Diagnosing small bowel carcinoid tumor in a patient with oligometastatic prostate cancer imaged with PSMA-Targeted [18F]DCFPyL PET/CT: Value of the PSMA-RADS-3D Designation.
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ABSTRACT:
SUBMITTER: Shenderov E
PROVIDER: S-EPMC5849869 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
Publications
Diagnosing small bowel carcinoid tumor in a patient with oligometastatic prostate cancer imaged with PSMA-Targeted [<sup>18</sup>F]DCFPyL PET/CT: Value of the PSMA-RADS-3D Designation.
Shenderov Eugene E Gorin Michael A MA Kim Seohyun S Johnson Pamela T PT Allaf Mohamad E ME Partin Alan W AW Pomper Martin G MG Antonarakis Emmanuel S ES Pienta Kenneth J KJ Rowe Steven P SP
Urology case reports 20171219
Radiotracers targeting prostate-specific membrane antigen (PSMA), including [<sup>18</sup>F]DCFPyL, have been extensively investigated as a means to image prostate cancer more accurately. We present the case of a man with oligometastatic prostate cancer who was also diagnosed with a metastatic small bowel carcinoid tumor following the detection of indeterminate findings on a [<sup>18</sup>F]DCFPyL PET and discuss how this case highlights the utility of a newly proposed reporting system for PSMA- ...[more]
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Project description:We present the case of a man with oligometastatic prostate cancer who underwent a PSMA-targeted 18F-DCFPyL PET/CT scan in order to illustrate how the PSMA-RADS grading sytem can be successfully used to support clinical decision-making and treatment planning. Notably, the presented patient was found to have an equivocal bone lesion (PSMA-RADS-3B) which was further worked up with a tumor protocol MRI and found to be definitively benign (PSMA-RADS-1B) and thus removed from the oligometastatic treatment plan. Remaining avid lesions were incorporated into the treatment plan or deferred for later work-up or monitoring, as indicated within the PSMA-RADS framework.
| S-EPMC6348696 | biostudies-literature
Project description:BACKGROUND:Due to its high and consistent expression in prostate cancer (PCa), the prostate-specific membrane antigen (PSMA) represents an ideal target for molecular imaging and targeted therapy using highly specific radiolabeled PSMA ligands. To address the continuously growing clinical demand for 18F-labeled PSMA-probes, we developed two novel Glu-urea-Glu-(EuE)-based inhibitors, EuE-k-18F-FBOA (1) and EuE-k-?-a-18F-FPyl (2), both with optimized linker structure and different 18F-labeled aromatic moieties. The inhibitors were evaluated in a comparative preclinical study with 18F-DCFPyl and 18F-PSMA-1007. RESULTS:Radiolabeling procedures allowed preparation of (1) and (2) with high radiochemical yields (67?±?7 and 53?±?7%, d.c.) and purity (>?98%). When compared with 18F-DCFPyl (IC50 = 12.3?±?1.2 nM) and 18F-PSMA-1007 (IC50 = 4.2?±?0.5 nM), both metabolically stable EuE-based ligands showed commensurable or higher PSMA affinity (IC50 = 4.2?±?0.4 nM (1), IC50 = 1.1?±?0.2 nM (2)). Moreover, 1.4- and 2.7-fold higher internalization rates were observed for (1) and (2), respectively, resulting in markedly enhanced tumor accumulation in LNCaP-tumor-bearing mice ((1) 12.7?±?2.0% IA/g, (2) 13.0°?±?1.0% IA/g vs. 7.3?±?1.0% IA/g (18F-DCFPyl), 7.1?±?1.5% IA/g (18F-PSMA-1007), 1 h p.i.). In contrast to (1), (2) showed higher kidney accumulation and delayed clearance kinetics. Due to the high hydrophilicity of both compounds, almost no unspecific uptake in non-target tissue was observed. In contrast, due to the less hydrophilic character (logP?=?-?1.6) and high plasma protein binding (98%), 18F-PSMA-1007 showed uptake in non-target tissue and predominantly hepatobiliary excretion, whereas, 18F-DCFPyl exhibited pharmacokinetics quite similar to those obtained with (1) and (2). CONCLUSION:Both 18F-labeled EuE-based PSMA ligands showed excellent in vitro and in vivo PSMA-targeting characteristics. The substantially higher tumor accumulation in mice compared to recently introduced 18F-PSMA-1007 and 18F-DCFPyl suggests their high value for preclinical studies investigating the effects on PSMA-expression. In contrast to (2), (1) seems to be more promising for further investigation, due to the more reliable 18F-labeling procedure, the faster clearance kinetics with comparable high tumor uptake, resulting therefore in better high-contrast microPET imaging as early as 1 h p.i.
