A Phase I/II Study for Analytic Validation of 89Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer

Neeta Pandit-Taskar; Joseph A. O'Donoghue; Jeremy C. Durack; Serge K. Lyashchenko; Sarah M. Cheal; Volkan Beylergil; Robert A. Lefkowitz; Jorge A. Carrasquillo; Danny F. Martinez; Alex Mak Fung; Stephen B. Solomon; Mithat Gönen; Glenn Heller; Massimo Loda; David M. Nanus; Scott T. Tagawa; Jarett L. Feldman; Joseph R. Osborne; Jason S. Lewis; Victor E. Reuter; Wolfgang A. Weber; Neil H. Bander; Howard I. Scher; Steven M. Larson; Michael J. Morris

doi:10.1158/1078-0432.CCR-15-0552

A Phase I/II Study for Analytic Validation of ⁸⁹Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer

Neeta Pandit-Taskar, Joseph A. O'Donoghue, Jeremy C. Durack, Serge K. Lyashchenko, Sarah M. Cheal, Volkan Beylergil, Robert A. Lefkowitz, Jorge A. Carrasquillo, Danny F. Martinez, Alex Mak Fung, Stephen B. Solomon, Mithat Gönen, Glenn Heller, Massimo Loda, David M. Nanus, Scott T. Tagawa, Jarett L. Feldman, Joseph R. Osborne, Jason S. Lewis, Victor E. ReuterWolfgang A. Weber, Neil H. Bander, Howard I. Scher, Steven M. Larson, Michael J. Morris

Research output: Contribution to journal › Article › peer-review

166 Scopus citations

Abstract

Purpose: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of ⁸⁹Zr- DFO-huJ591 (⁸⁹Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology. Experimental Design: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of ⁸⁹Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites. Results: Median standardized uptake value for ⁸⁹Zr-J591-positive bone lesions (n 491) was 8.9 and for soft-tissue lesions (n 90), it was 4.8 (P < 0.00003). ⁸⁹Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, ⁸⁹Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 ⁸⁹Zr-J591-positive osseous sites and 14 of 16 ⁸⁹Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of ⁸⁹Zr-J591 was 95.2%(20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions. Conclusions: ⁸⁹Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although ⁸⁹Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer.

Original language	English
Pages (from-to)	5277-5285
Number of pages	9
Journal	Clinical Cancer Research
Volume	21
Issue number	23
DOIs	https://doi.org/10.1158/1078-0432.CCR-15-0552
State	Published - 1 Dec 2015
Externally published	Yes

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10.1158/1078-0432.CCR-15-0552

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Pandit-Taskar, N., O'Donoghue, J. A., Durack, J. C., Lyashchenko, S. K., Cheal, S. M., Beylergil, V., Lefkowitz, R. A., Carrasquillo, J. A., Martinez, D. F., Fung, A. M., Solomon, S. B., Gönen, M., Heller, G., Loda, M., Nanus, D. M., Tagawa, S. T., Feldman, J. L., Osborne, J. R., Lewis, J. S., ... Morris, M. J. (2015). A Phase I/II Study for Analytic Validation of ⁸⁹Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer. Clinical Cancer Research, 21(23), 5277-5285. https://doi.org/10.1158/1078-0432.CCR-15-0552

@article{8ddedc89a1074378ad61668001955d13,

title = "A Phase I/II Study for Analytic Validation of 89Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer",

abstract = "Purpose: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of 89Zr- DFO-huJ591 (89Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology. Experimental Design: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of 89Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites. Results: Median standardized uptake value for 89Zr-J591-positive bone lesions (n 491) was 8.9 and for soft-tissue lesions (n 90), it was 4.8 (P < 0.00003). 89Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, 89Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 89Zr-J591-positive osseous sites and 14 of 16 89Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of 89Zr-J591 was 95.2%(20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions. Conclusions: 89Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although 89Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer.",

