Breast Cancer 18F-ISO-1 Uptake as a Marker of Proliferation Status

Elizabeth S. McDonald; Robert K. Doot; Anthony J. Young; Erin K. Schubert; Julia Tchou; Daniel A. Pryma; Michael D. Farwell; Anupma Nayak; Amy Ziober; Michael D. Feldman; Angela DeMichele; Amy S. Clark; Payal D. Shah; Hsiaoju Lee; Sean D. Carlin; Robert H. Mach; David A. Mankoff

doi:10.2967/jnumed.119.232363

Breast Cancer ¹⁸F-ISO-1 Uptake as a Marker of Proliferation Status

Elizabeth S. McDonald, Robert K. Doot, Anthony J. Young, Erin K. Schubert, Julia Tchou, Daniel A. Pryma, Michael D. Farwell, Anupma Nayak, Amy Ziober, Michael D. Feldman, Angela DeMichele, Amy S. Clark, Payal D. Shah, Hsiaoju Lee, Sean D. Carlin, Robert H. Mach, David A. Mankoff

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

29 Scopus citations

Abstract

The σ₂ receptor is a potential in vivo target for measuring proliferative status in cancer. The feasibility of using N-(4-(6, 7-dimethoxy-3, 4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-¹⁸F-fluoroethoxy)-5-methylbenzamide (¹⁸F-ISO-1) to image solid tumors in lymphoma, breast cancer, and head and neck cancer has been previously established. Here, we report the results of the first dedicated clinical trial of ¹⁸F-ISO-1 in women with primary breast cancer. Our study objective was to determine whether ¹⁸F-ISO-1 PET could provide an in vivo measure of tumor proliferative status, and we hypothesized that uptake would correlate with a tissue-based assay of proliferation, namely Ki-67 expression. Methods: Twenty-eight women with 29 primary invasive breast cancers were prospectively enrolled in a clinical trial (NCT 02284919) between March 2015 and January 2017. Each received an injection of 278–527 MBq of ¹⁸F-ISO-1 and then underwent PET/CT imaging of the breasts 50–55 min later. In vivo uptake of ¹⁸F-ISO-1 was quantitated by SUV_max and distribution volume ratios and was compared with ex vivo immunohistochemistry for Ki-67. Wilcoxon rank-sum tests assessed uptake differences across Ki-67 thresholds, and Spearman correlation tested associations between uptake and Ki-67. Results: Tumor SUV_max (median, 2.0 g/mL; range, 1.3–3.3 g/mL), partial-volume–corrected SUV_max, and SUV ratios were tested against Ki-67. Tumors stratified into the high–Ki-67 ($20%) group had SUV_max greater than the low–Ki-67 (, 20%) group (P 5 0.02). SUV_max exhibited a positive correlation with Ki-67 across all breast cancer subtypes (ρ 5 0.46, P 5 0.01, n 5 29). Partial-volume–corrected SUV_max was positively correlated with Ki-67 for invasive ductal carcinoma (ρ 5 0.51, P 5 0.02, n 5 21). Tumor–to–normal-tissue ratios and tumor distribution volume ratio did not correlate with Ki-67 (P . 0.05). Conclusion: ¹⁸F-ISO-1 uptake in breast cancer modestly correlates with an in vitro assay of proliferation.

Original language	English
Pages (from-to)	665-670
Number of pages	6
Journal	Journal of Nuclear Medicine
Volume	61
Issue number	5
DOIs	https://doi.org/10.2967/jnumed.119.232363
State	Published - 2020
Externally published	Yes

Keywords

F-ISO-1
TMEM-97
breast cancer
proliferation
σ-2

Access to Document

10.2967/jnumed.119.232363

Cite this

McDonald, E. S., Doot, R. K., Young, A. J., Schubert, E. K., Tchou, J., Pryma, D. A., Farwell, M. D., Nayak, A., Ziober, A., Feldman, M. D., DeMichele, A., Clark, A. S., Shah, P. D., Lee, H., Carlin, S. D., Mach, R. H., & Mankoff, D. A. (2020). Breast Cancer ¹⁸F-ISO-1 Uptake as a Marker of Proliferation Status. Journal of Nuclear Medicine, 61(5), 665-670. https://doi.org/10.2967/jnumed.119.232363

