerebellar cortex (4.4 ± 0.2), and others. Although regional differences were small, the observed [11C]CB184 binding pattern was consistent with the TSPO distribution in the normal human brain. Radiation dosimetry was determined in three healthy male subjects using a serial whole-body PET scan acquired over 2 h after [11C]CB184 injection. [11C]CB184 PET demonstrated high uptake in the gallbladder at a later time (>60 min). In urine obtained approximately 100 min post-injection, 0.3% of the total injected radioactivity was recovered, indicating hepatobiliary excretion of radioactivity. The absorbed dose (μGy/MBq) was highest in the kidneys (21.0 ± 0.5) followed by the lungs (16.8 ± 2.7), spleen (16.6 ± 6.6), and pancreas (16.5 ± 2.2). The estimated effective dose for [11C]CB184 was 5.9 ± 0.6 μSv/MBq.ConclusionsThis initial evaluation indicated that [11C]CB184 is feasible for imaging of TSPO in the brain.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-017-0271-6) contains supplementary material, which is available to authorized users.

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A Novel PET Imaging Probe for the Detection and Monitoring of Translocator Protein 18 kDa Expression in Pathological Disorders

Cited by 47 publications

References 33 publications

Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study

Reproducibility and Comparability of Preclinical PET Imaging Data: A Multicenter Small-Animal PET Study

Synthesis and Evaluation of Tricarbonyl 99mTc-Labeled 2-(4-Chloro)phenyl-imidazo[1,2-a]pyridine Analogs as Novel SPECT Imaging Radiotracer for TSPO-Rich Cancer

Assessment of safety, efficacy, and dosimetry of a novel 18-kDa translocator protein ligand, [11C]CB184, in healthy human volunteers

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