Dataset Information

Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma with PSMA-Targeted [¹⁸F]DCFPyL PET/CT.

ABSTRACT:

Purpose

To investigate the utility of prostate-specific membrane antigen (PSMA)-targeted [¹⁸F]DCFPyL positron emission tomography (PET)/X-ray computed tomography (CT) imaging for the detection of sites of disease in patients with metastatic non-clear cell renal cell carcinoma (RCC).

Procedures

Eight patients with metastatic non-clear cell RCC underwent imaging with PSMA-targeted [¹⁸F]DCFPyL PET/CT. Imaged RCC histologic subtypes included papillary RCC (n = 3), chromophobe RCC (n = 2), unclassified RCC (n = 2), and Xp11 translocation RCC (n = 1). Using comparison to conventional CT and/or magnetic resonance imaging as reference, two radiologists with expertise in nuclear medicine identified putative sites of disease on [¹⁸F]DCFPyL PET/CT and classified each lesion as having no radiotracer uptake, equivocal uptake, or definitive uptake.

Resuts

In total, 73 metastatic sites and 3 primary tumors compatible with sites of non-clear cell RCC were identified on conventional imaging. Metastatic sites of disease included lymph nodes (n = 40), venous thrombi (n = 3), pulmonary nodules (n = 10), bone lesions (n = 15), brain lesions (n = 3), and retroperitoneal masses (n = 2). Only 10 of the 73 lesions (13.7 %) were classified as having definitive radiotracer uptake (median SUV_max = 3.25, range = 1.2-9.5), 14 lesions (19.2 %) had equivocal uptake (median SUV_max = 2.85, range = 0.5-6.5), and 49 lesions (67.1 %) had no definitive uptake above background (median SUV_max = 1.7, range = 0.2-3.0). The three primary renal tumors demonstrated lower radiotracer avidity relative to surrounding normal renal parenchyma.

Conclusions

A small proportion of sites of non-clear cell RCC showed uptake of the PSMA-targeted radiotracer [¹⁸F]DCFPyL. Unlike for clear cell RCC, the results of this study indicate that PSMA-based PET is not appropriate for imaging other RCC subtypes.

SUBMITTER: Yin Y

PROVIDER: S-EPMC9774683 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma with PSMA-Targeted [<sup>18</sup>F]DCFPyL PET/CT.

Yin Yafu Y Campbell Scott P SP Markowski Mark C MC Pierorazio Philip M PM Pomper Martin G MG Allaf Mohamad E ME Rowe Steven P SP Gorin Michael A MA

Molecular imaging and biology 20190601 3

<h4>Purpose</h4>To investigate the utility of prostate-specific membrane antigen (PSMA)-targeted [<sup>18</sup>F]DCFPyL positron emission tomography (PET)/X-ray computed tomography (CT) imaging for the detection of sites of disease in patients with metastatic non-clear cell renal cell carcinoma (RCC).<h4>Procedures</h4>Eight patients with metastatic non-clear cell RCC underwent imaging with PSMA-targeted [<sup>18</sup>F]DCFPyL PET/CT. Imaged RCC histologic subtypes included papillary RCC (n = 3) ...[more]

PMID: 30218388

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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.

