Biodistribution and Radiation Dosimetry of Deuterium-Substituted 18F-Fluoromethyl-[1, 2-2H4]Choline in Healthy Volunteers

Challapalli, Amarnath; Sharma, Rohini; Hallett, William A.; Kozlowski, Kasia; Carroll, Laurence; Bričkutė, Diana; Twyman, Frazer J.; Al‐Nahhas, Adil; Aboagye, Eric O.

doi:10.2967/jnumed.113.129577

Cited by 25 publications

(28 citation statements)

References 28 publications

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“…Should 18 F-fluoromethylcholine metabolism remain constant throughout the response-monitoring study, the performance of SUV AUC,WB , and to a lesser extent SUV, may be equivalent to SUV AUC,PP as a relative measure of response. Challapalli et al recently reported on a novel 18 F-labeled choline tracer that metabolizes less rapidly than 18 F-fluoromethylcholine, with parent fractions gradually decreasing to approximately 0.3 over the first hour after injection (25,26). With decreased interpatient variability in parent fractions, the performance of SUV and SUV AUC,WB may improve with respect to SUV AUC,PP .…”

Section: Discussionmentioning

confidence: 99%

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Geest

Metselaar²,

Storm³

2015

J Nucl Med

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Choline kinase is upregulated in prostate cancer, resulting in increased 18 F-fluoromethylcholine uptake. This study used pharmacokinetic modeling to validate the use of simplified methods for quantification of 18 F-fluoromethylcholine uptake in a routine clinical setting. Methods: Forty-minute dynamic PET/CT scans were acquired after injection of 204 ± 9 MBq of 18 F-fluoromethylcholine, from 8 patients with histologically proven metastasized prostate cancer. Plasma input functions were obtained using continuous arterial blood-sampling as well as using image-derived methods. Manual arterial blood samples were used for calibration and correction for plasma-to-blood ratio and metabolites. Time-activity curves were derived from volumes of interest in all visually detectable lymph node metastases. 18 F-fluoromethylcholine kinetics were studied by nonlinear regression fitting of several single-and 2-tissue plasma input models to the time-activity curves. Model selection was based on the Akaike information criterion and measures of robustness. In addition, the performance of several simplified methods, such as standardized uptake value (SUV), was assessed. Results: Best fits were obtained using an irreversible compartment model with blood volume parameter. Parent fractions were 0.12 ± 0.4 after 20 min, necessitating individual metabolite corrections. Correspondence between venous and arterial parent fractions was low as determined by the intraclass correlation coefficient (0.61). Results for image-derived input functions that were obtained from volumes of interest in bloodpool structures distant from tissues of high 18 F-fluoromethylcholine uptake yielded good correlation to those for the blood-sampling input functions (R 2 5 0.83). SUV showed poor correlation to parameters derived from full quantitative kinetic analysis (R 2 , 0.34). In contrast, lesion activity concentration normalized to the integral of the blood activity concentration over time (SUV AUC ) showed good correlation (R 2 5 0.92 for metabolite-corrected plasma; 0.65 for whole-blood activity concentrations). Conclusion: SUV cannot be used to quantify 18 F-fluoromethylcholine uptake. A clinical compromise could be SUV AUC derived from 2 consecutive static PET scans, one centered on a large blood-pool structure during 0-30 min after injection to obtain the blood activity concentrations and the other a whole-body scan at 30 min after injection to obtain lymph node activity concentrations.

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Section: Discussionmentioning

confidence: 99%

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Geest

Metselaar²,

Storm³

2015

J Nucl Med

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“…Our data suggest that PET imaging of radiolabeled choline may be used to detect PDAC, provided there is adequate delivery of the probe, as the desmoplastic stroma in pancreatic cancers may impede its delivery (4). A recent study detected a relatively high uptake, but a low residence time, of a radiolabeled choline tracer in the pancreas of normal volunteers (30), suggesting that PDAC may be detected using relatively long-lived radiolabeled choline PET tracers that allow imaging at later time points to achieve good systemic clearance (30). …”

Section: Discussionmentioning

confidence: 99%

Metabolic Imaging of Pancreatic Ductal Adenocarcinoma Detects Altered Choline Metabolism

Penet

Shah

Bharti

et al. 2015

Clinical Cancer Research

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Purpose Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal disease that develops relatively symptom-free and is therefore advanced at the time of diagnosis. The absence of early symptoms and effective treatments has created a critical need for identifying and developing new noninvasive biomarkers and therapeutic targets. Experimental Design We investigated the metabolism of a panel of PDAC cell lines in culture and noninvasively in vivo with 1H magnetic resonance spectroscopic imaging (MRSI) to identify noninvasive biomarkers and uncover potential metabolic targets. Results We observed elevated choline-containing compounds in the PDAC cell lines and tumors. These elevated choline-containing compounds were easily detected by increased total choline (tCho) in vivo, in spectroscopic images obtained from tumors. Principal component analysis of the spectral data identified additional differences in metabolites between HPNE and neoplastic PDAC cells. Molecular characterization revealed overexpression of choline kinase (Chk)-α, choline transporter 1 (CHT1), and choline transporter-like protein 1 (CTL1) in the PDAC cell lines and tumors. Conclusions Collectively, these data identify new metabolic characteristics of PDAC and reveal potential metabolic targets. Total choline detected with 1H MRSI may provide an intrinsic, imaging-probe independent biomarker to complement existing techniques in detecting PDAC. The expression of Chk-α, CHT1, and CTL1 may provide additional molecular markers in aspirated cytological samples.

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“…Bladder radioactivity, unlike other organs, was calculated, taking into account the bladder volume changes over the time course of the scan (12)(13)(14)(15). The effective dose (ED) was calculated using, first, the mean residence time over all subjects for each organ and, second, residence times for individual subjects with OLINDA/ EXM (version 1.1), which uses the organ weighting factors from ICRP 60 (16).…”

Section: Data Analysis Biodistribution and Dosimetrymentioning

confidence: 99%

Clinical Translation of a Click-Labeled ¹⁸F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

et al. 2016

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We conducted the first-in-human study of 18 F-fluoroethyl triazole [Tyr 3 ] octreotate ( 18 F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18 F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed wholebody PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18 F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18 F-FET-βAG-TOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent.

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Biodistribution and Radiation Dosimetry of Deuterium-Substituted ¹⁸F-Fluoromethyl-[1, 2-²H₄]Choline in Healthy Volunteers

Cited by 25 publications

References 28 publications

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Metabolic Imaging of Pancreatic Ductal Adenocarcinoma Detects Altered Choline Metabolism

Clinical Translation of a Click-Labeled ¹⁸F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

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Biodistribution and Radiation Dosimetry of Deuterium-Substituted 18F-Fluoromethyl-[1, 2-2H4]Choline in Healthy Volunteers

Cited by 25 publications

References 28 publications

Quantification of 18F-Fluorocholine Kinetics in Patients with Prostate Cancer

Quantification of 18F-Fluorocholine Kinetics in Patients with Prostate Cancer

Metabolic Imaging of Pancreatic Ductal Adenocarcinoma Detects Altered Choline Metabolism

Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors

Contact Info

Product

Resources

About

Biodistribution and Radiation Dosimetry of Deuterium-Substituted ¹⁸F-Fluoromethyl-[1, 2-²H₄]Choline in Healthy Volunteers

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Quantification of ¹⁸F-Fluorocholine Kinetics in Patients with Prostate Cancer

Clinical Translation of a Click-Labeled ¹⁸F-Octreotate Radioligand for Imaging Neuroendocrine Tumors