Dataset Information

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [¹⁸F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.

ABSTRACT:

Purpose

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has impacted the management of patients with prostate cancer (PCa) in many parts of the world. PSMA-targeted endoradiotherapies are also being increasingly utilized and for these applications, the radiopharmaceutical distribution in normal organs is particularly important because it may limit the dose that can be delivered to tumors. In this study, we measured both interpatient and intrapatient variability of [¹⁸F]DCFPyL uptake in the most relevant normal organs.

Procedures

Baseline and 6-month follow-up PSMA-targeted [¹⁸F]DCFPyL PET/computed tomography (CT) scans from 39 patients with PCa were reviewed. Volumes of interest were manually drawn using the best visual approximation of the organ edge for both lacrimal glands, all four major salivary glands, the liver, the spleen, and both kidneys for all patients. The average SUV_mean, the COVs, and intraclass correlation coefficients (ICCs) across scans were calculated. Bland-Altman analyses were performed for all organs to derive repeatability coefficients (RCs).

Results

The liver demonstrated the lowest interpatient variability (13.0 and 16.6 % at baseline and follow-up, respectively), while the spleen demonstrated the largest interpatient variability (44.6 and 51.0 % at baseline and follow-up, respectively). The lowest intrapatient variability was found in the spleen (ICC 0.86) while the highest intrapatient variability was in the kidneys (ICCs 0.40-0.50). Bland-Altman analyses showed 95 % repeatability coefficients for mean uptake >?40 % for multiple organs and were highest for the lacrimal glands, kidneys, and spleen.

Conclusions

Normal organs demonstrate significant variability in uptake of the PSMA-targeted radiotracer [¹⁸F]DCFPyL. Depending on the organ, different contributions of interpatient and intrapatient factors affect the intrinsic variability. The RCs also vary significantly among the different organs were highest for the lacrimal glands, kidneys, and spleen. These findings may have important implications for the design of clinical protocols and personalized dosimetry for PSMA-targeted endoradiotherapies.

SUBMITTER: Sahakyan K

PROVIDER: S-EPMC7955793 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [<sup>18</sup>F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.

Sahakyan Karine K Li Xin X Lodge Martin A MA Werner Rudolf A RA Bundschuh Ralph A RA Bundschuh Lena L Kulkarni Harshad R HR Schuchardt Christiane C Baum Richard P RP Pienta Kenneth J KJ Pomper Martin G MG Ross Ashley E AE Gorin Michael A MA Rowe Steven P SP

Molecular imaging and biology 20200201 1

<h4>Purpose</h4>Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has impacted the management of patients with prostate cancer (PCa) in many parts of the world. PSMA-targeted endoradiotherapies are also being increasingly utilized and for these applications, the radiopharmaceutical distribution in normal organs is particularly important because it may limit the dose that can be delivered to tumors. In this study, we measured both interpatient and intra ...[more]

PMID: 31115751

Similar Datasets

Project description:18F-DCFPyL is a small-molecule inhibitor of the prostate-specific membrane antigen that has shown promise for evaluation of primary and metastatic prostate cancer using PET. Measuring the variability in normal-organ uptake of 18F-DCFPyL is necessary to understand its biodistribution, aid image interpretation, judge the reliability of scan quantification, and provide a basis for therapeutic monitoring. Methods: Sixty-five consecutive 18F-DCFPyL PET/CT scans from 64 patients with a history of prostate cancer were analyzed. Volumes of interest were defined for the lacrimal glands, major salivary glands, liver, spleen, and both kidneys. The mean SUV normalized to body mass or to lean body mass (SUL) was calculated for each volume of interest. The average SUV across all scans, the SD, and the coefficient of variation (COV) for each organ were calculated. The same parameters were also derived for a 3-cm sphere drawn in the center of the right lobe of the liver. Results: The average SUVmean for all selected organs measured was 6.6 ± 1.8 for the right lacrimal gland, 6.4 ± 1.8 for the left lacrimal gland, 9.1 ± 2.0 for the right parotid gland, 9.0 ± 2.1 for the left parotid gland, 9.6 ± 2.3 for the right submandibular gland, 9.4 ± 2.2 for the left submandibular gland, 5.0 ± 0.7 for the whole liver, 5.1 ± 0.7 for a 3-cm sphere in the liver, 4.0 ± 1.5 for the spleen, 20.1 ± 4.6 for the right kidney, and 19.4 ± 4.5 for the left kidney. SULmean was lower overall, although demonstrating similar trends. The COV of SUVmean and SULmean was lower in the liver (13.8% and 14.5%, respectively) than in any other organ and was less than the comparable COV for 18F-FDG PET. The COV of SUVmean and SULmean in the 3-cm sphere in the liver was also low and similar to the variability in the whole liver (14.2% and 14.7%, respectively). Conclusion:18F-DCFPyL uptake in normal liver demonstrates less variability than in other 18F-DCFPyL-avid organs, and its variability is less than the reported variability of 18F-FDG in liver. Variability was slightly less for SUVmean than for SULmean, suggesting that SUVmean may be the preferable parameter for quantification of images obtained with 18F-DCFPyL.

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: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: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.

Dataset Information

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [¹⁸F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.

Purpose

Procedures

Results

Conclusions

Publications

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [<sup>18</sup>F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.

Purpose

Procedures

Results

Conclusions

Publications

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [<sup>18</sup>F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [¹⁸F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.