2. Academic Validation
  3. Breast Cancer 18F-ISO-1 Uptake as a Marker of Proliferation Status

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

  • J Nucl Med. 2020 May;61(5):665-670. doi: 10.2967/jnumed.119.232363.
Elizabeth S McDonald 1,  Robert K Doot 2,  Anthony J Young 2,  Erin K Schubert 2,  Julia Tchou 3,  Daniel A Pryma 2,  Michael D Farwell 2,  Anupma Nayak 4,  Amy Ziober 4,  Michael D Feldman 4,  Angela DeMichele 5,  Amy S Clark 5,  Payal D Shah 5,  Hsiaoju Lee 2,  Sean D Carlin 2,  Robert H Mach 2,  David A Mankoff 2
Affiliations

Affiliations

  • 1 Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania [email protected].
  • 2 Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • 3 Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • 4 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and.
  • 5 Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
PMID: 31836680 DOI: 10.2967/jnumed.119.232363
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 (NCT02284919) 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 = 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 > 0.05). Conclusion:18F-ISO-1 uptake in breast Cancer modestly correlates with an in vitro assay of proliferation.

Keywords

18F-ISO-1; TMEM-97, proliferation; breast cancer; σ-2.

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