PET/CT Imaging with an ¹⁸F-Labeled Galactodendritic Unit in a Galectin-1–Overexpressing Orthotopic Bladder Cancer Model

Abstract

Galectins are carbohydrate-binding proteins overexpressed in bladder cancer (BCa) cells. Dendritic galactose moieties have a high affinity for galectin-expressing tumor cells. We radiolabeled a dendritic galactose carbohydrate with fluorine-18-18 F-labeled galactodendritic unit 4-and examined its potential in imaging urothelial malignancies. Methods: The 18 F-labeled 1 st generation galactodendritic unit 4 was obtained from its tosylate precursor. We conducted in vivo studies in galectin-expressing UMUC3 orthotopic BCa model to determine the ability of 18 F-labeled galactodendritic unit 4 to image BCa. Results: Intravesical administration of 18 F-labeled galactodendritic unit 4 allowed specific accumulation of the carbohydrate radiotracer in galectin-1 overexpressing UMUC3 orthotopic tumors when imaged with PET. The 18 F-labeled galactodendritic unit 4 was not found to accumulate in non-tumor murine bladders. Conclusion: The 18 F-labeled galactodendritic unit 4 and similar analogs may be clinically relevant and exploitable for PET imaging of galectin-1 overexpressing bladder tumors.

Non-Invasive Imaging Modalities in Intravesical Murine Models of Bladder Cancer

“…The mean BCa tumor detection time in a syngeneic orthotopic model using MUI was found to be 10 days, ranging from 8 to 17 days, whereas that for the clinical symptoms of BCa was 20.8 days, ranging from 14 to 28 days [ 21 , 40 , 43 ]. Subsequent studies were able to detect orthotopic BCa tumors as early as 4 [ 39 ], 7 [ 47 ] and 11 days [ 38 , 40 , 48 ], which did not appear to be influenced by the cell line or mouse strain. Conversely, a more recent study was unable to detect tumors in a syngeneic orthotopic model until the thirteenth day and mice began to die on the sixteenth day from clinical symptoms [ 44 ].…”

“…Concurrently, Pereira et al [ 47 ] investigated the efficacy of using galectin-targeted imaging in an orthotopic xenograft model. Following one hour of the intravesical administration of 18 F-labeled galactodendritic unit 4, accumulation was significantly higher in BCa tumor-bearing mice compared to non-tumor bearing mice, with SUV mean values of 43.5 ± 4.2 and 2.0 ± 0.4, respectively [ 47 ]. These findings demonstrate the selectivity of galectin-targeted radiotracers in imaging intravesical BCa cells.…”