The Characterization of 18F-hGTS13 for Molecular Imaging of xC− Transporter Activity with PET

Beinat, Corinne; Gowrishankar, Gayatri; Shen, Bin; Alam, Israt S.; Robinson, Elise; Haywood, Tom; Azevedo, E. Carmen; Castillo, Jessa B.; Ilovich, Ohad; Koglin, Norman; Schmitt‐Willich, Heribert; Berndt, Mathias; Mueller, André; Zerna, Marion; Srinivasan, Ananth; Gambhir, Sanjiv S.

doi:10.2967/jnumed.119.225870

Cited by 11 publications

(13 citation statements)

References 36 publications

(73 reference statements)

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“…Biodistribution analysis in rodents showed rapid blood clearance via the kidneys and low background activity, providing high contrast for tumor imaging. Radiosynthesis and preclinical data of 18 F-hGTS13 and 18 F-5-fluoro-L-aminosuberic acid, other tracers taken up by system x C À and used for tumor visualization, were described recently in tumor models (17)(18)(19). Pilot clinical studies examining safety, dosimetry, and biodistribution of 18 F-FSPG in healthy volunteers (20,21) and the tumor detection in various tumor entities showed promising results (22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-glutamate (18F-FSPG) for PET/CT Imaging in Patients with Newly Diagnosed and Recurrent Prostate Cancer

Park

Kumar

et al. 2020

Clinical Cancer Research

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◥Purpose: (4S)-4-(3-[ 18 F]Fluoropropyl)-L-glutamic acid ( 18 F-FSPG) is a radiopharmaceutical for PET imaging of system x C À activity, which can be upregulated in prostate cancer. We present data on the first evaluation of patients with newly diagnosed or recurrent prostate cancer with this radiopharmaceutical.Experimental Design: Ten patients with primary and 10 patients with recurrent prostate cancer were enrolled in this prospective multicenter study. After injection of 300 MBq of 18 F-FSPG, three whole-body PET/CT scans were obtained. Visual analysis was compared with step-section histopathology when available as well as other imaging studies and clinical outcomes. Metabolic parameters were measured semiquantitatively. Expression levels of xCT and CD44 were evaluated by IHC for patients with available tissue samples.Results: 18 F-FSPG PET showed high tumor-to-background ratios with a relatively high tumor detection rate on a per-patient (89%) and per-lobe (87%) basis. The sensitivity was slightly higher with imaging at 105 minutes in comparison with 60 minutes. The maximum standardized uptake values (SUV max ) for cancer was significantly higher than both normal (P < 0.005) and benign pathology (P ¼ 0.011), while there was no significant difference between normal and benign pathology (P ¼ 0.120). In the setting of recurrence, agreement with standard imaging was demonstrated in 7 of 9 patients (78%) and 13 of 18 lesions (72%), and revealed true local recurrence in a discordant case. 18 F-FSPG accumulation showed moderate correlation with CD44 expression.Conclusions: 18 F-FSPG is a promising tumor imaging agent for PET that seems to have favorable biodistribution and high cancer detection rate in patients with prostate cancer. Further studies are warranted to determine the diagnostic value for both initial staging and recurrence, and how it compares with other investigational radiotracers and conventional imaging modalities.

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Section: Introductionmentioning

confidence: 99%

Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-glutamate (18F-FSPG) for PET/CT Imaging in Patients with Newly Diagnosed and Recurrent Prostate Cancer

Park

Kumar

et al. 2020

Clinical Cancer Research

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“…Following cystine's uptake, it is rapidly reduced to cysteine, the rate limiting precursor for glutathione biosynthesis, placing system xCas a central regulator of antioxidant homeostasis (17). Elevated system xCactivity has been exploited by PET imaging tracers such as (4S)-4-(3-18 F-fluoropropyl)-L-glutamate ( 18 F-FSPG) (18), 18 F-5-fluoroaminosuberic acid (19), and 18 F-hGTS13 (20). Tumor retention of 18 F-FSPG is redox-sensitive, mediated by the concentration gradient of cystine across the plasma membrane.…”

