PT - JOURNAL ARTICLE AU - Biegon, Anat AU - Shroyer, Kenneth R. AU - Franceschi, Dinko AU - Dhawan, Jasbeer AU - Tahmi, Mouna AU - Pareto, Deborah AU - Bonilla, Patrick AU - Airola, Krystal AU - Cohen, Jules TI - Initial studies with [<sup>11</sup>C]vorozole positron emission tomography detect over-expression of intra-tumoral aromatase in breast cancer AID - 10.2967/jnumed.119.231589 DP - 2019 Nov 01 TA - Journal of Nuclear Medicine PG - jnumed.119.231589 4099 - http://jnm.snmjournals.org/content/early/2019/11/21/jnumed.119.231589.short 4100 - http://jnm.snmjournals.org/content/early/2019/11/21/jnumed.119.231589.full AB - Introduction: Aromatase inhibitors are the mainstay of hormonal therapy in estrogen receptor positive, postmenopausal breast cancer, although response rate is just over 50%. The goal of the present study was to validate and optimize positron emission tomography (PET) with 11C-vorozole for measuring aromatase expression in postmenopausal breast cancer. Methods: Ten newly diagnosed, postmenopausal women with biopsy confirmed breast cancer were administered 11C-vorozole intravenously and PET emission data collected between 40 – 90 minutes post-injection. Tracer injection and scanning were repeated 2 hours after ingestion of 2.5mg letrozole p.o. Mean and maximal standard uptake values and ratios to non-tumor tissue (SUVs, SUVRs) were calculated for tumor and non-tumor regions at baseline and after letrozole. Biopsy specimens from the same tumors were stained for aromatase using immunohistochemistry and evaluated for stain intensity and the percentage of immune-positive cells. Results: Seven of the 10 women (70%) demonstrated increased focal uptake of tracer (SUVR&gt;1.1) coinciding with the mammographic location of the lesion. The other 3 women (30%) did not show increased uptake in the tumor (SUVR &lt;1.0). All of the cases with SUVR above 1.1 had SUVs above 2.4 and there was no overlap in SUV between the two groups, with mean SUV in tumors overexpressing aromatase (SUVR&gt;1.1) ranging from 2.47 to 13.6, while tumors not overexpressing aromatase (SUVR&lt;1) ranged from 0.8 to 1.8. Pretreatment with letrozole reduced tracer uptake in the majority of subjects; although the %blocking varied across and within tumors. Tumors with high SUV in vivo also showed high staining intensity on IHC. Conclusion: PET with 11C-vorozole is a useful technique for measuring aromatase expression in individual breast lesions, enabling a non-invasive quantitative measurement of baseline and post-treatment aromatase availability in primary tumors and metastatic lesions.