Abstract
2592
Introduction: Invasive lobular breast cancer (ILC) has a distinct histology and discohesive growth which makes it difficult to visualize with conventional imaging (CI), including fluorodeoxyglucose (FDG) positron emission tomography (PET). In prior reports from our institutions amino-acid transport imaging using 18F-fluciclovine PET showed promise in detection of ILC (J Nucl Med 2016;57(9):1350 and J Nucl Med 2016; 57(9):1357). Prostate specific membrane antigen (PSMA) PET has also been proposed to detect ILC due to the upregulation of PSMA receptors in tumor angiogenesis. We are conducting an NIH funded trial (R21CA256280; NCT04750473) in which both 18F-fluciclovine and 68Ga-PSMA-11 are performed in patients with locally advanced or metastatic ILC to determine if either radiotracer has value in the detection of metastatic ILC.
Methods: Patients with treatment-naïve or previously treated ILC who are not currently on systemic therapy (> 4 weeks since last systemic therapy if received previously) and who have either: a) no known metastasis but clinical or imaging suspicion of metastatic disease; b) biopsy proven metastatic disease but suspicion of a greater tumor burden than detected by CI, are eligible for inclusion. All patients will have undergone standard of care CI at the oncologist’s discretion. Patients first undergo PET/ computed tomography (CT) from skull base to thigh 1 hour after IV injection of 5 mCi 68Ga-PSMA-11. Twenty-four hours later, the patient undergoes similar PET/CT 4 min after IV injection of 10 mCi 18F-fluciclovine. Images are first blindly interpreted by three readers who then render a consensus interpretation. Patients also have blood drawn for future circulating tumor DNA mutation analysis including PIK3CA, ESR1, HER2, and AKT1.
Results: Six patients have been studied to date (accrual goal 20). All patients had ER positive and HER2 negative breast cancer. Four patients were concordantly negative on both PET scans; 1 patient had discordant findings with positive 18F-fluciclovine and negative 68Ga-PSMA; 1 patient was concordantly positive on both studies.
The discordant patient (figure 1) had proven metastasis on endoscopic biopsy of the gastric antrum and surgical biopsy of a peritoneal implant during gastrojejunostomy approximately 1 year earlier and was in the process of switching systemic therapy due to clinical progression. CT scan 2 weeks prior to PET was unrevealing except for known treated sclerotic osseous metastases. Research PET scans demonstrated extensive 18F-fluciclovine positive and 68Ga-PSMA negative mediastinal, internal mammary, retroperitoneal, and pelvic adenopathy, breast and active skeletal lesions, as well as peritoneal implants. The most intense uptake was in an L1 vertebral body with an SUVmax of 8.6 and in retroperitoneal nodal disease with SUVmax of 8.1.
The concordant positive patient (figure 2) had biopsy proven skeletal metastasis with rising cancer antigens (CA) 27.29 and CA15.3 despite systemic therapy with fulvestrant/Ibrance which was then stopped. FDG PET 50 days before research PET did not reveal active lesions, but multiple lesions were present on 18F-fluciclovine and 68Ga-PSMA-11 PET with most intense activity at S1 with SUVmax of 7.3 on 18F-fluciclovine and 4.0 on 68Ga-PSMA-11. Yet, target to background was higher with 68Ga-PSMA-11 due to lower adjacent marrow background with 68Ga-PSMA-11. Progressive skeletal disease was correlated with magnetic resonance imaging 7 days after research PET.
Other confirmatory procedures for both positive cases are pending.
Conclusions: Interim analysis demonstrates the potential utility of 18F-fluciclovine and 68Ga-PSMA-11 PET in visualizing active ILC, not appreciated on CI. Complete accrual and comprehensive analysis are required before more definitive conclusions may be made.
Study funded by NIH R21CA256280. Fluciclovine doses provided by Blue Earth Diagnostics, Inc. Ga-PSMA-11 cold kits provided by Telix Pharmaceuticals (US) Inc.
