Dataset Information

External Validation of Two Nomograms Developed for ⁶⁸Ga-PSMA-11 Applied to the Prostate-specific Membrane Antigen Tracer ¹⁸F-DCFPyl: Is Prediction of the Optimal Timing of Salvage Therapy Feasible?

ABSTRACT: Two nomograms have been developed to predict the outcome of positron emission tomography (PET)/computed tomography (CT) imaging with⁶⁸Ga-labeled ligands for prostate-specific membrane antigen (⁶⁸Ga-PSMA) for patients with rising prostate-specific antigen after radical prostatectomy (RP). These nomograms quantify the ability of PSMA PET/CT to detect prostate cancer recurrences, and therefore provide critical information in determining the optimal timing for PSMA PET/CT in guiding salvage therapies. We validated the ability of these nomograms to accurately predict PET/CT outcome using another ligand tracer, ¹⁸F-DCFPyL. The external validation cohort consisted of 157 men from the Prostate Cancer Network Netherlands who underwent ¹⁸F-DCFPyL PET/CT to guide salvage therapies after RP. The nomogram of Rauscher et al (predicting a positive scan) showed accurate prediction of 50-80% (discrimination 0.68, 95% confidence interval [CI] 0.59-0.76). The nomogram of Luiting et al (predicting recurrence outside the prostatic fossa) showed accurate prediction for predicted probability values between 15% and 65%, with a small degree of overestimation for predicted probability values between 30% and 50% (discrimination 0.74, 95% CI 0.28-1.24). According to calibration curves, discrimination results, and decision curve analysis, we conclude that clinicians can use these ⁶⁸Ga-PSMA-based nomograms to predict ¹⁸F-DCFPyL PET/CT outcome. These nomograms improve shared decision-making in determining the optimal time to initiate PSMA PET/CT-guided salvage therapies.

Patient summary

Prediction tools developed for prostate scans (positron emission tomography, PET) using one type of radioactive tracer (chemicals labeled with gallium-68) are also accurate in predicting scan findings with another tracer (a chemical labeled with fluorine-18). Our study confirms that these tools can be used to guide decisions on the timing of treatments for prostate cancer recurrence.

SUBMITTER: Luiting HB

PROVIDER: S-EPMC8317859 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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External Validation of Two Nomograms Developed for 68Ga-PSMA-11 Applied to the Prostate-specific Membrane Antigen Tracer 18F-DCFPyl: Is Prediction of the Optimal Timing of Salvage Therapy Feasible?

Luiting Henk B HB Remmers Sebastiaan S Meijer Dennie D Vis André N AN Donswijk Maarten M Oprea-Lager Daniela E DE Emmett Louise L Rauscher Isabel I Van der Poel Henk G HG Roobol Monique J MJ van Leeuwen Pim J PJ

European urology open science 20210429

Two nomograms have been developed to predict the outcome of positron emission tomography (PET)/computed tomography (CT) imaging with68Ga-labeled ligands for prostate-specific membrane antigen (68Ga-PSMA) for patients with rising prostate-specific antigen after radical prostatectomy (RP). These nomograms quantify the ability of PSMA PET/CT to detect prostate cancer recurrences, and therefore provide critical information in determining the optimal timing for PSMA PET/CT in gu ...[more]

PMID: 34337525

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Project description:PurposeDetailed data comparing the biodistribution of PSMA radioligands is still scarce, raising concerns regarding the comparability of different compounds. We investigated differences in normal-organ biodistribution and uptake variability between the two most commonly PSMA tracers in clinical use, 68Ga-PSMA-11 and 18F-DCFPyL.MethodsThis retrospective analysis included 34 patients with low tumor burden referred for PET/CT imaging with 68Ga-PSMA-11 and subsequently 18F-DCFPyL. Images were acquired with 4 cross-calibrated PET/CT systems. Volumes of interest were placed on major salivary and lacrimal glands, liver, spleen, duodenum, kidneys, bladder, blood-pool and muscle. Normal-organ biodistribution of both tracers was then quantified as SUVpeak and compared using paired tests, linear regression and Bland-Altman analysis. Between-patient variability was also assessed. Clinical and protocol variables were investigated for possible interference.ResultsFor both tracers the highest uptake was found in the kidneys and bladder and low background activity was noted across all scans. In the quantitative analysis there was significantly higher uptake of 68Ga-PSMA-11 in the kidneys, spleen and major salivary glands (p < 0.001), while the liver exhibited slightly higher 18F-DCFPyL uptake (p = 0.001, mean bias 0.79 ± 1.30). The lowest solid-organ uptake variability was found in the liver (COV 21.9% for 68Ga-PSMA-11, 22.5% for 18F-DCFPyL). There was a weak correlation between 18F-DCFPyL uptake time and liver SUVpeak (r = 0.488, p = 0.003) and, accordingly, patients scanned at later time-points had a larger mean bias between the two tracers' liver uptake values (0.05 vs 1.46, p = 0.001).ConclusionNormal tissue biodistribution patterns of 68Ga-PSMA-11 and 18F-DCFPyL were similar, despite subtle differences in quantitative values. Liver uptake showed an acceptable intra-patient agreement and low inter-patient variability between the two tracers, allowing its use as a reference organ for thresholding scans in the qualitative comparison of PSMA expression using these different tracers.

