Reproducibility and repeatability of semiquantitative 18F-Fluorodihydrotestosterone uptake metrics in castration-resistant prostate cancer metastases

A prospective multicenter study

Hebert Alberto Vargas, Gem M. Kramer, Andrew M. Scott, Andrew Weickhardt, Andreas A. Meier, Nicole Parada, Bradley J. Beattie, John L. Humm, Kevin D. Staton, Pat B. Zanzonico, Serge K. Lyashchenko, Jason S. Lewis, Maqsood Yaqub, Ramon E. Sosa, Alfons J. Van Den Eertwegh, Ian D. Davis, Uwe Ackermann, Kunthi Pathmaraj, Robert C. Schuit, Albert D. Windhorst & 7 others Sue Chua, Wolfgang A. Weber, Steven M. Larson, Howard I. Scher, Adriaan A. Lammertsma, Otto S. Hoekstra, Michael J. Morris

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

18F-fluorodihydrotestosterone (18F-FDHT) is a radiolabeled analog of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. Methods: We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancer patients undergoing 2 (test/retest) 18F-FDHT PET/CT scans on 2 consecutive days. Two independent readers evaluated all examinations and recorded SUVs, androgen receptor-positive tumor volumes, and total lesion uptake for the most avid lesion detected in each of 32 predefined anatomic regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and retest scans. Linear regression analyses, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to evaluate repeatability of 18F-FDHT metrics. The coefficient of variation and ICC were used to assess interobserver reproducibility. Results: Twenty-seven patients with 140 18FFDHT- avid regions were included. The best repeatability among 18F-FDHT uptake metrics was found for SUV metrics (SUVmax, SUVmean, and SUVpeak), with no significant differences in repeatability among them. Correlations between the test and retest scans were strong for all SUV metrics (R2 ≥ 0.92; ICC $ 0.97). The RCs of the SUV metrics ranged from 21.3% (SUVpeak) to 24.6%(SUVmax). The test and retest androgen receptor-positive tumor volumes and TLU, respectively, were highly correlated (R2 and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs > 46.4%). The prostate-specific antigen levels, Gleason score, weight, and age did not affect repeatability, nor did total injected activity, uptake measurement time, or differences in uptake time between the 2 scans. Including the most avid lesion per patient, the 5 most avid lesions per patient, only lesions 4.2 mL or more, only lesions with an SUV of 4 g/mL or more, or normalizing of SUV to area under the parent plasma activity concentration-time curve did not significantly affect repeatability. All metrics showed high interobserver reproducibility (ICC > 0.98; coefficient of variation < 0.2%-10.8%). Conclusion: Uptake metrics derived from 18F-FDHT PET/CT show high repeatability and interobserver reproducibility.

Original languageEnglish
Pages (from-to)1516-1523
Number of pages8
JournalJournal of Nuclear Medicine
Volume59
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • FDHT
  • PET
  • Prostate cancer
  • Repeatability
  • Reproducibility