@article{70f5d806d6a74af5b0b63c123101c8c1,

title = "Breast Cancer 18F-ISO-1 Uptake as a Marker of Proliferation Status",

abstract = "The σ2 receptor is a potential in vivo target for measuring proliferative status in cancer. The feasibility of using N-(4-(6, 7-dimethoxy-3, 4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbenzamide (18F-ISO-1) to image solid tumors in lymphoma, breast cancer, and head and neck cancer has been previously established. Here, we report the results of the first dedicated clinical trial of 18F-ISO-1 in women with primary breast cancer. Our study objective was to determine whether 18F-ISO-1 PET could provide an in vivo measure of tumor proliferative status, and we hypothesized that uptake would correlate with a tissue-based assay of proliferation, namely Ki-67 expression. Methods: Twenty-eight women with 29 primary invasive breast cancers were prospectively enrolled in a clinical trial (NCT 02284919) between March 2015 and January 2017. Each received an injection of 278–527 MBq of 18F-ISO-1 and then underwent PET/CT imaging of the breasts 50–55 min later. In vivo uptake of 18F-ISO-1 was quantitated by SUVmax and distribution volume ratios and was compared with ex vivo immunohistochemistry for Ki-67. Wilcoxon rank-sum tests assessed uptake differences across Ki-67 thresholds, and Spearman correlation tested associations between uptake and Ki-67. Results: Tumor SUVmax (median, 2.0 g/mL; range, 1.3–3.3 g/mL), partial-volume–corrected SUVmax, and SUV ratios were tested against Ki-67. Tumors stratified into the high–Ki-67 ($20%) group had SUVmax greater than the low–Ki-67 (, 20%) group (P 5 0.02). SUVmax exhibited a positive correlation with Ki-67 across all breast cancer subtypes (ρ 5 0.46, P 5 0.01, n 5 29). Partial-volume–corrected SUVmax was positively correlated with Ki-67 for invasive ductal carcinoma (ρ 5 0.51, P 5 0.02, n 5 21). Tumor–to–normal-tissue ratios and tumor distribution volume ratio did not correlate with Ki-67 (P . 0.05). Conclusion: 18F-ISO-1 uptake in breast cancer modestly correlates with an in vitro assay of proliferation.",

keywords = "F-ISO-1, TMEM-97, breast cancer, proliferation, σ-2",

author = "McDonald, {Elizabeth S.} and Doot, {Robert K.} and Young, {Anthony J.} and Schubert, {Erin K.} and Julia Tchou and Pryma, {Daniel A.} and Farwell, {Michael D.} and Anupma Nayak and Amy Ziober and Feldman, {Michael D.} and Angela DeMichele and Clark, {Amy S.} and Shah, {Payal D.} and Hsiaoju Lee and Carlin, {Sean D.} and Mach, {Robert H.} and Mankoff, {David A.}",

note = "Publisher Copyright: COPYRIGHT {\textcopyright} 2020 by the Society of Nuclear Medicine and Molecular Imaging.",

year = "2020",

doi = "10.2967/jnumed.119.232363",

language = "English",

volume = "61",

pages = "665--670",

journal = "Journal of Nuclear Medicine",

issn = "0161-5505",

publisher = "Society of Nuclear Medicine Inc.",

number = "5",

}

McDonald, ES, Doot, RK, Young, AJ, Schubert, EK, Tchou, J, Pryma, DA, Farwell, MD, Nayak, A, Ziober, A, Feldman, MD, DeMichele, A, Clark, AS, Shah, PD, Lee, H, Carlin, SD, Mach, RH & Mankoff, DA 2020, 'Breast Cancer ¹⁸F-ISO-1 Uptake as a Marker of Proliferation Status', Journal of Nuclear Medicine, vol. 61, no. 5, pp. 665-670. https://doi.org/10.2967/jnumed.119.232363

TY - JOUR

T1 - Breast Cancer 18F-ISO-1 Uptake as a Marker of Proliferation Status

AU - McDonald, Elizabeth S.

AU - Doot, Robert K.

AU - Young, Anthony J.

AU - Schubert, Erin K.

AU - Tchou, Julia

AU - Pryma, Daniel A.

AU - Farwell, Michael D.

AU - Nayak, Anupma

AU - Ziober, Amy

AU - Feldman, Michael D.

AU - DeMichele, Angela

AU - Clark, Amy S.

AU - Shah, Payal D.

AU - Lee, Hsiaoju

AU - Carlin, Sean D.

AU - Mach, Robert H.

AU - Mankoff, David A.