| S-EPMC5897267 | biostudies-literature
Project description:Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted PET imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET examinations in a prospective setting mimicking the typical clinical workflow at a prostate cancer referral center. Methods: Four readers (2 experienced readers (ERs, >3 y of PSMA-targeted PET interpretation experience) and 2 inexperienced readers (IRs, <1 y of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/CT studies independently. Per scan, a maximum of 5 target lesions was selected by the observers, and a PSMA-RADS score for every target lesion was recorded. No specific preexisting conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated, and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed. Results: The number of target lesions identified by each observer was as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least 2 individual observers (all 4 readers selected the same target lesion in 58 of 125 [46.4%] instances, 3 readers in 40 of 125 [32%], and 2 observers in 27 of 125 [21.6%]). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient [ICC] for 4, 3, and 2 identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC, 0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC, 0.84), with a significant difference for ER (ICC, 0.97) vs. IR (ICC, 0.74) (P = 0.005). Conclusion: PSMA-RADS demonstrated a high concordance rate in this study, even among readers with different levels of experience. This finding suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.
| S-EPMC6278904 | biostudies-literature
Project description:ObjectiveComplete surgical resection of metastatic sites has been shown to prolong survival in select patients with oligometastatic RCC. This treatment strategy is dependent upon the accurate characterization of a patient's extent of disease. The objective of this study was to explore the utility of PSMA-targeted 18F-DCFPyL PET/CT in patients with presumed oligometastatic clear cell RCC.MethodsThis is a subset analysis of a prospective study in which patients with RCC were imaged with 18F-DCFPyL PET/CT (ClinicalTrials.gov identifier NCT02687139). In the present analysis, patients with oligometastatic clear cell RCC, defined as ≤ 3 metastatic lesions on conventional imaging, were evaluated. 18F-DCFPyL PET/CT scans were reviewed for sites of disease and compared to conventional imaging.ResultsThe final cohort included 14 patients with oligometastatic clear cell RCC. Conventional imaging revealed 21 metastatic lesions and 3 primary tumors. 18F-DCFPyL PET/CT detected 29 sites of metastatic disease and 3 primary tumors. Of the 21 metastatic lesions detected on conventional imaging, 17 (81.0%) had radiotracer uptake. Additionally, all 3 primary tumors had radiotracer uptake. In 4 (28.6%) patients a total of 12 more lesions were identified on 18F-DCFPyL PET/CT than conventional imaging. Notably, 3 (21.4%) patients were no longer considered oligometastatic. The detection rates of conventional imaging and 18F-DCFPyL PET/CT for identifying sites of disease were 66.7% and 88.9%, respectively.ConclusionsPSMA-targeted PET/CT appears to aid in the identification of patients with oligometastatic clear cell RCC. If borne out in future studies, this suggests that PSMA-targeted imaging has the potential to help select candidates for metastasis-directed therapy.
