Consecutive Prostate-Specific Membrane Antigen (PSMA) and Antigen Receptor (AR) PET Imaging Shows Positive Correlation with AR and PSMA Protein Expression in Primary Hormone-Naïve Prostate Cancer (2024)

Abstract

The present study was carried out to investigate whether PET imaging can be used as a potential substitute for immunohistochemical analysis of tumor samples in prostate cancer (PC) patients. Correlation between imaging signals of 2 PET tracers and the corresponding target structures was assessed. The first tracer was [68Ga]Ga-PSMA (prostate-specific membrane antigen)-HBED-CC (N,N9-bis [2-hydroxy- 5-(carboxyethyl)benzyl]ethylenediamine-N,N9-diacetic acid) [68Ga]Ga- PSMAHBED-CC ([68Ga]PSMA), which is already implemented in clinical routines. The second tracer was 16b-[18F]fluoro-5a-dihydrotestosterone (16b-[18F]FDHT), which binds to the androgen receptor (AR). The AR is particularly interesting in PC, because AR expression status and its shift during therapy might directly influence patient care. Methods: This prospective, explorative clinical study included 10 newly diagnosed PC patients. Each patient underwent [68Ga]PSMA PET/MRI and [18F]FDHT PET/MRI scans before prostatectomy. Cancer SUVs were determined and related to background SUVs. After prostatectomy, tumor tissue was sampled, and AR and prostate-specific membrane antigen (PSMA) expression was determined. AR and PSMA expression was evaluated quantitatively with the open-source bioimage analysis software QuPath and with a 4-tier rating system. Correlation between imaging signals and marker expression was statistically assessed. Results: For [18F]FDHT, the SUVmax/SUVbackground ratio showed a significant, strong correlation (r = 0.72; P = 0.019) with the AR optical density of the correlating tissue sample. The correlation between PSMA optical density and the [68Ga]PSMA SUVmax/SUVbackground ratio was not significant (P = 0.061), yet a positive correlation trend could be observed (r = 0.61). SUVmax/ SUVbackground ratios were higher for [68Ga]PSMA (mean 6 SD, 34.9 6 24.8) than for [18F]FDHT (4.86 1.2). In line with these findings, the tumor detection rates were 90% for the [68Ga]PSMA PET scan but only 40% for the [18F]FDHT PET scan. The 4-tier rating of PSMA staining intensity yielded very hom*ogeneous results, with values of 31 for most subjects (90%). AR staining was rated as 11 in 2 patients (20%), 21 in 4 patients (40%), and 31 in 4 patients (40%). Conclusion: [18F]FDHT PET may be useful for monitoring AR expression and alterations in AR expression during treatment of PC patients. This approach may facilitate early detection of treatment resistance and allows for adaptation of therapy to prevent cancer progression. [18F]FDHT PET is inferior to [68Ga]PSMA PET for primary PC diagnosis, but the correlation between [68Ga]PSMA SUVs and PSMA expression is weaker than that between [18F]FDHT and the AR.

OriginalspracheEnglisch
Seiten (von - bis)863-868
Seitenumfang6
FachzeitschriftJournal of Nuclear Medicine
Jahrgang64
Ausgabenummer6
DOIs
PublikationsstatusVeröffentlicht - 2023

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al Jalali, V., Wasinger, G., Rasul, S., Grubmüller, B., Wulkersdorfer, B., Balber, T., Mitterhauser, M., Simon, J., Hacker, M., Shariat, S., Egger, G., & Zeitlinger, M. (2023). Consecutive Prostate-Specific Membrane Antigen (PSMA) and Antigen Receptor (AR) PET Imaging Shows Positive Correlation with AR and PSMA Protein Expression in Primary Hormone-Naïve Prostate Cancer. Journal of Nuclear Medicine, 64(6), 863-868. https://doi.org/10.2967/jnumed.122.264981

al Jalali, Valentin ; Wasinger, Gabriel ; Rasul, Sazan et al. / Consecutive Prostate-Specific Membrane Antigen (PSMA) and Antigen Receptor (AR) PET Imaging Shows Positive Correlation with AR and PSMA Protein Expression in Primary Hormone-Naïve Prostate Cancer. in: Journal of Nuclear Medicine. 2023 ; Band 64, Nr. 6. S. 863-868.