PY - 2020

Y1 - 2020

N2 - The σ2 receptor is a potential in vivo target for measuring proliferative status in cancer. The feasibility of using N-(4-(6, 7-dimethoxy-3, 4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbenzamide (18F-ISO-1) to image solid tumors in lymphoma, breast cancer, and head and neck cancer has been previously established. Here, we report the results of the first dedicated clinical trial of 18F-ISO-1 in women with primary breast cancer. Our study objective was to determine whether 18F-ISO-1 PET could provide an in vivo measure of tumor proliferative status, and we hypothesized that uptake would correlate with a tissue-based assay of proliferation, namely Ki-67 expression. Methods: Twenty-eight women with 29 primary invasive breast cancers were prospectively enrolled in a clinical trial (NCT 02284919) between March 2015 and January 2017. Each received an injection of 278–527 MBq of 18F-ISO-1 and then underwent PET/CT imaging of the breasts 50–55 min later. In vivo uptake of 18F-ISO-1 was quantitated by SUVmax and distribution volume ratios and was compared with ex vivo immunohistochemistry for Ki-67. Wilcoxon rank-sum tests assessed uptake differences across Ki-67 thresholds, and Spearman correlation tested associations between uptake and Ki-67. Results: Tumor SUVmax (median, 2.0 g/mL; range, 1.3–3.3 g/mL), partial-volume–corrected SUVmax, and SUV ratios were tested against Ki-67. Tumors stratified into the high–Ki-67 ($20%) group had SUVmax greater than the low–Ki-67 (, 20%) group (P 5 0.02). SUVmax exhibited a positive correlation with Ki-67 across all breast cancer subtypes (ρ 5 0.46, P 5 0.01, n 5 29). Partial-volume–corrected SUVmax was positively correlated with Ki-67 for invasive ductal carcinoma (ρ 5 0.51, P 5 0.02, n 5 21). Tumor–to–normal-tissue ratios and tumor distribution volume ratio did not correlate with Ki-67 (P . 0.05). Conclusion: 18F-ISO-1 uptake in breast cancer modestly correlates with an in vitro assay of proliferation.

AB - The σ2 receptor is a potential in vivo target for measuring proliferative status in cancer. The feasibility of using N-(4-(6, 7-dimethoxy-3, 4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbenzamide (18F-ISO-1) to image solid tumors in lymphoma, breast cancer, and head and neck cancer has been previously established. Here, we report the results of the first dedicated clinical trial of 18F-ISO-1 in women with primary breast cancer. Our study objective was to determine whether 18F-ISO-1 PET could provide an in vivo measure of tumor proliferative status, and we hypothesized that uptake would correlate with a tissue-based assay of proliferation, namely Ki-67 expression. Methods: Twenty-eight women with 29 primary invasive breast cancers were prospectively enrolled in a clinical trial (NCT 02284919) between March 2015 and January 2017. Each received an injection of 278–527 MBq of 18F-ISO-1 and then underwent PET/CT imaging of the breasts 50–55 min later. In vivo uptake of 18F-ISO-1 was quantitated by SUVmax and distribution volume ratios and was compared with ex vivo immunohistochemistry for Ki-67. Wilcoxon rank-sum tests assessed uptake differences across Ki-67 thresholds, and Spearman correlation tested associations between uptake and Ki-67. Results: Tumor SUVmax (median, 2.0 g/mL; range, 1.3–3.3 g/mL), partial-volume–corrected SUVmax, and SUV ratios were tested against Ki-67. Tumors stratified into the high–Ki-67 ($20%) group had SUVmax greater than the low–Ki-67 (, 20%) group (P 5 0.02). SUVmax exhibited a positive correlation with Ki-67 across all breast cancer subtypes (ρ 5 0.46, P 5 0.01, n 5 29). Partial-volume–corrected SUVmax was positively correlated with Ki-67 for invasive ductal carcinoma (ρ 5 0.51, P 5 0.02, n 5 21). Tumor–to–normal-tissue ratios and tumor distribution volume ratio did not correlate with Ki-67 (P . 0.05). Conclusion: 18F-ISO-1 uptake in breast cancer modestly correlates with an in vitro assay of proliferation.

KW - F-ISO-1

KW - TMEM-97

KW - breast cancer

KW - proliferation

KW - σ-2

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U2 - 10.2967/jnumed.119.232363

DO - 10.2967/jnumed.119.232363

M3 - Article

C2 - 31836680

AN - SCOPUS:85084960997

SN - 0161-5505

VL - 61

SP - 665

EP - 670

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

IS - 5