| S-EPMC9774684 | biostudies-literature
Project description:BACKGROUND:Recent studies reported on high uptake of the PSMA ligands [68Ga]HBED-CC (68Ga-PSMA) and 18F-DCFPyL in cerebral gliomas. This study explores the regional uptake and cellular targets of 68Ga-PSMA and 18F-DCFPyL in three different rat glioma models. METHODS:F98, 9 L, or U87 rat gliomas were implanted into the brains of 38 rats. After 13 days of tumor growth, 68Ga-PSMA (n = 21) or 18F-DCFPyL (n = 17) was injected intravenously, and animals were sacrificed 40 min later. Five animals for each tracer and tumor model were additionally investigated by micro-PET at 20-40 min post injection. Cryosections of the tumor bearing brains were analyzed by ex vivo autoradiography and immunofluorescence staining for blood vessels, microglia, astrocytes, and presence of PSMA. Blood-brain barrier (BBB) permeability was tested by coinjection of Evans blue dye (EBD). 68Ga-PSMA uptake after restoration of BBB integrity by treatment with dexamethasone (Dex) was evaluated in four animals with U87 gliomas. Competition experiments using the PSMA-receptor inhibitor 2-(phosphonomethyl)pentane-1,5-dioic acid (PMPA) were performed for both tracers in two animals each. RESULTS:Autoradiography demonstrated a strong 68Ga-PSMA and 18F-DCFPyL binding in the peritumoral area and moderate binding in the center of the tumors. PMPA administration led to complete inhibition of 68Ga-PSMA and 18F-DCFPyL binding in the peritumoral region. Restoration of BBB by Dex treatment reduced EBD extravasation but 68Ga-PSMA binding remained unchanged. Expression of activated microglia (CD11b) was low in the intra- and peritumoral area but GFAP staining revealed strong activation of astrocytes in congruency to the tracer binding in the peritumoral area. All tumors were visualized in micro PET, showing a lower tumor/brain contrast with 68Ga-PSMA than with 18F-DCFPyL. CONCLUSIONS:High uptake of 68Ga-PSMA and 18F-DCFPyL in the peritumoral area of all glioma models is presumably caused by activated astrocytes. This may represent a limitation for the clinical application of PSMA ligands in gliomas.
| S-EPMC7378136 | biostudies-literature
Project description:We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [(18)F]DCFPyL, as a potential imaging agent for the prostate-specific membrane antigen (PSMA). PSMA is upregulated in prostate cancer epithelia and in the neovasculature of most solid tumors.[(18)F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[(18)F]fluoronicotinic acid tetrafluorophenyl ester ([(18)F]F-Py-TFP) for introduction of (18)F. Radiochemical synthesis was followed by biodistribution and imaging with PET in immunocompromised mice using isogenic PSMA PC3 PIP and PSMA- PC3 flu xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0.DCFPyL displays a K(i) value of 1.1 ± 0.1 nmol/L for PSMA. [(18)F]DCFPyL was produced in radiochemical yields of 36%-53% (decay corrected) and specific radioactivities of 340-480 Ci/mmol (12.6-17.8 GBq/?mol, n = 3). In an immunocompromised mouse model [(18)F]DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 hours postinjection, 39.4 ± 5.4 percent injected dose per gram of tissue (%ID/g) was evident within the PSMA+ PC3 PIP tumor, with a ratio of 358:1 of uptake within PSMA+ PC3 PIP to PSMA- PC3 flu tumor placed in the opposite flank. At or after 1 hour postinjection, minimal nontarget tissue uptake of [(18)F]DCFPyL was observed. The bladder wall is the dose-limiting organ.These data suggest [(18)F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues.
| S-EPMC3243762 | biostudies-literature
Project description:IntroductionClinical and biochemical assessment and biopsies can miss clinically significant prostate cancers (csPCa) in up to 20% of patients and diagnose clinically insignificant tumours leading to overtreatment. This retrospective study analyses the accuracy of 18 F-DCFPyL PET/CT in detecting csPCa as a primary diagnostic tool and directly compares it with mpMRI prostate in treatment-naive patients. The two modalities are then correlated to determine whether they are better in combination, than either alone.MethodsThis is a retrospective dual-institution study of patients who underwent contemporaneous MRI and PSMA-PET between January 2017 and March 2020 with histologic confirmation. The images were re-reviewed and concordance between modalities assessed. Results were compared with histopathology to determine the ability of MRI and PSMA-PET to detect csPCA.ResultsMRI and PSMA-PET detected the same index lesion in 90.8% of cases with a kappa of 0.82. PET detected an additional 6.2% of index lesions which were MRI occult. MRI detected an additional 3.1% which were PET occult. No additional csPCa was identified on pathology which was not seen on imaging. The sensitivity of PSMA-PET in detecting csPCa is 96.7% and that of MRI is 93.4% with no statistically significant difference between the two (P = 0.232). Both modalities detected all four cases of non-csPCa with these being considered false positives.ConclusionBoth mpMRI and 18F-DCFPyL-PSMA-PET/CT have high sensitivity for detecting csPCa with high agreement between modalities. There were no synchronous csPCa lesions detected on pathology that were not detected on imaging too.
