TY - JOUR T1 - Breast Cancer <sup>18</sup>F-ISO-1 Uptake as a Marker of Proliferation Status JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 665 LP - 670 DO - 10.2967/jnumed.119.232363 VL - 61 IS - 5 AU - Elizabeth S. McDonald AU - Robert K. Doot AU - Anthony J. Young AU - Erin K. Schubert AU - Julia Tchou AU - Daniel A. Pryma AU - Michael D. Farwell AU - Anupma Nayak AU - Amy Ziober AU - Michael D. Feldman AU - Angela DeMichele AU - Amy S. Clark AU - Payal D. Shah AU - Hsiaoju Lee AU - Sean D. Carlin AU - Robert H. Mach AU - David A. Mankoff Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/5/665.abstract 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 (&lt;20%) group (P = 0.02). SUVmax exhibited a positive correlation with Ki-67 across all breast cancer subtypes (ρ = 0.46, P = 0.01, n = 29). Partial-volume–corrected SUVmax was positively correlated with Ki-67 for invasive ductal carcinoma (ρ = 0.51, P = 0.02, n = 21). Tumor–to–normal-tissue ratios and tumor distribution volume ratio did not correlate with Ki-67 (P &gt; 0.05). Conclusion: 18F-ISO-1 uptake in breast cancer modestly correlates with an in vitro assay of proliferation. ER -