Cite this

Vargas, Hebert Alberto ; Kramer, Gem M. ; Scott, Andrew M. ; Weickhardt, Andrew ; Meier, Andreas A. ; Parada, Nicole ; Beattie, Bradley J. ; Humm, John L. ; Staton, Kevin D. ; Zanzonico, Pat B. ; Lyashchenko, Serge K. ; Lewis, Jason S. ; Yaqub, Maqsood ; Sosa, Ramon E. ; Van Den Eertwegh, Alfons J. ; Davis, Ian D. ; Ackermann, Uwe ; Pathmaraj, Kunthi ; Schuit, Robert C. ; Windhorst, Albert D. ; Chua, Sue ; Weber, Wolfgang A. ; Larson, Steven M. ; Scher, Howard I. ; Lammertsma, Adriaan A. ; Hoekstra, Otto S. ; Morris, Michael J. / Reproducibility and repeatability of semiquantitative 18F-Fluorodihydrotestosterone uptake metrics in castration-resistant prostate cancer metastases : A prospective multicenter study. In: Journal of Nuclear Medicine. 2018 ; Vol. 59, No. 10. pp. 1516-1523.
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title = "Reproducibility and repeatability of semiquantitative 18F-Fluorodihydrotestosterone uptake metrics in castration-resistant prostate cancer metastases: A prospective multicenter study",
abstract = "18F-fluorodihydrotestosterone (18F-FDHT) is a radiolabeled analog of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. Methods: We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancer patients undergoing 2 (test/retest) 18F-FDHT PET/CT scans on 2 consecutive days. Two independent readers evaluated all examinations and recorded SUVs, androgen receptor-positive tumor volumes, and total lesion uptake for the most avid lesion detected in each of 32 predefined anatomic regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and retest scans. Linear regression analyses, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to evaluate repeatability of 18F-FDHT metrics. The coefficient of variation and ICC were used to assess interobserver reproducibility. Results: Twenty-seven patients with 140 18FFDHT- avid regions were included. The best repeatability among 18F-FDHT uptake metrics was found for SUV metrics (SUVmax, SUVmean, and SUVpeak), with no significant differences in repeatability among them. Correlations between the test and retest scans were strong for all SUV metrics (R2 ≥ 0.92; ICC $ 0.97). The RCs of the SUV metrics ranged from 21.3{\%} (SUVpeak) to 24.6{\%}(SUVmax). The test and retest androgen receptor-positive tumor volumes and TLU, respectively, were highly correlated (R2 and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs > 46.4{\%}). The prostate-specific antigen levels, Gleason score, weight, and age did not affect repeatability, nor did total injected activity, uptake measurement time, or differences in uptake time between the 2 scans. Including the most avid lesion per patient, the 5 most avid lesions per patient, only lesions 4.2 mL or more, only lesions with an SUV of 4 g/mL or more, or normalizing of SUV to area under the parent plasma activity concentration-time curve did not significantly affect repeatability. All metrics showed high interobserver reproducibility (ICC > 0.98; coefficient of variation < 0.2{\%}-10.8{\%}). Conclusion: Uptake metrics derived from 18F-FDHT PET/CT show high repeatability and interobserver reproducibility.",
keywords = "FDHT, PET, Prostate cancer, Repeatability, Reproducibility",
author = "Vargas, {Hebert Alberto} and Kramer, {Gem M.} and Scott, {Andrew M.} and Andrew Weickhardt and Meier, {Andreas A.} and Nicole Parada and Beattie, {Bradley J.} and Humm, {John L.} and Staton, {Kevin D.} and Zanzonico, {Pat B.} and Lyashchenko, {Serge K.} and Lewis, {Jason S.} and Maqsood Yaqub and Sosa, {Ramon E.} and {Van Den Eertwegh}, {Alfons J.} and Davis, {Ian D.} and Uwe Ackermann and Kunthi Pathmaraj and Schuit, {Robert C.} and Windhorst, {Albert D.} and Sue Chua and Weber, {Wolfgang A.} and Larson, {Steven M.} and Scher, {Howard I.} and Lammertsma, {Adriaan A.} and Hoekstra, {Otto S.} and Morris, {Michael J.}",
year = "2018",
month = "10",
day = "1",
doi = "10.2967/jnumed.117.206490",
language = "English",
volume = "59",
pages = "1516--1523",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
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}

Vargas, HA, Kramer, GM, Scott, AM, Weickhardt, A, Meier, AA, Parada, N, Beattie, BJ, Humm, JL, Staton, KD, Zanzonico, PB, Lyashchenko, SK, Lewis, JS, Yaqub, M, Sosa, RE, Van Den Eertwegh, AJ, Davis, ID, Ackermann, U, Pathmaraj, K, Schuit, RC, Windhorst, AD, Chua, S, Weber, WA, Larson, SM, Scher, HI, Lammertsma, AA, Hoekstra, OS & Morris, MJ 2018, 'Reproducibility and repeatability of semiquantitative 18F-Fluorodihydrotestosterone uptake metrics in castration-resistant prostate cancer metastases: A prospective multicenter study', Journal of Nuclear Medicine, vol. 59, no. 10, pp. 1516-1523. https://doi.org/10.2967/jnumed.117.206490

Reproducibility and repeatability of semiquantitative 18F-Fluorodihydrotestosterone uptake metrics in castration-resistant prostate cancer metastases : A prospective multicenter study. / Vargas, Hebert Alberto; Kramer, Gem M.; Scott, Andrew M.; Weickhardt, Andrew; Meier, Andreas A.; Parada, Nicole; Beattie, Bradley J.; Humm, John L.; Staton, Kevin D.; Zanzonico, Pat B.; Lyashchenko, Serge K.; Lewis, Jason S.; Yaqub, Maqsood; Sosa, Ramon E.; Van Den Eertwegh, Alfons J.; Davis, Ian D.; Ackermann, Uwe; Pathmaraj, Kunthi; Schuit, Robert C.; Windhorst, Albert D.; Chua, Sue; Weber, Wolfgang A.; Larson, Steven M.; Scher, Howard I.; Lammertsma, Adriaan A.; Hoekstra, Otto S.; Morris, Michael J.

In: Journal of Nuclear Medicine, Vol. 59, No. 10, 01.10.2018, p. 1516-1523.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Reproducibility and repeatability of semiquantitative 18F-Fluorodihydrotestosterone uptake metrics in castration-resistant prostate cancer metastases

T2 - A prospective multicenter study

AU - Vargas, Hebert Alberto

AU - Kramer, Gem M.

AU - Scott, Andrew M.

