Prospective investigation of amino acid transport and PSMA-targeted positron emission tomography for metastatic lobular breast carcinoma

Eur J Nucl Med Mol Imaging. 2024 Nov;51(13):4073-4082. doi: 10.1007/s00259-024-06830-7. Epub 2024 Jul 8.

Abstract

Purpose: To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or 18F-FDG positron-emission-tomography (PET)-CT].

Methods: 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with 18F-fluciclovine and 68Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and 18F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of 18F-fluciclovine and 68Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test.

Results: The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. 68Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. 18F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for 18F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between 68Ga-PSMA-11 and standard-of care imaging. 18F-fluciclovine cDR was also significantly higher than 68Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with 18F-fluciclovine (n = 18) was significantly greater than for 68Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021].

Conclusion: In this exploratory trial, 18F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to 68Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with 18F-fluciclovine than for 68Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study.

Clinical trial registration: Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280).

Keywords: 18F-Fluciclovine; 68Ga-PSMA-11; Detection rate; Lobular breast cancer; PET-CT.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Amino Acids
  • Antigens, Surface / metabolism
  • Biological Transport
  • Breast Neoplasms* / diagnostic imaging
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Carboxylic Acids*
  • Carcinoma, Lobular* / diagnostic imaging
  • Carcinoma, Lobular* / metabolism
  • Carcinoma, Lobular* / secondary
  • Cyclobutanes*
  • Edetic Acid / analogs & derivatives
  • Female
  • Gallium Isotopes*
  • Gallium Radioisotopes*
  • Glutamate Carboxypeptidase II / metabolism
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Oligopeptides
  • Positron Emission Tomography Computed Tomography* / methods
  • Prospective Studies

Substances

  • Amino Acids
  • Antigens, Surface
  • Carboxylic Acids
  • Cyclobutanes
  • Edetic Acid
  • fluciclovine F-18
  • FOLH1 protein, human
  • gallium 68 PSMA-11
  • Gallium Isotopes
  • Gallium Radioisotopes
  • Glutamate Carboxypeptidase II
  • Oligopeptides

Associated data

  • ClinicalTrials.gov/NCT04750473