@article{787180c21c634b25aca76c486cae0ade,

title = "Consecutive Prostate-Specific Membrane Antigen (PSMA) and Antigen Receptor (AR) PET Imaging Shows Positive Correlation with AR and PSMA Protein Expression in Primary Hormone-Na{\"i}ve Prostate Cancer",

abstract = "The present study was carried out to investigate whether PET imaging can be used as a potential substitute for immunohistochemical analysis of tumor samples in prostate cancer (PC) patients. Correlation between imaging signals of 2 PET tracers and the corresponding target structures was assessed. The first tracer was [68Ga]Ga-PSMA (prostate-specific membrane antigen)-HBED-CC (N,N9-bis [2-hydroxy- 5-(carboxyethyl)benzyl]ethylenediamine-N,N9-diacetic acid) [68Ga]Ga- PSMAHBED-CC ([68Ga]PSMA), which is already implemented in clinical routines. The second tracer was 16b-[18F]fluoro-5a-dihydrotestosterone (16b-[18F]FDHT), which binds to the androgen receptor (AR). The AR is particularly interesting in PC, because AR expression status and its shift during therapy might directly influence patient care. Methods: This prospective, explorative clinical study included 10 newly diagnosed PC patients. Each patient underwent [68Ga]PSMA PET/MRI and [18F]FDHT PET/MRI scans before prostatectomy. Cancer SUVs were determined and related to background SUVs. After prostatectomy, tumor tissue was sampled, and AR and prostate-specific membrane antigen (PSMA) expression was determined. AR and PSMA expression was evaluated quantitatively with the open-source bioimage analysis software QuPath and with a 4-tier rating system. Correlation between imaging signals and marker expression was statistically assessed. Results: For [18F]FDHT, the SUVmax/SUVbackground ratio showed a significant, strong correlation (r = 0.72; P = 0.019) with the AR optical density of the correlating tissue sample. The correlation between PSMA optical density and the [68Ga]PSMA SUVmax/SUVbackground ratio was not significant (P = 0.061), yet a positive correlation trend could be observed (r = 0.61). SUVmax/ SUVbackground ratios were higher for [68Ga]PSMA (mean 6 SD, 34.9 6 24.8) than for [18F]FDHT (4.86 1.2). In line with these findings, the tumor detection rates were 90% for the [68Ga]PSMA PET scan but only 40% for the [18F]FDHT PET scan. The 4-tier rating of PSMA staining intensity yielded very hom*ogeneous results, with values of 31 for most subjects (90%). AR staining was rated as 11 in 2 patients (20%), 21 in 4 patients (40%), and 31 in 4 patients (40%). Conclusion: [18F]FDHT PET may be useful for monitoring AR expression and alterations in AR expression during treatment of PC patients. This approach may facilitate early detection of treatment resistance and allows for adaptation of therapy to prevent cancer progression. [18F]FDHT PET is inferior to [68Ga]PSMA PET for primary PC diagnosis, but the correlation between [68Ga]PSMA SUVs and PSMA expression is weaker than that between [18F]FDHT and the AR.",

keywords = "AR protein expression, primary hormone-na{\"i}ve prostate cancer, PSMA protein expression, [F]FDHT PET, [Ga]PSMA PET",

author = "{al Jalali}, Valentin and Gabriel Wasinger and Sazan Rasul and Bernhard Grubm{\"u}ller and Beatrix Wulkersdorfer and Theresa Balber and Markus Mitterhauser and Judit Simon and Marcus Hacker and Shahrokh Shariat and Gerda Egger and Markus Zeitlinger",

note = "Accession Number: WOS:001030803100007 PubMed ID: 36657982",

year = "2023",

doi = "10.2967/jnumed.122.264981",

language = "English",

volume = "64",

pages = "863--868",

journal = "The Journal of Nuclear Medicine",

issn = "0161-5505",

publisher = "Society of Nuclear Medicine",

number = "6",

}

al Jalali, V, Wasinger, G, Rasul, S, Grubmüller, B, Wulkersdorfer, B, Balber, T, Mitterhauser, M, Simon, J, Hacker, M, Shariat, S, Egger, G & Zeitlinger, M 2023, 'Consecutive Prostate-Specific Membrane Antigen (PSMA) and Antigen Receptor (AR) PET Imaging Shows Positive Correlation with AR and PSMA Protein Expression in Primary Hormone-Naïve Prostate Cancer', Journal of Nuclear Medicine, Jg. 64, Nr. 6, S. 863-868. https://doi.org/10.2967/jnumed.122.264981

