La PET/TAC con 18F-FDG en la evaluación de la respuesta de los tumores del estroma gastrointestinal al tratamiento con imatinib

Banzo, Ignacio; Quirce, R.; Martínez-Rodríguez, I.; Jiménez-Bonilla, J.; Sainz-Esteban, Aurora; Barragán, Jorge; Portilla-Quattrociocchi, H.; Carril, J.M.

doi:10.1157/13121026

Cited by 6 publications

(1 citation statement)

References 22 publications

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“…In the original clinical trial of imatinib in patients with chronic myeloid leukemia, 95% of patients showed a complete hematologic response and 94% of patients showed a complete cytogenetic remission of the disease (3). In contrast, most gastrointestinal stromal tumor cells have a mutation in the coding genes for KIT and in the PDGFRα domain; these mutations prompt the activation of c-Kit, which in turn results in increased tumor growth (4). …”

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confidence: 99%

In Vivo Imaging of Bcr-Abl Overexpressing Tumors with a Radiolabeled Imatinib Analog as an Imaging Surrogate for Imatinib

Glekas¹,

Pillarsetty²,

Punzalan³

et al. 2011

J Nucl Med

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Imatinib mesylate is a tyrosine kinase inhibitor that was approved by the U.S. Food and Drug Administration in 2001 for treatment of many different stages of chronic myeloid leukemia and in 2002 for treatment of gastrointestinal stromal tumors. Imatinib is known to inhibit the dysregulated proliferation of chronic myeloid leukemia, which is associated with the Bcr-Abl kinase; in gastrointestinal stromal tumors, imatinib is known to act via c-Kit kinase inhibition. The objective of this study was to synthesize an 18F-labeled analog of imatinib not as a primary imaging agent but rather as a tracer for in vivo drug distribution and tracer concentration that can be used as a PET imaging surrogate for imatinib. Methods Molecular modeling studies based on the crystal structure of imatinib bound to the active site of Abl were performed for designing the fluorinated analog. A 2-fluoroethyl analog of imatinib (SKI696) was synthesized using well-established procedures. The selectivity and binding affinity of SKI696 were compared with those of imatinib in vitro. Mice bearing K562 tumor xenografts, which are known to overexpress Bcr-Abl, were imaged with 18F-SKI696 PET. A biodistribution study was also performed on K562 tumor–bearing mice to which our radiolabeled tracer was administered. Results The kinase assay verified that imatinib and SKI696 bind to the same targets with similar affinities. The feasibility of using 18F-SKI696 as a PET agent was examined in vivo, and 18F-SKI696 PET was shown to visualize K562 tumor xenografts in nude mice. The tumor was visible on PET 1 h after injection, with uptake of 1% of the injected dose. Biodistribution studies in K562-bearing mice were also performed, and the uptake of 18F-SKI696 (percentage injected dose per gram) for each organ was calculated. Conclusion The results of the binding assay showed that SKI696 has selectivity and binding affinity comparable to imatinib. Small-animal PET of K562 tumor–bearing mice using 18F-SKI696 as a PET agent displayed promising tumor uptake and tumor-to-nontarget contrast. Because 18F-SKI696 has been taken up in vivo by tumors that overexpress Bcr-Abl, we are exploring a possible role for identifying tumors that will respond to imatinib before therapy.

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confidence: 99%