Thyroid cancer imaging in vivo by targeting the anti-apoptotic molecule galectin-3.
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.
Bartolazzi
Armando
A
Cellular and Molecular Tumor Pathology Laboratory, Cancer Center Karolinska, Karolinska Hospital, Stockholm, Sweden. Armando.Bartolazzi@ki.se
D'Alessandria
Calogero
C
Parisella
Maria Gemma
MG
Signore
Alberto
A
Del Prete
Fabrizio
F
Lavra
Luca
L
Braesch-Andersen
Sten
S
Massari
Roberto
R
Trotta
Carlo
C
Soluri
Alessandro
A
Sciacchitano
Salvatore
S
Scopinaro
Francesco
F
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*
D000911:Antibodies, Monoclonal; D037502:Galectin 3