title: Thyroid cancer imaging in vivo by targeting the anti-apoptotic molecule galectin-3.
abstract: BACKGROUND
  The prevalence of thyroid nodules increases with age, average 4-7% for the U.S.A. adult population, but it is much higher (19-67%) when sub-clinical nodules are considered. About 90% of these lesions are benign and a reliable approach to their preoperative characterization is necessary. Unfortunately conventional thyroid scintigraphy does not allow the distinction among benign and malignant thyroid proliferations but it provides only functional information (cold or hot nodules). The expression of the anti-apoptotic molecule galectin-3 is restricted to cancer cells and this feature has potential diagnostic and therapeutic implications. We show here the possibility to obtain thyroid cancer imaging in vivo by targeting galectin-3.
  
  
  METHODS
  The galectin-3 based thyroid immuno-scintigraphy uses as radiotracer a specific (99m)Tc-radiolabeled mAb. A position-sensitive high-resolution mini-gamma camera was used as imaging capture device. Human galectin-3 positive thyroid cancer xenografts (ARO) and galectin-3 knockout tumors were used as targets in different experiments in vivo. 38 mice with tumor mass of about 1 gm were injected in the tail vein with 100 microCi of (99m)Tc-labeled mAb to galectin-3 (30 microg protein/in 100 microl saline solution). Tumor images were acquired at 1 hr, 3 hrs, 6 hrs, 9 hrs and 24 hrs post injection by using the mini-gamma camera.
  
  
  RESULTS
  Results from different consecutive experiments show an optimal visualization of thyroid cancer xenografts between 6 and 9 hours from injection of the radiotracer. Galectin-3 negative tumors were not detected at all. At 6 hrs post-injection galectin-3 expressing tumors were correctly visualized, while the whole-body activity had essentially cleared.
  
  
  CONCLUSIONS
  These results demonstrate the possibility to distinguish preoperatively benign from malignant thyroid nodules by using a specific galectin-3 radio-immunotargeting. In vivo imaging of thyroid cancer may allow a better selection of patients referred to surgery. The possibility to apply this method for imaging and treatment of other galectin-3 expressing tumors is also discussed.
authors.affiliation: Cellular and Molecular Tumor Pathology Laboratory, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden. Armando.Bartolazzi@ki.se
authors.forename: Armando
authors.initials: A
authors.lastname: Bartolazzi
authors.forename: Calogero
authors.initials: C
authors.lastname: D'Alessandria
authors.forename: Maria Gemma
authors.initials: MG
authors.lastname: Parisella
authors.forename: Alberto
authors.initials: A
authors.lastname: Signore
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Del Prete
authors.forename: Luca
authors.initials: L
authors.lastname: Lavra
authors.forename: Sten
authors.initials: S
authors.lastname: Braesch-Andersen
authors.forename: Roberto
authors.initials: R
authors.lastname: Massari
authors.forename: Carlo
authors.initials: C
authors.lastname: Trotta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Soluri
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sciacchitano
authors.forename: Francesco
authors.initials: F
authors.lastname: Scopinaro
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D017209:Apoptosis; D003952:Diagnostic Imaging / Q000295:instrumentation / Q000379:methods; D037502:Galectin 3 / Q000378:metabolism*; D015902:Gamma Cameras; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034622:RNA Interference; D011877:Radionuclide Imaging; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D037502:Galectin 3