PSMA-Based [18F]DCFPyL PET/CT Is Superior to Conventional Imaging for Lesion Detection in Patients with Metastatic Prostate Cancer (original) (raw)
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Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2017
The introduction ofF-labelled prostate-specific membrane antigen (PSMA) targeted positron emission tomography/computed-tomography (PET/CT) tracers, firstlyF-DCFPyL and more recentlyF-PSMA-1007, have demonstrated promising results for the diagnostic workup of prostate cancer (PCa). This clinical study presents an intra-individual comparison to evaluate tracer-specific characteristics ofF-DCFPyL versusF-PSMA-1007.Twelve prostate cancer patients, drug naive or prior to surgery, received similar activities of about 250 MBqF-DCFPyL andF-PSMA-1007 48 h apart and were imaged 2 h p.i. in the same PET/CT-scanner using the same reconstruction-algorithm. Normal organ biodistribution and tumor uptakes were quantified using SUVPSMA-positive lesions were detected in twelve out of twelve PCa patients. Both tracers,F-DCFPyL andF-PSMA-1007, detected the identical lesions. No statistical significance could be observed when comparing the SUVofF-DCFPyL andF-PSMA-1007 for local tumor, lymph node metasta...
The Journal of Urology, 2018
, we selected those who performed an early scan for the detection of prostate fossae recurrences and had a PSA levels <2 ng/mL at PET time. 75 subjects met the inclusion criteria. All these patients underwent an early static (after 2 minutes from the FCH injection; 1 bed; 5 minutes/bed) and late whole-body (after 60 minutes from FCH injection; 7 beds; 3 minutes/ bed) PET/CT acquisition. A correlation among terapeutic factors, Gleason Score, PSA levels, PSA doubling time (PSAdt), PSA velocity (PSA vel) and early PET/CT findings were assessed by using the chisquare test and Mann-Whitney test. The agreement between early and late PET/CT acquisitions was studied by K-statistic. ROC analysis was used to evaluate the optimal cutoff point for PSA able to distinguish positive and negative PET/CT finding. A p<0.05 was considered statistically significant. RESULTS: PET/CT showed a pathological tracer uptake in 25 patients (33.3%); in 15 cases confined to the prostatic bed, in 4 to lymph nodes, in 4 to the bone, in 2 to both prostatic fossae and lymph nodes and in 3 to both bone and lymph nodes. Therefore, the detection rate of PET/CT was higher for local recurrences (18/25; 72%). PSA values increased in patients with a positive PET/CT finding compared to subjects with a negative scan. Similarly, PSAdt and PSAvel values were different between patients with a positive and a negative PET/CT scan (6.9 versus 10.2 mo and 0.6 versus 0.4 ng/mL/year, respectively). 15 patients had positive early scans and only 4/15 were positive for both early and late PET/CT acquisition (Kappa value ¼ 0.368; p< 0.001). No correlation was found between the PSAdt or PSAvel and positive or negative early PET/CT images. At ROC analysis a PSA value of 0.67 ng/mL showed a sensitivity and specificity of 69% and 64%, respectively, to distinguish patients with positive or negative PET findings. Using this cutoff value, FCH PET/CT was positive in 23% of patients with PSA < 0.67 ng/mL; 12% of patients had a positive early PET/CT and therefore 88% had negative early scans. CONCLUSIONS: From this study emerges that, in patients with PSA < 2 ng/mL, local recurrence is more often detect by FCH PET/CT finding. An early PET acquisition is able to improve the detection rate, expecially in prostatic fossae, and we reported in this study that local findings were increased to 70%. Our results suggest that the selection of patients ungergoing a "dual phase" PET/CT should be based not only on PSA value but also on PSA kinetic.
