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

Abstract

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.

• Authors: Jonathan T Unkart, Steven L Chen, Irene L Wapnir, Jesús E González, Alec Harootunian, Anne M Wallace
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 24 Issue 11 Pg. 3167-3173 (Oct 2017) ISSN: 1534-4681 [Electronic] United States
• PMID: 28699134 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)

Chemical References

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

Topics

• Adult
• Aged
• Breast Neoplasms (diagnosis, diagnostic imaging, metabolism, surgery)
• Carcinoma, Ductal, Breast (diagnosis, diagnostic imaging, metabolism, surgery)
• Carcinoma, Lobular (diagnosis, diagnostic imaging, metabolism, 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