Intraoperative Tumor Detection Using a Ratiometric Activatable Fluorescent Peptide: A First-in-Human Phase 1 Study

Ann Surg Oncol. 2017 Oct;24(11):3167-3173. doi: 10.1245/s10434-017-5991-3. Epub 2017 Jul 11.


Background: Positive surgical margins remain a significant challenge in breast cancer surgery. This report describes the use of a novel, first-in-human ratiometric activatable cell-penetrating peptide in breast cancer surgery.

Methods: A two-part, multi-institutional phase 1 trial of AVB-620 with a 3+3 dose escalation and dose-expansion cohorts was conducted. The patients received an infusion of AVB-620 2-20 h before planned lumpectomy/mastectomy and sentinel node biopsy/axillary dissection. Imaging analysis was performed on images obtained from the surgical field as well as post-excision surgical specimens. Pathology reports were obtained to correlate imaging results with histopathologic data. Information on physical adverse events and laboratory abnormalities were recorded.

Results: A total of 27 patients received infusion of AVB-620 and underwent surgical excision of breast cancer. The findings showed no adverse events or laboratory values attributable to infusion of AVB-620. The 8-mg dose was selected from the dose-escalation cohort for use with the expansion cohort based on imaging data. Region-of-interest (ROI) imaging analysis from the 8-mg cohort demonstrated measurable changes between pathology confirmed tumor-positive and tumor-negative tissue.

Conclusion: Intraoperative imaging of surgical specimens after infusion with AVB-620 allowed for real-time tumor detection. Infusion of AVB-620 is safe and may improve intraoperative detection of malignant tissue during breast cancer operations.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / diagnostic imaging
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / surgery
  • Carcinoma, Lobular / diagnosis
  • Carcinoma, Lobular / diagnostic imaging
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / surgery
  • Cell-Penetrating Peptides / metabolism*
  • Cohort Studies
  • Female
  • Fluorescence*
  • Follow-Up Studies
  • Humans
  • Intraoperative Care
  • Mastectomy*
  • Middle Aged
  • Molecular Imaging / methods*
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Surgery, Computer-Assisted / methods*
  • Survival Rate


  • Cell-Penetrating Peptides
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2