Fully automated radiosynthesis of [11C]PBR28, a radiopharmaceutical for the translocator protein (TSPO) 18kDa, using a GE TRACERlab FXC-Pro

Hoareau, Raphaël; Shao, Xia; Henderson, Bradford D.; Scott, Peter J. H.

doi:10.1016/j.apradiso.2012.03.006

Cited by 9 publications

(8 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11 C-PBR28 was synthesized as described in the literature [ 14 , 15 ]. At days 3, 7, and 14 after PPE exposure, sets of APPE and IPPE controls were imaged dynamically on a microPET R4 scanner (Concorde/Siemens Microsystems, Knoxville, TN, USA) for 90 min after IV injection of approximately 37 MBq 18 F-FDG [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

Utility of 18 F-FDG and 11C-PBR28 microPET for the assessment of rat aortic aneurysm inflammation

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundThe utility of 18 F-FDG and 11C-PBR28 to identify aortic wall inflammation associated with abdominal aortic aneurysm (AAA) development was assessed.MethodsUtilizing the porcine pancreatic elastase (PPE) perfusion model, abdominal aortas of male Sprague-Dawley rats were infused with active PPE (APPE, AAA; N = 24) or heat-inactivated PPE (IPPE, controls; N = 16). Aortic diameter increases were monitored by ultrasound (US). Three, 7, and 14 days after induction, APPE and IPPE rats were imaged using 18 F-FDG microPET (approximately 37 MBq IV) and compared with 18 F-FDG autoradiography (approximately 185 MBq IV) performed at day 14. A subset of APPE (N = 5) and IPPE (N = 6) animals were imaged with both 11C-PBR28 (approximately 19 MBq IV) and subsequent 18 F-FDG (approximately 37 MBq IV) microPET on the same day 14 days post PPE exposure. In addition, autoradiography of the retroperitoneal torso was performed after 11C-PBR28 (approximately 1,480 MBq IV) or 18 F-FDG (approximately 185 MBq IV) administration at 14 days post PPE exposure. Aortic wall-to-muscle ratios (AMRs) were determined for microPET and autoradiography. CD68 and translocator protein (TSPO) immunohistochemistry (IHC), as well as TSPO gene expression assays, were performed for validation.ResultsMean 3 (p = 0.009), 7 (p < 0.0001) and 14 (p < 0.0001) days aortic diameter increases were significantly greater for APPE AAAs compared to IPPE controls. No significant differences in 18 F-FDG AMR were determined at days 3 and 7 post PPE exposure; however, at day 14, the mean 18 F-FDG AMR was significantly elevated in APPE AAAs compared to IPPE controls on both microPET (p = 0.0002) and autoradiography (p = 0.02). Similarly, mean 11C-PBR28 AMR was significantly increased at day 14 in APPE AAAs compared to IPPE controls on both microPET (p = 0.04) and autoradiography (p = 0.02). For APPE AAAs, inhomogeneously increased 18 F-FDG and 11C-PBR28 uptake was noted preferentially at the anterolateral aspect of the AAA. Compared to controls, APPE AAAs demonstrated significantly increased macrophage cell counts by CD68 IHC (p = 0.001) as well as increased TSPO staining (p = 0.004). Mean TSPO gene expression for APPE AAAs was also significantly elevated compared to IPPE controls (p = 0.0002).ConclusionRat AAA wall inflammation can be visualized using 18 F-FDG and 11C-PBR28 microPET revealing regional differences of radiotracer uptake on microPET and autoradiography. These results support further investigation of 18 F-FDG and 11C-PBR28 in the noninvasive assessment of human AAA development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-014-0020-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

Utility of 18 F-FDG and 11C-PBR28 microPET for the assessment of rat aortic aneurysm inflammation

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…[ 11 C]PBR28 was synthesized using modified GE Tracerlab FX C Pro based on the method of Shao et al [17]. Briefly, the precursor, desmethyl-PBR28 TBA salt (1 mg) was dissolved into absolute ethanol (100 µL), loaded onto the 2 mL stainless steel HPLC loop, and conditioned with nitrogen gas for 20 seconds at 10 mL/min.…”

