Imaging of Delayed-Type Hypersensitivity Reaction by PET and 18F-Galacto-RGD

Journal of Nuclear Medicine

Markus Schwaiger¹  Martin Röcken¹  Roland Haubner¹  Wolfgang A. Weber¹  Heidi Braumüller¹  Manfred Kneilling¹  Bernd J. Pichler¹ 

关键词: autoradiography;    molecular imaging;    PET;    radiopharmaceuticals;    animal imaging;    inflammation;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Radiolabeled cyclic peptides containing the amino acid sequence arginine-glycine-aspartate (RGD peptides) have successfully been used to image the expression of the αvβ3 integrin in malignant tumors. However, the αvβ3 integrin also plays an important role in angiogenesis induced by chronic inflammatory processes. Therefore, the aim of this study was to evaluate whether radiolabeled RGD peptides may also be used to assess αvβ3 expression in inflammatory diseases. We studied a hapten-induced delayed-type hypersensitivity reaction (DTHR) as a model for inflammatory processes, since DTHRs are involved in many human autoimmune disorders. Methods: The abdominal skin of mice was sensitized by application of 2,4,6-trinitrochlorobenzene (TNCB). One week later, a DTHR was elicited by challenging the right ear with TNCB. Application of TNCB was then repeated every 48 h to induce chronic skin inflammation. Small-animal PET and autoradiography with the αvβ3 ligands 18F-galacto-RGD and 125I-gluco-RGD were performed at various times after TNCB application. The time course of tracer uptake by the treated ears was compared with histologic skin changes. Results: The first challenge with TNCB caused, within 12 h, an acute inflammatory response with dense dermal infiltrates of polymorphonuclear leukocytes and lymphocytes. However, autoradiography revealed no significant increase in 125I-gluco-RGD uptake at that time (mean uptake ratio for treated ear to untreated ear, 1.02 ± 0.1 [SD]). Further challenges with TNCB resulted in chronic skin inflammation with markedly increased small-vessel density in the ear tissue. This was paralleled by a continuous increase in uptake of 125I-gluco-RGD. After 13 challenges, the uptake ratio had increased to 2.30 ± 0.27 (P < 0.005 compared with baseline). Enhanced uptake of radiolabeled RGD peptides in chronic inflammation was also demonstrated noninvasively by PET with 18F-galacto-RGD. Pretreatment of the mice with nonradiolabeled cyclic peptide c(RGDfV) almost completely blocked uptake of 18F-galacto-RGD by the challenged ear, thus confirming the specificity of tracer uptake. Conclusion: Radiolabeled RGD peptides allow a noninvasive assessment of αvβ3 expression in inflammatory processes. PET with 18F-galacto-RGD might become a powerful tool to distinguish between the acute and chronic phases of T cell–mediated immune responses and may represent a new biomarker for disease activity in autoimmune disorders.

【 授权许可】

Unknown