(S)-4-(3-¹⁸F-Fluoropropyl)-l-Glutamic Acid: An ¹⁸F-Labeled Tumor-Specific Probe for PET/CT Imaging—Dosimetry

Abstract

The glutamic acid derivative (S)-4-(3-18 F-Fluoropropyl)-L-glutamic acid ( 18 F-FSPG, alias BAY 94-9392), a new PET tracer for the detection of malignant diseases, displayed promising results in non-small cell lung cancer patients. The aim of this study was to provide dosimetry estimates for 18 F-FSPG based on human whole-body PET/CT measurements. Methods: 18 F-FSPG was prepared by a fully automated 2-step procedure and purified by a solid-phase extraction method. PET/CT scans were obtained for 5 healthy volunteers (mean age, 59 y; age range, 51-64 y; 2 men, 3 women). Human subjects were imaged for up to 240 min using a PET/CT scanner after intravenous injection of 299 6 22.5 MBq of 18 F-FSPG. Image quantification, timeactivity data modeling, estimation of normalized number of disintegrations, and production of dosimetry estimates were performed using the RADAR (RAdiation Dose Assessment Resource) method for internal dosimetry and in general concordance with the methodology and principles as presented in the MIRD 16 document. Results: Because of the renal excretion of the tracer, the absorbed dose was highest in the urinary bladder wall and kidneys, followed by the pancreas and uterus. The individual organ doses (mSv/MBq) were 0.40 6 0.058 for the urinary bladder wall, 0.11 6 0.011 for the kidneys, 0.077 6 0.020 for the pancreas, and 0.030 6 0.0034 for the uterus. The calculated effective dose was 0.032 6 0.0034 mSv/MBq. Absorbed dose to the bladder and the effective dose can be reduced significantly by frequent bladder-voiding intervals. For a 0.75-h voiding interval, the bladder dose was reduced to 0.10 6 0.012 mSv/MBq, and the effective dose was reduced to 0.015 6 0.0010 mSv/MBq. Conclusion: On the basis of the distribution and biokinetic data, the determined radiation dose for 18 F-FSPG was calculated to be 9.5 6 1.0 mSv at a patient dose of 300 MBq, which is of similar magnitude to that of 18 F-FDG (5.7 mSv). The effective dose can be reduced to 4.5 6 0.30 mSv (at 300 MBq), with a bladder-voiding interval of 0.75 h.

Characterization of Physiologic18F FSPG Uptake in Healthy Volunteers

“…18 F FSPG did not accumulate in inflammatory lesions in animals (3). The first pilot clinical studies to examine dosimetry in healthy volunteers (4) and tumor detection in patients with non-small-cell lung cancer and hepatocellular carcinoma showed promising results (5,6). The purpose of this study was to evaluate the normal biodistribution and kinetics of (S)-4- (3-[18F] inflammatory processes can take up 18 F FDG, thereby causing false-positive interpretations (1).…”

Suggested pathway to assess radiation safety of 18F-labeled PET tracers for first-in-human studies

“…Notably, the dose to the bladder and the gallbladder may be reduced by stimulating voiding. For example, in those studies in which different voiding models were simulated, the equivalent dose to the bladder was reduced by a factor of two to four [4, 15–19]. Voiding of the bladder can be induced by diuretics or simple hydration, while voiding of the gallbladder can be stimulated with cholecystokinin or fatty foods.…”

Impact of interpatient variability on organ dose estimates according to MIRD schema: Uncertainty and variance‐based sensitivity analysis

“…Activity data of a novel radiopharmaceutical 18 F-FSPG designed for positron emission tomography (PET) imaging of malignant diseases were employed in this work. The activity data were initially acquired by Smolarz et al 23 from five healthy volunteers (two men, three women) and used for the development of the compartmental pharmacokinetic models for this agent, as reported elsewhere. 24 The 11 source regions for 18 F-FSPG included kidneys, bladder content, heart, thyroid, salivary glands, pancreas, stomach wall, liver, spleen, rest of body and blood.…”