AU - Weickhardt, Andrew

AU - Meier, Andreas A.

AU - Parada, Nicole

AU - Beattie, Bradley J.

AU - Humm, John L.

AU - Staton, Kevin D.

AU - Zanzonico, Pat B.

AU - Lyashchenko, Serge K.

AU - Lewis, Jason S.

AU - Yaqub, Maqsood

AU - Sosa, Ramon E.

AU - Van Den Eertwegh, Alfons J.

AU - Davis, Ian D.

AU - Ackermann, Uwe

AU - Pathmaraj, Kunthi

AU - Schuit, Robert C.

AU - Windhorst, Albert D.

AU - Chua, Sue

AU - Weber, Wolfgang A.

AU - Larson, Steven M.

AU - Scher, Howard I.

AU - Lammertsma, Adriaan A.

AU - Hoekstra, Otto S.

AU - Morris, Michael J.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 18F-fluorodihydrotestosterone (18F-FDHT) is a radiolabeled analog of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. Methods: We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancer patients undergoing 2 (test/retest) 18F-FDHT PET/CT scans on 2 consecutive days. Two independent readers evaluated all examinations and recorded SUVs, androgen receptor-positive tumor volumes, and total lesion uptake for the most avid lesion detected in each of 32 predefined anatomic regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and retest scans. Linear regression analyses, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to evaluate repeatability of 18F-FDHT metrics. The coefficient of variation and ICC were used to assess interobserver reproducibility. Results: Twenty-seven patients with 140 18FFDHT- avid regions were included. The best repeatability among 18F-FDHT uptake metrics was found for SUV metrics (SUVmax, SUVmean, and SUVpeak), with no significant differences in repeatability among them. Correlations between the test and retest scans were strong for all SUV metrics (R2 ≥ 0.92; ICC $ 0.97). The RCs of the SUV metrics ranged from 21.3% (SUVpeak) to 24.6%(SUVmax). The test and retest androgen receptor-positive tumor volumes and TLU, respectively, were highly correlated (R2 and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs > 46.4%). The prostate-specific antigen levels, Gleason score, weight, and age did not affect repeatability, nor did total injected activity, uptake measurement time, or differences in uptake time between the 2 scans. Including the most avid lesion per patient, the 5 most avid lesions per patient, only lesions 4.2 mL or more, only lesions with an SUV of 4 g/mL or more, or normalizing of SUV to area under the parent plasma activity concentration-time curve did not significantly affect repeatability. All metrics showed high interobserver reproducibility (ICC > 0.98; coefficient of variation < 0.2%-10.8%). Conclusion: Uptake metrics derived from 18F-FDHT PET/CT show high repeatability and interobserver reproducibility.

AB - 18F-fluorodihydrotestosterone (18F-FDHT) is a radiolabeled analog of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. Methods: We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancer patients undergoing 2 (test/retest) 18F-FDHT PET/CT scans on 2 consecutive days. Two independent readers evaluated all examinations and recorded SUVs, androgen receptor-positive tumor volumes, and total lesion uptake for the most avid lesion detected in each of 32 predefined anatomic regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and retest scans. Linear regression analyses, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to evaluate repeatability of 18F-FDHT metrics. The coefficient of variation and ICC were used to assess interobserver reproducibility. Results: Twenty-seven patients with 140 18FFDHT- avid regions were included. The best repeatability among 18F-FDHT uptake metrics was found for SUV metrics (SUVmax, SUVmean, and SUVpeak), with no significant differences in repeatability among them. Correlations between the test and retest scans were strong for all SUV metrics (R2 ≥ 0.92; ICC $ 0.97). The RCs of the SUV metrics ranged from 21.3% (SUVpeak) to 24.6%(SUVmax). The test and retest androgen receptor-positive tumor volumes and TLU, respectively, were highly correlated (R2 and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs > 46.4%). The prostate-specific antigen levels, Gleason score, weight, and age did not affect repeatability, nor did total injected activity, uptake measurement time, or differences in uptake time between the 2 scans. Including the most avid lesion per patient, the 5 most avid lesions per patient, only lesions 4.2 mL or more, only lesions with an SUV of 4 g/mL or more, or normalizing of SUV to area under the parent plasma activity concentration-time curve did not significantly affect repeatability. All metrics showed high interobserver reproducibility (ICC > 0.98; coefficient of variation < 0.2%-10.8%). Conclusion: Uptake metrics derived from 18F-FDHT PET/CT show high repeatability and interobserver reproducibility.

KW - FDHT

KW - PET

KW - Prostate cancer

KW - Repeatability

KW - Reproducibility

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U2 - 10.2967/jnumed.117.206490

DO - 10.2967/jnumed.117.206490

M3 - Article

VL - 59

SP - 1516

EP - 1523

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 10

ER -