Section: Methodsmentioning

confidence: 99%

Imaging of carrageenan-induced local inflammation and adjuvant-induced systemic arthritis with [11C]PBR28 PET

Shao

Wang

English

et al. 2013

Nuclear Medicine and Biology

Self Cite

View full text Add to dashboard Cite

Introduction [11C]PBR28 binding to translocator protein (TSPO) was evaluated for imaging of acute and chronic inflammation using two established rat models. Methods Acute inflammation was induced by local Carrageenan-injection into the paw of Fisher 344 rats (model A). T-cell mediated adjuvant arthritis was induced by heat-inactivated Mycobacterium butyricum injection in Lewis rats (model B). Micro-PET scan was performed after injection of approximately 35 MBq [11C]PBR28. In model A, volumes of interest (VOIs) were defined in the paw of Fisher 344 rats (n=6) with contralateral sham treatment as control. For model B, VOIs were defined in the tail, sacroiliac joints, hips, knees and thigh muscles of M. butyricum treated animals (n=8) and compared with sham-treated controls (n=4). The peak 11C-PBR28 SUV (SUVpeak) and area under the curve (AUCSUV) of 60-minute time-activity data were calculated. Immunohistochemistry for CD68, a macrophage stain, was performed from paw tissues. In addition, the [11C]PBR28 cell uptake was measured in lipopolysaccharide (LPS)-stimulated and non-stimulated macrophage cultures. Results LPS-stimulated macrophages displayed dose-dependent increased [11C]PBR28 uptake, which was blocked by non-labeled PBR28. In both models, radiotracer uptake of treated lesions increased rapidly within minutes and displayed overall accumulative kinetics. The SUVpeak and AUCSUV of Carrageenan-treated paws was significantly increased compared to controls. Also, the [11C]PBR28 uptake ratio of Carrageenan-treated vs. sham-treated paw correlated significantly with CD68 staining ratios of the same animals. In adjuvant arthritis, significantly increased [11C]PBR28 SUVpeak and AUCSUV values were identified at the tail, knees, and sacroiliac joints, while no significant differences were identified in the lumbar spine and hips. Conclusions Based on our initial data, [11C]PBR28 PET appears to have potential for imaging of various inflammatory processes involving macrophage activation.

show abstract

“…Using a slight modification of the previously reported methods [ 48 , 49 ], the [ 11 C]PBR28 p -phenol precursor, 6 , and the corresponding nonradioactive standard, PBR28, were synthesized in higher chemical yields and a shorter reaction time ( Scheme 2 ). Details of the synthesis have been provided in the “Supporting Information” folder.…”

Section: Resultsmentioning

confidence: 99%

Improved Automated Radiosynthesis of [11C]PBR28

Sai

2015

Sci. Pharm.

View full text Add to dashboard Cite

Microglial activation is commonly identified by elevated levels of the 18 kDa translocator protein (TSPO) in response to several inflammatory processes. [11C]PBR28 is one of the most promising PET tracers to image TSPO in both human and non-human primates. In this study, we optimized the radiolabeling procedure of [11C]PBR28 for higher radiochemical yield, radiochemical purity, and specific activity, which can be easily translated to any automated module for clinical trials. Time-activity curves (TACs) derived from the dynamic PET imaging of male rhesus monkey brains demonstrated that [11C]PBR28 had suitable kinetics with radiotracer accumulation observed in the caudate, putamen, cerebellum, and frontal cortex region.

show abstract

Fully automated radiosynthesis of [11C]PBR28, a radiopharmaceutical for the translocator protein (TSPO) 18kDa, using a GE TRACERlab FXC-Pro

Cited by 9 publications

References 10 publications

Utility of 18 F-FDG and 11C-PBR28 microPET for the assessment of rat aortic aneurysm inflammation

Utility of 18 F-FDG and 11C-PBR28 microPET for the assessment of rat aortic aneurysm inflammation

Imaging of carrageenan-induced local inflammation and adjuvant-induced systemic arthritis with [11C]PBR28 PET

Improved Automated Radiosynthesis of [11C]PBR28

Contact Info

Product

Resources

About