Consecutive Prostate-Specific Membrane Antigen (PSMA) and Antigen Receptor (AR) PET Imaging Shows Positive Correlation with AR and PSMA Protein Expression in Primary Hormone-Naïve Prostate Cancer. / al Jalali, Valentin; Wasinger, Gabriel; Rasul, Sazan et al.

in: Journal of Nuclear Medicine, Band 64, Nr. 6, 2023, S. 863-868.

Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed

TY - JOUR

T1 - Consecutive Prostate-Specific Membrane Antigen (PSMA) and Antigen Receptor (AR) PET Imaging Shows Positive Correlation with AR and PSMA Protein Expression in Primary Hormone-Naïve Prostate Cancer

AU - al Jalali, Valentin

AU - Wasinger, Gabriel

AU - Rasul, Sazan

AU - Grubmüller, Bernhard

AU - Wulkersdorfer, Beatrix

AU - Balber, Theresa

AU - Mitterhauser, Markus

AU - Simon, Judit

AU - Hacker, Marcus

AU - Shariat, Shahrokh

AU - Egger, Gerda

AU - Zeitlinger, Markus

N1 - Accession Number: WOS:001030803100007PubMed ID: 36657982

PY - 2023

Y1 - 2023

N2 - The present study was carried out to investigate whether PET imaging can be used as a potential substitute for immunohistochemical analysis of tumor samples in prostate cancer (PC) patients. Correlation between imaging signals of 2 PET tracers and the corresponding target structures was assessed. The first tracer was [68Ga]Ga-PSMA (prostate-specific membrane antigen)-HBED-CC (N,N9-bis [2-hydroxy- 5-(carboxyethyl)benzyl]ethylenediamine-N,N9-diacetic acid) [68Ga]Ga- PSMAHBED-CC ([68Ga]PSMA), which is already implemented in clinical routines. The second tracer was 16b-[18F]fluoro-5a-dihydrotestosterone (16b-[18F]FDHT), which binds to the androgen receptor (AR). The AR is particularly interesting in PC, because AR expression status and its shift during therapy might directly influence patient care. Methods: This prospective, explorative clinical study included 10 newly diagnosed PC patients. Each patient underwent [68Ga]PSMA PET/MRI and [18F]FDHT PET/MRI scans before prostatectomy. Cancer SUVs were determined and related to background SUVs. After prostatectomy, tumor tissue was sampled, and AR and prostate-specific membrane antigen (PSMA) expression was determined. AR and PSMA expression was evaluated quantitatively with the open-source bioimage analysis software QuPath and with a 4-tier rating system. Correlation between imaging signals and marker expression was statistically assessed. Results: For [18F]FDHT, the SUVmax/SUVbackground ratio showed a significant, strong correlation (r = 0.72; P = 0.019) with the AR optical density of the correlating tissue sample. The correlation between PSMA optical density and the [68Ga]PSMA SUVmax/SUVbackground ratio was not significant (P = 0.061), yet a positive correlation trend could be observed (r = 0.61). SUVmax/ SUVbackground ratios were higher for [68Ga]PSMA (mean 6 SD, 34.9 6 24.8) than for [18F]FDHT (4.86 1.2). In line with these findings, the tumor detection rates were 90% for the [68Ga]PSMA PET scan but only 40% for the [18F]FDHT PET scan. The 4-tier rating of PSMA staining intensity yielded very hom*ogeneous results, with values of 31 for most subjects (90%). AR staining was rated as 11 in 2 patients (20%), 21 in 4 patients (40%), and 31 in 4 patients (40%). Conclusion: [18F]FDHT PET may be useful for monitoring AR expression and alterations in AR expression during treatment of PC patients. This approach may facilitate early detection of treatment resistance and allows for adaptation of therapy to prevent cancer progression. [18F]FDHT PET is inferior to [68Ga]PSMA PET for primary PC diagnosis, but the correlation between [68Ga]PSMA SUVs and PSMA expression is weaker than that between [18F]FDHT and the AR.

