Fluorescently labeled peptides have the potential to make a positive impact on image-guided surgery and disease diagnosis. A technique of increasing interest involves the use of fluorescent peptide probes that bind or become modified by a molecular target overexpressed at the disease site. In the area of oncology, several fluorescently labeled peptides are already in the clinical stages of development as shown in Table 1.
Phase III Candidates
Avelas Biosciences is developing AVB620 as a real-time surgical diagnostic agent for breast cancer. AVB620 is a fluorescent protease-activated peptide that detects, marks, and diagnoses cancer. The product utilizes cell-penetrating peptides to deliver a fluorescent marker specifically to cancer cells. AVB620 is administered by intravenous injection before surgery and imaging is performed with a fluorescence-imaging camera to identify critical cancer margins and stage lymph nodes (1). In 2018, Avelas presented initial results from the first part of a Phase II clinical trial of AVB620 that demonstrated the potential of using AVB620 during surgery to identify malignant tissue and lymph nodes (2).
BLZ-100 (tozuleristide) is being developed by Blaze Bioscience for use as an imaging agent during cancer surgery for a range of cancer types including brain, breast, prostate, lung, colorectal, skin cancer, and sarcomas. BLZ-100 is used to “paint” tumors in order to guide surgeons during cancer removal. The tumor paint consists of chlorotoxin, a tumor penetrating peptide, conjugated to indocyanine green dye. In April 2016, Blaze completed a Phase I study of BLZ-100 in adult subjects with glioma undergoing surgery (3). BLZ-100 is currently being evaluated in a Phase II/III clinical study in pediatric central nervous system tumors (4).
Phase II Candidate
Edinburgh Molecular Imaging has developed a fluorescent optical imaging agent, EMI-137, that specifically targets the biomarker c-Met. The tracer is a small peptide labeled with a fluorophore. In 2017, Edinburgh Molecular Imaging announced that it initiated a Phase IIb clinical trial of EMI-137 in patients with suspected colorectal cancer (5).
Phase I Candidates
Dartmouth is collaborating with Affibody AB, LI-COR Biosciences, and the University of Alabama at Birmingham (UAB) Vector Production Facility to develop ABY-029, a fluorescence imaging and contrast agent for the detection of tumor cells during surgery. ABY-029 binds to cancer cell receptors and highlights tumors (6). The product is an IRDye® 800CW Maleimide labeled Affibody peptide. Dartmouth currently has three clinical trials of ABY-029 waiting for approval from the U.S. Food and Drug Administration of eIND amendments (7) (8) (9).
KCC Peptide contains seven amino acids and is attached to FITC (Fluorescein isothiocyanate). Researchers at the University of Michigan are developing KCC Peptide for use during colonoscopy procedures. The team’s technique involves spraying the fluorescent peptide onto the colon during colonoscopy so that the peptide will illuminate any abnormal or pre-cancerous areas when a special light is used in the scope. In 2016, the University of Michigan completed a Phase Ib study with KCC Peptide to determine if the peptide glows sufficiently (10).
The University of Michigan is also developing KSP-910638G, a fluorescently labeled peptide that consists of a heptapeptide attached via a five amino acid linker to a near-infrared fluorophore, IRDye® 800CW. This peptide is specific for human epithelial growth factor receptor 2 (HER2) (11). In 2019, the University of Michigan completed a Phase I study of KSP-910638G for detection of Barrett’s neoplasia in the esophagus (12).
LS301 is being developed by Washington University School of Medicine for use in fluorescence-guided cancer surgery. LS301 consists of a near-infrared fluorescent dye called cypate and a D-cysteine containing cyclic octapeptide. The peptide component of LS301 targets and binds integrin receptors expressed on tumor cells. A Phase I clinical trial is planned that will use LS301 during partial mastectomy and sentinel lymph node biopsy for breast cancer in order to evaluate LS301 uptake in tumors (13). In addition, a Phase I study is planned to evaluate LS301 uptake in patients undergoing liver, pancreas, or gastric surgery (14).
In addition, the University of Michigan is recruiting participants for a Phase I study of QRH-882260 Heptapeptide, a peptide attached via a five amino acid linker to the near-infrared fluorophore Cy5. The study will test the safety and efficacy of administering QRH-882260 Heptapeptide to patients undergoing clinically indicated endoscopic retrograde cholangiopancreatography (ERCP) for the evaluation of biliary disorders (15).
Fluorescently labeled peptides are valuable tools for molecular imaging and over the past decade, more fluorescent peptide probes have been entering clinical trials. To support the development of labeled peptides for research and clinical applications, Bachem provides a one-stop shop for the custom synthesis service of labeled peptides and amino acids. For custom synthesis, please contact our Custom Synthesis team to request a quote for your labeled peptide or amino acid.
1) AVB-620, Avelas Biosciences (2017)
2) Avelas Biosciences Presents Phase II, Period 1 Data in Poster Session at San Antonio Breast Cancer Symposium, Avelas Biosciences (2018)
3) Medtrack (2017)
4) Study of Tozuleristide and the Canvas Imaging System in Pediatric Subjects With CNS Tumors Undergoing Surgery, ClinicalTrials.gov (2019)
5) Edinburgh Molecular Imaging Commences Phase II European Cancer Trial, Edinburgh Molecular Imaging (2017)
6) Dartmouth Wins FDA Approval for Aid to Guide Cancer Surgery, Dartmouth News (2017)
7) A Microdose Evaluation Study of ABY-029 in Recurrent Glioma (ABY-029), ClinicalTrials.gov (2019)
8) A Microdose Evaluation Study of ABY-029 in Primary Sarcoma, ClinicalTrials.gov (2019)
9) A Microdose Evaluation Study of ABY-029 in Head and Neck Oncology Surgery, ClinicalTrials.gov (2019)
10) Study of KCC Peptide Application in the Colon, ClinicalTrials.gov (2017)
11) NCI Drug Dictionary, National Cancer Institute (2019)
12) Study of Multiplexed Heptapeptides for Detection of Neoplasia in the Esophagus, ClinicalTrials.gov (2019)
13) Real-time Intraoperative Breast Cancer Visualization for Margin Assessment, ClinicalTrials.gov (2019)
14) LS301 Uptake in Tumors of Patients Undergoing Liver, Pancreas, or Gastric Surgery, ClinicalTrials.gov (2019)
15) Fluorescence QRH-882260 Peptide Imaging in the Bile Duct, ClinicalTrials.gov (2018)