author = "Neeta Pandit-Taskar and O'Donoghue, {Joseph A.} and Durack, {Jeremy C.} and Lyashchenko, {Serge K.} and Cheal, {Sarah M.} and Volkan Beylergil and Lefkowitz, {Robert A.} and Carrasquillo, {Jorge A.} and Martinez, {Danny F.} and Fung, {Alex Mak} and Solomon, {Stephen B.} and Mithat G{\"o}nen and Glenn Heller and Massimo Loda and Nanus, {David M.} and Tagawa, {Scott T.} and Feldman, {Jarett L.} and Osborne, {Joseph R.} and Lewis, {Jason S.} and Reuter, {Victor E.} and Weber, {Wolfgang A.} and Bander, {Neil H.} and Scher, {Howard I.} and Larson, {Steven M.} and Morris, {Michael J.}",

note = "Publisher Copyright: {\textcopyright} 2015 American Association for Cancer Research.",

year = "2015",

month = dec,

day = "1",

doi = "10.1158/1078-0432.CCR-15-0552",

language = "English",

volume = "21",

pages = "5277--5285",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "23",

}

Pandit-Taskar, N, O'Donoghue, JA, Durack, JC, Lyashchenko, SK, Cheal, SM, Beylergil, V, Lefkowitz, RA, Carrasquillo, JA, Martinez, DF, Fung, AM, Solomon, SB, Gönen, M, Heller, G, Loda, M, Nanus, DM, Tagawa, ST, Feldman, JL, Osborne, JR, Lewis, JS, Reuter, VE, Weber, WA, Bander, NH, Scher, HI, Larson, SM & Morris, MJ 2015, 'A Phase I/II Study for Analytic Validation of ⁸⁹Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer', Clinical Cancer Research, vol. 21, no. 23, pp. 5277-5285. https://doi.org/10.1158/1078-0432.CCR-15-0552

TY - JOUR

T1 - A Phase I/II Study for Analytic Validation of 89Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer

AU - Pandit-Taskar, Neeta

AU - O'Donoghue, Joseph A.

AU - Durack, Jeremy C.

AU - Lyashchenko, Serge K.

AU - Cheal, Sarah M.

AU - Beylergil, Volkan

AU - Lefkowitz, Robert A.

AU - Carrasquillo, Jorge A.

AU - Martinez, Danny F.

AU - Fung, Alex Mak

AU - Solomon, Stephen B.

AU - Gönen, Mithat

AU - Heller, Glenn

AU - Loda, Massimo

AU - Nanus, David M.

AU - Tagawa, Scott T.

AU - Feldman, Jarett L.

AU - Osborne, Joseph R.

AU - Lewis, Jason S.

AU - Reuter, Victor E.

AU - Weber, Wolfgang A.

AU - Bander, Neil H.

AU - Scher, Howard I.

AU - Larson, Steven M.

AU - Morris, Michael J.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Purpose: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of 89Zr- DFO-huJ591 (89Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology. Experimental Design: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of 89Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites. Results: Median standardized uptake value for 89Zr-J591-positive bone lesions (n 491) was 8.9 and for soft-tissue lesions (n 90), it was 4.8 (P < 0.00003). 89Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, 89Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 89Zr-J591-positive osseous sites and 14 of 16 89Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of 89Zr-J591 was 95.2%(20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions. Conclusions: 89Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although 89Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer.

AB - Purpose: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of 89Zr- DFO-huJ591 (89Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology. Experimental Design: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of 89Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites. Results: Median standardized uptake value for 89Zr-J591-positive bone lesions (n 491) was 8.9 and for soft-tissue lesions (n 90), it was 4.8 (P < 0.00003). 89Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, 89Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 89Zr-J591-positive osseous sites and 14 of 16 89Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of 89Zr-J591 was 95.2%(20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions. Conclusions: 89Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although 89Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=84945484394&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-15-0552

DO - 10.1158/1078-0432.CCR-15-0552

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C2 - 26175541

AN - SCOPUS:84945484394

SN - 1078-0432

VL - 21

SP - 5277

EP - 5285

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 23

ER -

A Phase I/II Study for Analytic Validation of ⁸⁹Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer

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