Preprint Epublish 1 citation
PubMed: 36778307 DOI: 10.1101/2023.02.03.526958
Combined multiphoton microscopy and somatostatin receptor type 2 imaging of pancreatic neuroendocrine tumors.
bioRxiv
Authors: Noelle Daigle, Thomas Knapp, Suzann Duan, David W Jones, Ali Azhdarinia, Sukhen C Ghosh, Solmaz AghaAmiri, Naruhiko Ikoma, Jeannelyn Estrella, Martin J Schnermann, Juanita L Merchant, Travis W Sawyer
Affiliations
- University of Arizona, Wyant College of Optical Sciences, 1630 E. University Blvd, Tucson, AZ, 85721, USA.
- University of Arizona, Department of Biomedical Engineering, 1127 E. James E. Rogers Way, Tucson, AZ, 85721, USA.
- University of Arizona, College of Medicine, 1515 N. Campbell Ave, Tucson, AZ, 85724, USA.
- The University of Texas Health Science Center at Houston, 7000 Fannin St, Houston, TX, 77030, USA.
- The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
- National Cancer Institute, 1050 Boyles St, Frederick, MD, 21702, USA.
Abstract
Pancreatic neuroendocrine tumors (PNETs) are a rare but increasingly more prevalent cancer with heterogeneous clinical and pathological presentation. Surgery is the preferred treatment for all hormone-expressing PNETs and any PNET greater than 2 cm, but difficulties arise when tumors are multifocal, metastatic, or small in size due to lack of effective surgical localization. Existing techniques such as intraoperative ultrasound provide poor contrast and resolution, resulting in low sensitivity for such tumors. Somatostatin receptor type 2 (SSTR2) is commonly overexpressed in PNETs and presents an avenue for targeted tumor localization. SSTR2 is often used for pre-operative imaging and therapeutic treatment, with recent studies demonstrating that somatostatin receptor imaging (SRI) can be applied in radioguided surgery to aid in removal of metastatic lymph nodes and achieving negative surgical margins. However not all PNETs express SSTR2, indicating labeled SRI could benefit from using a supplemental label-free technique such as multiphoton microscopy (MPM), which has proven useful in improving the accuracy of diagnosing more common exocrine pancreatic cancers. Our work tests the suitability of combined SRI and MPM for localizing PNETs by imaging and comparing samples of PNETs and normal pancreatic tissue. Specimens were labeled with a novel SSTR2-targeted contrast agent and imaged using fluorescence microscopy, and subsequently imaged using MPM to collect four autofluorescent channels and second harmonic generation. Our results show that a combination of both SRI and MPM provides enhanced contrast and sensitivity for localizing diseased tissue, suggesting that this approach could be a valuable clinical tool for surgical localization and treatment of PNETs.
MeSH
Multimodal Imaging, Therapeutics, Receptors, Somatostatin, Neuroendocrine Tumors, Neoplasms, Microscopy, Fluorescence, Neuroectodermal Tumors, Primitive, Tissues, Margins Of Excision