A Prospective Study on 18F-DCFPyL PSMA PET/CT Imaging in Biochemical Recurrence of Prostate Cancer
Journal of Nuclear Medicine
18 F-DCFPyL (2-(3-{1-carboxy-5-[(6-18 F-fluoro-pyridine-3-carbonyl)amino]-pentyl}-ureido)-pentanedioic acid), a prostate-specific membrane antigen-targeting radiotracer, has shown promise as a prostate cancer imaging radiotracer. We evaluated the safety, sensitivity, and impact on patient management of 18 F-DCFPyL in the setting of biochemical recurrence of prostate cancer. Methods: Subjects with prostate cancer and biochemical recurrence after radical prostatectomy or curative-intent radiotherapy were included in this prospective study. The subjects underwent 18 F-DCFPyL PET/CT imaging. The localization and number of lesions were recorded. The uptake characteristics of the 5 most active lesions were measured. A pre-and posttest questionnaire was sent to treating physicians to assess the impact on management. Results: One hundred thirty subjects were evaluated. 18 F-DCFPyL PET/CT localized recurrent prostate cancer in 60% of cases with a prostate-specific antigen
18F-DCFBC PET/CT for PSMA-Based Detection and Characterization of Primary Prostate Cancer
The Journal of Nuclear Medicine, 2015
We previously demonstrated the ability to detect metastatic prostate cancer using N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-18 F-fluorobenzyl-L-cysteine (18 F-DCFBC), a low-molecular-weight radiotracer that targets the prostate-specific membrane antigen (PSMA). PSMA has been shown to be associated with higher Gleason grade and more aggressive disease. An imaging biomarker able to detect clinically significant high-grade primary prostate cancer reliably would address an unmet clinical need by allowing for riskadapted patient management. Methods: We enrolled 13 patients with primary prostate cancer who were imaged with 18 F-DCFBC PET before scheduled prostatectomy, with 12 of these patients also undergoing pelvic prostate MR imaging. Prostate 18 F-DCFBC PET was correlated with MR imaging and histologic and immunohistochemical analysis on a prostate-segment (12 regions) and dominantlesion basis. There were no incidental extraprostatic findings on PET suggestive of metastatic disease. Results: MR imaging was more sensitive than 18 F-DCFBC PET for detection of primary prostate cancer on a per-segment (sensitivities of up to 0.17 and 0.39 for PET and MR imaging, respectively) and per-dominant-lesion analysis (sensitivities of 0.46 and 0.92 for PET and MR imaging, respectively). However, 18 F-DCFBC PET was more specific than MR imaging by per-segment analysis (specificities of 0.96 and 0.89 for PET and MR imaging for corresponding sensitivity, respectively) and specific for detection of high-grade lesions (Gleason 8 and 9) greater than 1.0 mL in size (4/4 of these patients positive by PET). 18 F-DCFBC uptake in tumors was positively correlated with Gleason score (r 5 0.64; PSMA expression, r 5 0.47; and prostate-specific antigen, r 5 0.52). There was significantly lower 18 F-DCFBC uptake in benign prostatic hypertrophy than primary tumors (median maximum standardized uptake value, 2.2 vs. 3.5; P 5 0.004). Conclusion: Although the sensitivity of 18 F-DCFBC for primary prostate cancer was less than MR imaging, 18 F-DCFBC PET was able to detect the more clinically significant high-grade and larger-volume tumors (Gleason score 8 and 9) with higher specificity than MR imaging. In particular, there was relatively low 18 F-DCFBC PET uptake in benign prostatic hypertrophy lesions, compared with cancer in the prostate, which may allow for more specific detection of primary prostate cancer by 18 F-DCFBC PET. This study demonstrates the utility of PSMA-based PET, which may be used in conjunction with MR imaging to identify clinically significant prostate cancer.
18F-DCFBC PET/CT for PSMA-based Detection and Characterization of Primary Prostate Cancer
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
We previously demonstrated the ability to detect metastatic prostate cancer using (18)F-DCFBC (DCFBC), a low-molecular-weight radiotracer that targets the prostate-specific membrane antigen (PSMA). PSMA has been shown to be associated with higher Gleason grade and more aggressive disease. An imaging biomarker able to detect clinically significant high-grade primary prostate cancer reliably would address an unmet clinical need by allowing for risk-adapted patient management. We enrolled 13 patients with primary prostate cancer who were imaged with DCFBC PET prior to scheduled prostatectomy, with 12 of these patients also undergoing pelvic prostate MRI. Prostate DCFBC PET was correlated with MRI and histological and immunohistochemical (IHC) analysis on a prostate segment (12 regions) and dominant lesion basis. There were no incidental extraprostatic findings on PET suspicious for metastatic disease. MRI was more sensitive than DCFBC PET for detection of primary prostate cancer on a p...