| S-EPMC9790525 | biostudies-literature
Project description:Prostate-specific membrane antigen (PSMA)-targeted PET imaging has become commonly used in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft-tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa. Methods: PET/CT imaging with 18F-DCFPyL was performed in 110 patients with PCa, and lesions were categorized according to PSMA-RADS version 1.0. The study reported herein is a retrospective analysis of those patients. Fifty-six of 110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions, and 22 of 56 (39.3%) patients had adequate follow-up to be included in the analysis (median follow-up time was 10 mo [range, 3-22 mo]). The SUVmax of the lesions was obtained, and the ratios of SUVmax of the lesions to SUVmean of blood pool (SUVmax-lesion/SUVmean-bloodpool) were calculated. Predetermined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine whether they demonstrated evidence of underlying malignancy. Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e., PSMA-RADS-3A [32 lesions] or PSMA-RADS-3B [14 lesions]) and were evaluable on follow-up imaging. Twenty-seven of 46 (58.7%) lesions demonstrated changes suggesting they were true-positive for PCa. These lesions included 24 of 32 (75.0%) PSMA-RADS-3A lesions and 3 of 14 (21.4%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up. The presence of additional definitive sites of PCa (PSMA-RADS-4 and PSMA-RADS-5) increases the likelihood that indeterminate lesions will manifest as true-positive on follow-up imaging. Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa, and this information should be considered when guiding patient therapy.
| S-EPMC6448464 | biostudies-literature
Project description:PurposeTo assess the outcome of radiotherapy (RT) to all PSMA ligand positive metastases for patients with castrate-resistant prostate cancer (mCRPC).Patients and methodsA total of 42 patients developed oligometastatic mCRPC and received PSMA PET-guided RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS), and second-line systemic treatment free survival (SST-FS).ResultsA total of 141 PSMA ligand-positive metastases were irradiated. The median follow-up time was 39.0 months (12-58 months). During the follow-up five out of 42 (11.9%) patients died of progressive mPCa. Five out of 42 (11.9%) patients showed no biochemical responses and presented with a PSA level ≥10% of the baseline PSA at first PSA level measurement after RT and were classified as non-responders. The median PSA level before RT was 4.79 ng/mL (range, 0.4-46.1), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range, <0.07-32.8; p=0.002). The median PSA level at biochemical progression after PSMA ligand-based RT was 2.75 ng/mL (range, 0.27-53.0; p=0.24) and was not significantly different (p=0.29) from the median PSA level (4.79 ng/mL, range, 0.4-46.1) before the PSMA ligand-based RT. The median bPFS was 12.0 months after PSMA ligand PET-based RT (95% CI, 11.2-15.8) and the median SST-FS was 15.0 months (95% CI, 14.0-21.5).ConclusionIn well-informed and closely followed-up patients, PSMA PET-guided RT represents a viable treatment option for patients with oligometastatic mCRPC to delay further systemic therapies.
| S-EPMC8089391 | biostudies-literature
Project description:Theranostics, a combination of therapy and diagnostics, is a field of personalized medicine involving the use of the same or similar radiopharmaceutical agents for the diagnosis and treatment of patients. Prostate-specific membrane antigen (PSMA) is a promising theranostic target for the treatment of prostate cancers. Diagnostic PSMA radiopharmaceuticals are currently used for staging and diagnosis of prostate cancers, and imaging can predict response to therapeutic PSMA radiopharmaceuticals. While mainly used in the setting of metastatic, castrate-resistant disease, clinical trials are investigating the use of PSMA-based therapy at earlier stages, including in hormone-sensitive or hormone-naïve prostate cancers, and in oligometastatic prostate cancers. This review explores the use of PSMA as a theranostic target and investigates the potential use of PSMA in earlier stage disease, including hormone-sensitive metastatic prostate cancer, and oligometastatic prostate cancer.
| S-EPMC8621856 | biostudies-literature