Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide

Abstract

Context.— Resection of breast carcinoma with adequate margins reduces the risk of local recurrence and reoperation. Tozuleristide (BLZ-100) is an investigational peptide-fluorophore agent that may aid in intraoperative tumor detection and margin assessment. In this study, fluorescence imaging was conducted ex vivo on gross breast pathology specimens. Objectives.— To determine the potential of tozuleristide to detect breast carcinoma in fresh pathology specimens and the feasibility of fluorescence-guided intraoperative pathology assessment of surgical margins. Design.— Twenty-three patients received an intravenous bolus dose of 6 or 12 mg of tozuleristide at least 1 hour before surgery. Fifteen lumpectomy and 12 mastectomy specimens were evaluated for fluorescence by the site's clinical pathology staff using the SIRIS, an investigational near-infrared imaging device. The breast tissue was then processed per usual procedures. Fluorescent patterns were correlated with the corresponding hematoxylin-eosin–stained sections. Clinical pathology reports were used to correlate fluorescent signal to grade, histotype, prognostic marker status, and margin measurements. Results.— Tozuleristide fluorescence was readily observed in invasive and in situ breast carcinoma specimens. Most invasive carcinomas were bright and focal, whereas in situ lesions demonstrated a less intense, more diffuse pattern. Tozuleristide was detected in ductal and lobular carcinomas with a similar fluorescent pattern. Fluorescence was detected in high- and low-grade lesions, and molecular marker/hormone receptor status did not affect signal. Fluorescence could be used to identify the relationship of carcinoma to margins intraoperatively. Conclusions.— Tumor targeting with tozuleristide allowed visual real-time distinction between pathologically confirmed breast carcinoma and normal tissue.

A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients

“…The ability to serially image the cutaneous lesions provided data regarding signal and contrast durability. These data were important in the design of subsequent clinical trials with BLZ-100, which demonstrated efficacy with dosing the day before or day of surgery in CNS [ 11 ] or non-CNS [ 10 ] tumors. A Phase II/III study in pediatric CNS tumors is ongoing.…”

“…BLZ-100 was well-tolerated in definitive toxicology and safety pharmacology studies in rats and non-human primates [ 9 ]. The BLZ-100 Phase 1 clinical development program has included studies in adult glioma (NCT02234297), pediatric CNS tumors (NCT02462629), and breast cancer [ 10 ] and other solid tumors (NCT02496065). The results from Phase I adult glioma have been published in 2020 [ 11 ].…”

Receptor-Targeted Fluorescence-Guided Surgery With Low Molecular Weight Agents

“…Breast carcinoma : BLZ-100 has also been evaluated in breast cancer for fluorescence-guided pathology ( 50 ). The objective of this study was to investigate the feasibility of using BLZ-100 to (i) target breast carcinoma and (ii) enable demarcation of surgical margins.…”

Emerging Fluorescent Molecular Tracers to Guide Intra-Operative Surgical Decision-Making

“…The knottin peptide Tozuleristide, which consists of the scorpion venom derived ligand chlorotoxin conjugated to ICG, is currently undergoing clinical translation. This probe was able to distinguish tumor from normal tissue in resected human breast cancer specimens between 1 and 26 h post-injection (Dintzis et al, 2018). Tozuleristide is a naturally occurring knottin, whose exact specificity is not fully known, though MMP-2 and AnnexinA2 have been observed as targets.…”