The Journal of Nuclear Medicine, 2018
The purpose of this study was to compare the diagnostic performance of 18 F-DCFBC PET/CT, a first-generation 18 F-labeled prostate-specific membrane antigen (PSMA)-targeted agent, and 18 F-NaF PET/CT, a sensitive marker of osteoblastic activity, in a prospective cohort of patients with metastatic prostate cancer. Methods: Twenty-eight prostate cancer patients with metastatic disease on conventional imaging prospectively received up to 4 PET/CT scans. All patients completed baseline 18 F-DCFBC PET/ CT and 18 F-NaF PET/CT scans, and 23 patients completed follow-up imaging, with a median follow-up interval of 5.7 mo (range, 4.2-12.6 mo). Lesion detection was compared across the 2 PET/CT agents at each time point. Detection and SUV characteristics of each PET/CT agent were compared with serum prostate-specific antigen (PSA) levels and treatment status at the time of baseline imaging using nonparametric statistical testing (Spearman correlation, Wilcoxon rank). Results: Twenty-six patients had metastatic disease detected on 18 F-NaF or 18 F-DCFBC at baseline, and 2 patients were negative on both scans. Three patients demonstrated soft tissue-only disease. Of 241 lesions detected at baseline, 56 were soft-tissue lesions identified by 18 F-DCFBC only and 185 bone lesions detected on 18 F-NaF or 18 F-DCFBC. 18 F-NaF detected significantly more bone lesions than 18 F-DCFBC (P , 0.001). Correlation of PSA with patient-level SUV metrics was strong in 18 F-DCFBC (ρ. 0.5, P , 0.01) and poor in 18 F-NaF (ρ , 0.3, P. 0.1). When PSA levels were combined with treatment status, patients with below-median levels of PSA (,2 ng/mL) on androgen deprivation therapy (n 5 11) demonstrated more lesions on 18 F-NaF than 18 F-DCFBC (P 5 0.02). In PSA greater than 2 ng/mL, patients on androgen deprivation therapy (n 5 8) showed equal to or more lesions on 18 F-DCFBC than on 18 F-NaF. Conclusion: The utility of PSMA-targeting imaging in metastatic prostate cancer appears to depend on patient disease course and treatment status. Compared with 18 F-NaF PET/CT, 18 F-DCFBC PET/CT detected significantly fewer bone lesions in the setting of early or metastatic castrate-sensitive disease on treatment. However, in advanced metastatic castrate-resistant prostate cancer, 18 F-DCFBC PET/CT shows good concordance with NaF PET/CT.