AB - The present study was carried out to investigate whether PET imaging can be used as a potential substitute for immunohistochemical analysis of tumor samples in prostate cancer (PC) patients. Correlation between imaging signals of 2 PET tracers and the corresponding target structures was assessed. The first tracer was [68Ga]Ga-PSMA (prostate-specific membrane antigen)-HBED-CC (N,N9-bis [2-hydroxy- 5-(carboxyethyl)benzyl]ethylenediamine-N,N9-diacetic acid) [68Ga]Ga- PSMAHBED-CC ([68Ga]PSMA), which is already implemented in clinical routines. The second tracer was 16b-[18F]fluoro-5a-dihydrotestosterone (16b-[18F]FDHT), which binds to the androgen receptor (AR). The AR is particularly interesting in PC, because AR expression status and its shift during therapy might directly influence patient care. Methods: This prospective, explorative clinical study included 10 newly diagnosed PC patients. Each patient underwent [68Ga]PSMA PET/MRI and [18F]FDHT PET/MRI scans before prostatectomy. Cancer SUVs were determined and related to background SUVs. After prostatectomy, tumor tissue was sampled, and AR and prostate-specific membrane antigen (PSMA) expression was determined. AR and PSMA expression was evaluated quantitatively with the open-source bioimage analysis software QuPath and with a 4-tier rating system. Correlation between imaging signals and marker expression was statistically assessed. Results: For [18F]FDHT, the SUVmax/SUVbackground ratio showed a significant, strong correlation (r = 0.72; P = 0.019) with the AR optical density of the correlating tissue sample. The correlation between PSMA optical density and the [68Ga]PSMA SUVmax/SUVbackground ratio was not significant (P = 0.061), yet a positive correlation trend could be observed (r = 0.61). SUVmax/ SUVbackground ratios were higher for [68Ga]PSMA (mean 6 SD, 34.9 6 24.8) than for [18F]FDHT (4.86 1.2). In line with these findings, the tumor detection rates were 90% for the [68Ga]PSMA PET scan but only 40% for the [18F]FDHT PET scan. The 4-tier rating of PSMA staining intensity yielded very hom*ogeneous results, with values of 31 for most subjects (90%). AR staining was rated as 11 in 2 patients (20%), 21 in 4 patients (40%), and 31 in 4 patients (40%). Conclusion: [18F]FDHT PET may be useful for monitoring AR expression and alterations in AR expression during treatment of PC patients. This approach may facilitate early detection of treatment resistance and allows for adaptation of therapy to prevent cancer progression. [18F]FDHT PET is inferior to [68Ga]PSMA PET for primary PC diagnosis, but the correlation between [68Ga]PSMA SUVs and PSMA expression is weaker than that between [18F]FDHT and the AR.

KW - AR protein expression

KW - primary hormone-naïve prostate cancer

KW - PSMA protein expression

KW - [F]FDHT PET

KW - [Ga]PSMA PET

UR - http://www.scopus.com/inward/record.url?scp=85159303980&partnerID=8YFLogxK

U2 - 10.2967/jnumed.122.264981

DO - 10.2967/jnumed.122.264981

M3 - Article

C2 - 36657982

AN - SCOPUS:85159303980

VL - 64

SP - 863

EP - 868

JO - The Journal of Nuclear Medicine

JF - The Journal of Nuclear Medicine

SN - 0161-5505

IS - 6

ER -

al Jalali V, Wasinger G, Rasul S, Grubmüller B, Wulkersdorfer B, Balber T et al. Consecutive Prostate-Specific Membrane Antigen (PSMA) and Antigen Receptor (AR) PET Imaging Shows Positive Correlation with AR and PSMA Protein Expression in Primary Hormone-Naïve Prostate Cancer. Journal of Nuclear Medicine. 2023;64(6):863-868. doi: 10.2967/jnumed.122.264981

Consecutive Prostate-Specific Membrane Antigen (PSMA) and Antigen Receptor (AR) PET Imaging Shows Positive Correlation with AR and PSMA Protein Expression in Primary Hormone-Naïve Prostate Cancer (2024)

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