Abstract
The sigma-2 receptor is a potential in vivo target for measuring proliferative status in cancer. Dehdashti et al. established 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 (1). Here we report 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 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 3/2015 and 1/2017. Each received an injection of 278-527 MBq 18F-ISO-1 followed by a 50-55 minute post-injection positron emission tomography-computed tomography (PET/CT) image of the breasts. In vivo uptake of 18F-ISO-1 was quantitated by maximum standardized uptake values (SUVmax) and distribution volume ratios (DVR) and was compared to ex vivo immunohistochemistry for Ki-67. Wilcoxon rank-sum test assessed uptake differences across Ki-67 thresholds and Spearman’s 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 (PVC) 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 = 0.02). SUVmax exhibited a positive correlation with Ki-67 across all breast cancer subtypes (ρ=0.46, P = 0.01, n = 29). PVC 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 DVR 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.
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