Therapy response assessment is a critical step in cancer management, leading clinicians to optimize the use of therapeutic options during the course of the disease. Imaging is a pivotal biomarker for therapy response evaluation in oncology and has gained wider use through the development of reproducible data-based guidelines, of which the Response Evaluation Criteria in Solid Tumors is the most successful example. Disease-specific criteria have also been proposed, and the Prostate Cancer Working Group 3 criteria are the mainstay for prostate cancer (PC). However, conventional imaging evaluation in metastatic prostate cancer has several limitations, including (a) the inability to detect small-volume disease, (b) the high prevalence of bone (nonmeasurable) lesions at imaging, and (c) the established role of serum prostate-specific antigen (PSA) levels as the biomarker of choice for response assessment and disease progression. In addition, there are an increasing number of newer treatment options with various effects on imaging features. Prostate-specific membrane antigen (PSMA) PET has improved patient selection for newer treatments, such as metastasis-directed therapy (MDT) or radionuclide therapy. The role of PSMA PET in response assessment for many metastatic PC therapeutic options (MDT, androgen deprivation therapy, chemotherapy, radionuclide therapy, and immunotherapy) is an evolving issue, with emerging data showing good correlation with PSA levels and clinical outcome. However, there are specific implications of each therapy (especially androgen deprivation therapy and immunotherapy) on PSMA expression by PC cells, leading to potential pitfalls and inaccuracies that must be known by radiologists. Despite some limitations, PSMA PET is addressing gaps left by conventional imaging methods (eg, CT and bone scanning) and nonimaging biomarkers (PSA levels) in metastatic PC therapy response assessment, a role that can be improved with advances like refinement of interpretation criteria and whole-body tumor burden quantification. © RSNA, 2020 • Abbreviations: ADT = androgen deprivation therapy, CRPC = castration-resistant PC, FDG = fluorine 18 fluorodeoxyglucose, ISUP = International Society of Urological Pathology, MDT = metastasis-directed therapy, PC = prostate cancer, PCWG3 = Prostate Cancer Working Group 3, PSA = prostate-specific antigen, PSMA = prostate-specific membrane antigen, RECIST = Response Evaluation Criteria in Solid Tumors, SBRT = stereotactic body radiation therapy, SUV max = maximum standardized uptake value RadioGraphics 2020; 40:0000-0000 https://doi.
Clinical perspectives of PSMA PET/MRI for prostate cancer
Clinics (Sao Paulo, Brazil), 2018
Prostate cancer imaging has become an important diagnostic modality for tumor evaluation. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has been extensively studied, and the results are robust and promising. The advent of the PET/magnetic resonance imaging (MRI) has added morphofunctional information from the standard of reference MRI to highly accurate molecular information from PET. Different PSMA ligands have been used for this purpose including 68gallium and 18fluorine-labeled PET probes, which have particular features including spatial resolution, imaging quality and tracer biodistribution. The use of PSMA PET imaging is well established for evaluating biochemical recurrence, even at low prostate-specific antigen (PSA) levels, but has also shown interesting applications for tumor detection, primary staging, assessment of therapeutic responses and treatment planning. This review will outline the potential role of PSMA PET/MRI for the clinical asses...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2018
The purpose of this study was to compare the diagnostic performance of F-DCFBC positron emission tomography/computed tomography (PET/CT), a first generation F-labelled prostate-specific membrane antigen (PSMA)-targeted agent, and F-NaF PET/CT, a sensitive marker of osteoblastic activity, in a prospective cohort of patients with metastatic prostate cancer. Twenty-eight prostate cancer patients with metastatic disease on conventional imaging prospectively received up to four PET/CT scans. All patients completed baseline F-DCFBC PET/CT and F-NaF PET/CT scans and 23 patients completed follow-up imaging, with median follow-up interval of 5.7 months (range 4.2-12.6 months). Lesion detection was compared across the two PET/CT agents at each timepoint. Detection and standardized uptake value (SUV) characteristics of each PET/CT agent were compared with serum prostate-specific antigen (PSA) levels and treatment status at the time of baseline imaging using non-parametric statistical testing (...
Cancers, 2019
Background: The use of radiolabeled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for biochemical recurrent prostate cancer (BRPCa) is increasing worldwide. Recently, 18F-labeled PSMA agents have become available. We performed a systematic review and meta-analysis regarding the detection rate (DR) of 18F-labeled PSMA PET/CT in BRPCa to provide evidence-based data in this setting. Methods: A comprehensive literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases through 23 April 2019 was performed. Pooled DR was calculated on a per-patient basis, with pooled proportion and 95% confidence interval (95% CI). Furthermore, pooled DR of 18F-PSMA PET/CT using different cut-off values of prostate-specific antigen (PSA) was obtained. Results: Six articles (645 patients) were included in the meta-analysis. The pooled DR of 18F-labeled PSMA PET/CT in BRPCa was 81% (95% CI: 71–88%). The pooled DR was 86% for PSA ≥ 0.5 ng/mL (...