Examine design and participant choice
This potential, non-randomized, single-center, open-label feasibility examine enrolled 40 sufferers exhibiting BCR following prostatectomy. BCR was outlined as a postoperative PSA focus > 0.2 ng/mL on at the least two events, together with one check carried out inside 1 month previous to offering consent to take part. All sufferers underwent customary imaging exams reminiscent of abdominopelvic CT and bone scans to verify the absence of metastatic lesions. To guage the correlations between recurrent lesion detection charges and serum PSA concentrations30, the sufferers had been stratified into three teams based mostly on their serum PSA concentrations at screening: PSA > 0.2 ng/mL however ≤ 0.5 ng/mL; PSA > 0.5 ng/mL however ≤ 1 ng/mL; and PSA > 1.0 ng/mL.
Upon enrollment, sufferers had been slated to bear analog and digital PET/CT scanning after intravenous injection of [68Ga]Ga-PSMA-11. Two nuclear physicians with information of the affected person’s scientific historical past and former picture outcomes reported the consensus imaging findings to the referring doctor. Sufferers had been clinically adopted up for at the least 6 months by further imaging modalities, together with CT, magnetic resonance imaging (MRI), and bone scan, in accordance with customary tips. Primarily based on these scientific evaluations, sufferers underwent biopsy/surgical procedure, localized radiation remedy, hormonal remedy, or mixture remedy, as wanted, with serum PSA measured at the least each 6 months. On the ultimate scientific follow-up, the PET/CT findings had been evaluated utilizing a composite customary of fact, together with the outcomes of histologic examinations, different imaging findings, and responses to remedy. Publish hoc analyses performed by blinded readers with out entry to scientific info had been deliberate to check the diagnostic performances of [68Ga]Ga-PSMA-11 PET/CT photographs obtained by analog and digital scanners.
This examine was authorised by the Institutional Assessment Board (IRB) at Asan Medical Heart (no. 2021-0195), and all strategies had been carried out in accordance with the related tips and laws. Knowledgeable consent was obtained from all sufferers. The examine protocol was registered at ClinicalTrials.gov (registration no. NCT04846894), and the primary registration was accomplished on 15/04/2021 (registration no. PSMA-S-04).
Preparation of [68Ga]Ga-PSMA-11 and PET/CT imaging
The manufacturing of [68Ga]Ga-PSMA-11 adhered to the authorised as hospital compounding drug, as sanctioned by the regional public well being middle on the establishment’s nuclear medication division. All high quality management procedures are carried out in accordance with European Pharmacopeia. [68Ga]Ga-PSMA-11 was ready by eluting 3 mL of 68GaCl3 from a 68Ge/68Ga generator (iThemba Labs, South-Africa) utilizing 0.6N HCl resolution. Subsequently, 40 μg (42.2 nmol) of PSMA-11 and 1 mL of HEPES buffer advanced resolution (1 M HEPES buffer and NaOH combination) had been added to the GaCl3 resolution, which was heated for 10 min at 100 °C. Following purification with a C18 SPE cartridge and pass-through a 0.22 μm sterile filter, [68Ga]Ga-PSMA-11 was collected in a sterile vial. Typically, radiochemical yield is > 70% and radiochemical purity just isn’t lower than 95%.
Sufferers had been directed to ingest over 500 mL of water per hour previous to [68Ga]Ga-PSMA-11 PET/CT imaging. After an intravenous injection of 1.8–2.2 MBq/kg [68Ga]Ga-PSMA-11, sufferers had been inspired to drink an extra 500 mL of water inside 30 min. PET/CT photographs had been acquired 60 and 90 min after [68Ga]Ga-PSMA-11 injection utilizing analog (GE Discovery 690; GE Medical Methods, Milwaukee, WI, USA) and digital (Siemens Biograph Imaginative and prescient 600; Siemens Healthcare, Erlangen, Germany) scanners, respectively. Imaging was carried out from the vertex to the higher thigh within the caudocranial route. CT photographs from every scanner had been used to generate an attenuation map and localize the lesion. CT imaging parameters on analog PET/CT included 120 kVp, auto mA, 0.5 rotation time, and three.75 mm slice thickness, whereas CT imaging parameters on digital PET/CT included 120 kVp, Care Dose 4D mA, 0.5 rotation time, and three.00 mm slice thickness. Following CT imaging, PET imaging was carried out in three-dimensional mode with a 500 mm subject of view on each analog and digital scanners and three min of emission per mattress place. Analog PET/CT photographs had been reconstructed utilizing the VPFX-S algorithm, consisting of 4 iterations, 18 subsets, a 4.0 mm subject width at half most, and 192 × 192 matrices; whereas digital PET/CT photographs had been reconstructed utilizing the TrueX algorithm and time-of-flight strategies, consisting of 4 iterations, 5 subsets, a 2.0 mm subject width at half most, and 440 × 440 matrices.
Picture evaluation
PET/CT photographs obtained had been topic to each qualitative and quantitative analyses. Two nuclear medication specialists (D. Y. L. & C. S.), blinded to the scientific findings and different imaging outcomes, independently assessed the [68Ga]Ga-PSMA-11 analog and digital PET/CT photographs utilizing a predetermined report type. The knowledge of detected lesions was assessed using 5-grade scoring system (1—positively adverse, 2—in all probability adverse, 3—probably optimistic, 4—in all probability optimistic, and 5—positively optimistic), and rating of equal or greater than 3 had been thought-about optimistic. In case of discrepancies, a 3rd nuclear medication specialist (Y. Ok.) made the ultimate determination. After that, we measured most standardized uptake values (SUVmax) of the optimistic recurrent lesions. SUVmax was calculated utilizing the formulation: SUV = (tissue radioactivity [Bq]/tissue weight [g])/(complete radioactivity [Bq]/physique weight [g]). Volumes-of-interest (VOIs) had been drawn on the PET, CT, and fusion PET/CT photographs utilizing the syngo.by way of software program bundle (Siemens Healthcare, Erlangen, Germany), with most depth projection (MIP) enabled and three-dimensional show settings (transaxial, coronal, and sagittal). As a reference, the imply SUV (SUVmean) of regular liver was decided in a VOI of about 10 cm3 in the proper lobe of the liver.
Final result and statistical evaluation
Categorical knowledge had been introduced as counts with percentages, and steady knowledge as imply ± customary deviation (SD) or median and interquartile vary (IQR). Initially, optimistic lesion detection charges (patient-based) and variety of lesions (lesion-based) obtained by analog and digital [68Ga]Ga-PSMA-11 PET/CT imaging modalities had been in contrast in all sufferers and within the three subgroups outlined by serum PSA concentrations. Subsequently, a patient-based evaluation utilizing follow-up knowledge was carried out to find out the sensitivity and PPV of [68Ga]Ga-PSMA-11 PET/CT imaging findings. The SUVmax of analog and digital PET/CT scans of optimistic lesions had been subsequently in contrast in relation to complete lesions, serum PSA concentrations, and lesion places utilizing Wilcoxon’s signed-rank check. Interrater settlement between the 2 interpreters based mostly on serum PSA degree was in contrast utilizing Cohen’s weighted kappa (κ) indices. A p-value lower than 0.05 was thought-about statistically important. All statistical analyses had been carried out utilizing SPSS software program (Model 18.0; SPSS Inc., Chicago, IL, USA) and MedCalc (Model 20.218; MedCalc Inc., Mariakerke, Belgium).