Section: Imaging the Tumor Antioxidant Responsementioning

confidence: 99%

Latest Advances in Imaging Oxidative Stress in Cancer

Greenwood

Witney

2021

J Nucl Med

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Oxidative stress is the imbalance of harmful reactive oxygen species (ROS) and the action of neutralizing antioxidant mechanisms. If left unchecked, the deleterious effects of oxidative stress results in damage to DNA, proteins, and membranes, ultimately leading to cell death. Tumors are highly proliferative and consequently generate high levels of mitochondrial ROS. To compensate and maintain redox homeostasis, cancer cells upregulate protective antioxidant pathways, which are further amplified in drug-resistant tumors. This review provides an overview of the latest molecular imaging techniques designed to image oxidative stress in cancer. New probes are now able to assess heterogeneous ROS and antioxidant production within tumors and across lesions.Together, the non-invasive imaging of these dynamic processes holds great promise for treatment response monitoring, prediction of drug resistance, and may provide insight into the metastatic potential of tumors.

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“…(S)-4-(3-18 F-Fluoropropyl)-L-Glutamic Acid ([ 18 F]FSPG) is a radiolabeled non-natural amino acid used for PET imaging of the amino acid transporter, system x C - [7][8][9][10][11][12][13][14][15]. The elevated expression of system x C in a wide range of cancer types can be targeted by radiotracers specific to this transporter to provide high contrast images of tumors [7,11,[16][17][18]. Clinically, [ 18 F]FSPG has been evaluated in hepatocellular carcinoma, non-small cell lung cancer, prostate cancer, and intracranial malignancies [9,15,18,19].…”

Section: Introductionmentioning

confidence: 99%

Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

et al. 2021

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Purpose (S)-4-(3-18F-Fluoropropyl)-ʟ-Glutamic Acid ([18F]FSPG) is a radiolabeled non-natural amino acid that is used for positron emission tomography (PET) imaging of the glutamate/cystine antiporter, system xC-, whose expression is upregulated in many cancer types. To increase the clinical adoption of this radiotracer, reliable and facile automated procedures for [18F]FSPG production are required. Here, we report a cassette-based method to produce [18F]FSPG at high radioactivity concentrations from low amounts of starting activity. Procedures An automated synthesis and purification of [18F]FSPG was developed using the GE FASTlab. Optimization of the reaction conditions and automated manipulations were performed by measuring the isolated radiochemical yield of [18F]FSPG and by assessing radiochemical purity using radio-HPLC. Purification of [18F]FSPG was conducted by trapping and washing of the radiotracer on Oasis MCX SPE cartridges, followed by a reverse elution of [18F]FSPG in phosphate-buffered saline. Subsequently, the [18F]FSPG obtained from the optimized process was used to image an animal model of non-small cell lung cancer. Results The optimized protocol produced [18F]FSPG in 38.4 ± 2.6 % radiochemical yield and >96 % radiochemical purity with a molar activity of 11.1 ± 7.7 GBq/μmol. Small alterations, including the implementation of a reverse elution and an altered Hypercarb cartridge, led to significant improvements in radiotracer concentration from <10 MBq/ml to >100 MBq/ml. The improved radiotracer concentration allowed for the imaging of up to 20 mice, starting with just 1.5 GBq of [18F]Fluoride. Conclusions We have developed a robust and facile method for [18F]FSPG radiosynthesis in high radiotracer concentration, radiochemical yield, and radiochemical purity. This cassette-based method enabled the production of [18F]FSPG at radioactive concentrations sufficient to facilitate large-scale preclinical experiments with a single prep of starting activity. The use of a cassette-based radiosynthesis on an automated synthesis module routinely used for clinical production makes the method amenable to rapid and widespread clinical translation.

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The Characterization of ¹⁸F-hGTS13 for Molecular Imaging of x_C⁻ Transporter Activity with PET

Cited by 11 publications

References 36 publications

Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-glutamate (18F-FSPG) for PET/CT Imaging in Patients with Newly Diagnosed and Recurrent Prostate Cancer

Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-glutamate (18F-FSPG) for PET/CT Imaging in Patients with Newly Diagnosed and Recurrent Prostate Cancer

Latest Advances in Imaging Oxidative Stress in Cancer

Robust and Facile Automated Radiosynthesis of [18F]FSPG on the GE FASTlab

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