Abstract

BackgroundSeveral scan parameters for PET imaging with 18F-PSMA-11 such as dosage, acquisition time and scan duration were evaluated to determine the most appropriate scan protocol, as well as the effect of furosemide administration on lesion visualization. Forty-four patients were randomly assigned to a dosage group (2.0 ± 0.2 or 4.0 ± 0.4 MBq/kg 18F-PSMA-11). All patients received a full-body PET/CT 1 h and 3 h after radiotracer injection with a scan duration of 3 min/bed position. For comparison of the scan duration, images were reconstructed for 1.5 and 3 min/bed position. Patients were intravenously administered 0.5 mg/kg furosemide with a maximum dose of 40 mg. To evaluate the furosemide effect, 22 additional patients were recruited and received one full-body PET/CT 1 h after administration of 2.0 ± 0.2 MBq/kg 18F-PSMA-11 with a scan duration of 3 min/bed position. To this group, no furosemide was administered. Images were scored on image quality using a 7-point scale and each suspicious lesion was described. To assess interrater reliability, two nuclear physicians scored all scans independently and described all observed suspicious lesions.ResultsThe 4 MBq/kg group received for all reconstructed images (60 min p.i., 1.5 and 3 min/bed position and 180 min p.i., 1.5 and 3 min/bed position) the highest median image quality score compared to the 2 MBq/kg group (p values < 0.01). When comparing all reconstructed images, the highest image quality score was given to images at 60 min p.i., 3 min/bed position for both dosage groups (score 5 and 6 for 2 and 4 MBq/kg, respectively). The addition of furosemide administration decreased the interference score with one point (p = 0.01106) and facilitated the evaluation of lesions in proximity to the ureters. The interrater reliability for the comparison of each lesion separately after more than 40 18F-PSMA-11 scan readings showed an increasing κ value from 0.78 (95% CI, 0.65–0.92) to 0.94 (95% CI, 0.87–1).ConclusionAlthough the results indicate an administered activity of 4.0 ± 0.4 MBq/kg, preference will be given to 2.0 ± 0.2 MBq/kg due to the small difference in absolute score (max 1 point) and the ALARA principle. For evaluation of lesions in proximity to the ureters, the co-administration of a diuretic can be useful. The increase of the κ value from 0.78 to 0.94 suggests a learning curve in the interpretation of 18F-PSMA-11 images.Trial registrationClinicaltrials.gov, NCT03573011. Retrospectively registered 28 June 2018

Highlights

  • In recent years, prostate-specific membrane antigen (PSMA) has been the most widely studied target for imaging of recurrent and metastatic prostate cancer. 18FPSMA-11, a fluorine-18 derivative of the frequently used 68Ga-PSMA-11 PET radiotracer, was developed [1, 2], automatized [3] and evaluated for safety, biodistribution and dosimetry in a previously published study [4]

  • Before comparing the clinical efficacy of 18F-PSMA-11 to other PSMA tracers, a Phase 2 trial should be conducted to determine the scan protocol which will be applied in following studies and clinical practice

  • The variability between observers should be evaluated as the correct interpretation of PET images is a crucial step in the validation of the clinical efficacy of 18F-PSMA-11 and should lead to the development of criteria for image evaluation

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Summary

Introduction

Prostate-specific membrane antigen (PSMA) has been the most widely studied target for imaging of recurrent and metastatic prostate cancer. 18FPSMA-11, a fluorine-18 derivative of the frequently used 68Ga-PSMA-11 PET radiotracer, was developed [1, 2], automatized [3] and evaluated for safety, biodistribution and dosimetry in a previously published study [4]. Phase 2 trial designs are usually exploratory where multiple scan parameters are tested to determine the optimal scan protocol These parameters include radiotracer dosage, start of PET acquisition post injection, scan duration, image reconstruction parameters and updating the safety database. To evaluate the furosemide effect, 22 additional patients were recruited and received one full-body PET/CT 1 h after administration of 2.0 ± 0.2 MBq/kg 18F-PSMA-11 with a scan duration of 3 min/bed position. To this group, no furosemide was administered. Two nuclear physicians scored all scans independently and described all observed suspicious lesions

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