Project description:Prostate-specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68 Ga-PSMA-11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68 Ga-PSMA-11 PET was prospectively performed in patients with treatment-naïve HCC on a digital PET scanner using cyclotron-produced 68 Ga. Uptake was graded qualitatively and semi-quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor-associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10-5 ) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = -0.753; P = 1.58 × 10-6 ). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68 Ga-PSMA-11 standardized uptake value: SUVmax (median [range] 9.2 [4.9-28.4]), SUVmean 4.7 (2.4-12.7), and tumor-to-liver background ratio 2 (1.1-11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68 Ga-PSMA-11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.

Project description:BackgroundRoutine prostate-specific membrane antigen (PSMA) positron emission tomography (PET) performed for primary staging or restaging of prostate cancer patients is usually done as a single static image acquisition 60 min after tracer administration. In this study, we employ dynamic whole-body (D-WB) PET imaging to compare the pharmacokinetics of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 in various tissues and lesions, and to assess whether Patlak parametric images are quantitative and improve lesion detection and image readability.MethodsTwenty male patients with prostate cancer were examined using a D-WB PSMA PET protocol. Ten patients were scanned with [68Ga]Ga-PSMA-11 and ten with [18F]PSMA-1007. Kinetic analyses were made using time-activity curves (TACs) extracted from organs (liver, spleen, bone, and muscle) and lesions. For each patient, three images were produced: SUV + Patlak parametric images (Ki and DV). All images were reviewed visually to compare lesion detection, image readability was quantified using target-to-background ratios (TBR), and Ki and DV values were compared.ResultsThe two PSMA tracers exhibited markedly different pharmacokinetics in organs: reversible for [68Ga]Ga-PSMA-11 and irreversible for [18F]PSMA-1007. For both tracers, lesions kinetics were best described by an irreversible model. All parametric images were of good visual quality using both radiotracers. In general, Ki images were characterized by reduced vascular signal and increased lesion TBR compared with SUV images. No additional malignant lesions were identified on the parametric images.ConclusionD-WB PET/CT is feasible for both PSMA tracers allowing for direct reconstruction of parametric Ki images. The use of multiparametric PSMA images increased TBR but did not lead to the detection of more lesions. For quantitative whole-body Ki imaging, [18F]PSMA-1007 should be preferred over [68Ga]Ga-PSMA-11 due to its irreversible kinetics in organs and lesions.

Project description:PurposeProstate-specific membrane antigen (PSMA) agents, such as [68Ga]Ga-PSMA-11, have an unprecedented accuracy in staging prostate cancer (PCa) and detecting disease recurrence. PSMA PET/CT may also be used for response monitoring by displaying molecular changes, instead of morphological changes alone. However, there are still limited data available on the variability in biodistribution and intra-prostatic uptake of PSMA targeting radiotracers. Therefore, the aim of this study was to assess the repeatability of [68Ga]Ga-PSMA-11 uptake in primary PCa patients in a 4-week interval.MethodsTwenty-four primary PCa patients were prospectively included, who already were scheduled for [68Ga]Ga-PSMA-11 PET/CT scan on clinical indication (≥ cT3, Gleason score ≥ 7 or PSA ≥ 20 ng/mL). These patients received two [68Ga]Ga-PSMA-11 PET/CT scans with a 4-week interval. No treatment was started in between the scans. Semiquantitative measurements (SULmax, SULmean, and SULpeak) were determined in the prostate tumor, normal tissues, and blood pool. The repeatability coefficient of every region was determined. All scans were visually analyzed by two nuclear medicine physicians.ResultsWithin-subject coefficient of variation of [68Ga]Ga-PSMA-11 uptake between the two scans was on average 10% in the prostate tumor, normal tissues (liver, kidney, parotid), and blood pool. The repeatability coefficient of the prostate tumor was 18% for SULpeak and 22% for SULmax. Lesion uptake was visually different in 5 patients, though not clinically relevant.ConclusionResults of test-retest [68Ga]Ga-PSMA-11 PET/CT scans in a 4-week interval show that [68Ga]Ga-PSMA-11 uptake is repeatable, with a clinical irrelevant variation in tumor and physiological distribution. Based on the presented repeatable uptake, [68Ga]Ga-PSMA-11 PET/CT scans can potentially be used for disease surveillance and therapy response monitoring. Changes in uptake larger than the RC are therefore likely to reflect actual biological changes in PSMA expression. Trial registration NL8263 at Trialregister.nl retrospectively registered on 03-01-2020. https://www.trialregister.nl/trial/8263.

Dataset Information

External Validation of Two Nomograms Developed for ⁶⁸Ga-PSMA-11 Applied to the Prostate-specific Membrane Antigen Tracer ¹⁸F-DCFPyl: Is Prediction of the Optimal Timing of Salvage Therapy Feasible?

Patient summary

Publications

External Validation of Two Nomograms Developed for <sup>68</sup>Ga-PSMA-11 Applied to the Prostate-specific Membrane Antigen Tracer <sup>18</sup>F-DCFPyl: Is Prediction of the Optimal Timing of Salvage Therapy Feasible?

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