Project description:BackgroundProstate Specific Membrane Antigen (PSMA) - positron emission tomography (PET) guides metastasis-directed radiotherapy (MDRT) in prostate cancer (PrCa). However, its value as a treatment response assessment tool after MDRT remains unclear. Importantly, there is limited understanding of the potential of radiotherapy (RT) to alter PSMA gene (folate hydrolase 1; FOLH1) expression.MethodologyWe reviewed a series of 11 men with oligo-metastatic PrCa (25 metastasis sites) treated with MDRT before re-staging with 18F-DCFPyL (PSMA) PET upon secondary recurrence. Acute effects of RT on PSMA protein and mRNA levels were examined with qPCR and immunoblotting in human wild-type androgen-sensitive (LNCap), castrate-resistant (22RV1) and castrate-resistant neuroendocrine (PC3 and DU145) PrCa cell lines. Xenograft tumors were analyzed with immunohistochemistry. Further, we examined PSMA expression in untreated and irradiated radio-resistant (RR) 22RV1 (22RV1-RR) and DU145 (DU145-RR) cells and xenografts selected for survival after high-dose RT.ResultsThe majority of MDRT-treated lesions showed lack of PSMA-PET/CT avidity, suggesting treatment response even after low biological effective dose (BED) MDRT. We observed similar high degree of heterogeneity of PSMA expression in both human specimens and in xenograft tumors. PSMA was highly expressed in LNCap and 22RV1 cells and tumors but not in the neuroendocrine PC3 and DU145 models. Single fraction RT caused detectable reduction in PSMA protein but not in mRNA levels in LNCap cells and did not significantly alter PSMA protein or mRNA levels in tissue culture or xenografts of the other cell lines. However, radio-resistant 22RV1-RR cells and tumors demonstrated marked decrease of PSMA transcript and protein expression over their parental counterparts.ConclusionsPSMA-PET may be a promising tool to assess RT response in oligo-metastatic PrCa. However, future systematic investigation of this concept should recognize the high degree of heterogeneity of PSMA expression within prostate tumors and the risk for loss of PSMA expression in tumor surviving curative courses of RT.

Project description:Quantitative evaluation of radiolabeled prostate-specific membrane antigen (PSMA) PET scans may be used to monitor treatment response in patients with prostate cancer (PCa). To interpret longitudinal differences in PSMA uptake, the intrinsic variability of tracer uptake in PCa lesions needs to be defined. The aim of this study was to investigate the repeatability of quantitative PET/CT measurements using 18F-DCFPyL ([2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid], a second-generation 18F-PSMA-ligand) in patients with PCa. Methods: Twelve patients with metastatic PCa were prospectively included, of whom 2 were excluded from final analyses. Patients received 2 whole-body 18F-DCFPyL PET/CT scans (median dose, 317 MBq; uptake time, 120 min) within a median of 4 d (range, 1-11 d). After semiautomatic (isocontour-based) tumor delineation, the following lesion-based metrics were derived: mean, peak, and maximum tumor-to-blood ratio; SUVmean, SUVpeak, and SUVmax normalized to body weight; tumor volume; and total lesion uptake (TLU). Additionally, patient-based total tumor volume (TTV) (sum of PSMA-positive tumor volumes) and total tumor burden (TTB) (sum of all lesion TLUs) were derived. Repeatability was analyzed using repeatability coefficients (RC) and intraclass correlation coefficients. Additionally, the effect of point-spread function (PSF) image reconstruction on the repeatability of uptake metrics was evaluated. Results: In total, 36 18F-DCFPyL PET-positive lesions were analyzed (≤5 lesions per patient). The RCs for mean, peak, and maximum tumor-to-blood ratio were 31.8%, 31.7%, and 37.3%, respectively. For SUVmean, SUVpeak, and SUVmax, the RCs were 24.4%, 25.3%, and 31.0%, respectively. All intraclass correlation coefficients were at least 0.97. Tumor volume delineations were quite repeatable, with an RC of 28.1% for individual lesion volumes and 17.0% for TTV. TTB had an RC of 23.2% and 33.4% when based on SUVmean and mean tumor-to-blood ratio, respectively. Small lesions (<4.2 cm3) had worse repeatability for volume measurements. The repeatability of SUVpeak, TLU, and all patient-level metrics was not affected by PSF reconstruction. Conclusion: 18F-DCFPyL uptake measurements are quite repeatable and can be used for clinical validation in future treatment response assessment studies. Patient-based TTV may be preferred for multicenter studies because its repeatability was both high and robust to different image reconstructions.

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Dataset Information

Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma with PSMA-Targeted [¹⁸F]DCFPyL PET/CT.

Purpose

Procedures

Resuts

Conclusions

Publications

Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma with PSMA-Targeted [<sup>18</sup>F]DCFPyL PET/CT.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma with PSMA-Targeted [18F]DCFPyL PET/CT.

Purpose

Procedures

Resuts

Conclusions

Publications

Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma with PSMA-Targeted [<sup>18</sup>F]DCFPyL PET/CT.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Inconsistent Detection of Sites of Metastatic Non-Clear Cell Renal Cell Carcinoma with PSMA-Targeted [¹⁸F]DCFPyL PET/CT.