Imaging of delayed-type hypersensitivity reaction by PET and 18F-galacto-RGD.

نویسندگان

  • Bernd J Pichler
  • Manfred Kneilling
  • Roland Haubner
  • Heidi Braumüller
  • Markus Schwaiger
  • Martin Röcken
  • Wolfgang A Weber
چکیده

UNLABELLED Radiolabeled cyclic peptides containing the amino acid sequence arginine-glycine-aspartate (RGD peptides) have successfully been used to image the expression of the alpha(v)beta(3) integrin in malignant tumors. However, the alpha(v)beta(3) 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 alpha(v)beta(3) 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 alpha(v)beta(3) ligands (18)F-galacto-RGD and (125)I-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 (125)I-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 (125)I-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 (18)F-galacto-RGD. Pretreatment of the mice with nonradiolabeled cyclic peptide c(RGDfV) almost completely blocked uptake of (18)F-galacto-RGD by the challenged ear, thus confirming the specificity of tracer uptake. CONCLUSION Radiolabeled RGD peptides allow a noninvasive assessment of alpha(v)beta(3) expression in inflammatory processes. PET with (18)F-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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Patterns of avb3 Expression in Primary and Metastatic Human Breast Cancer as Shown by 18F-Galacto-RGD PET

The integrin avb3 is a key player in angiogenesis and metastasis. Our aim was to study the uptake patterns of the avb3-selective PET tracer 18F-galacto-RGD in invasive ductal breast cancer. Methods: Sixteen patients with primary (n 5 12) or metastasized breast cancer (n 5 4) were examined with 18F-galacto-RGD PET. Standardized uptake values (SUVs) were derived by region-ofinterest analysis, and...

متن کامل

Non-invasive assessment of inter-and intrapatient variability of integrin expression in metastasized prostate cancer by PET

PURPOSE Due to the high expression of the integrin αvβ3 not only on endothelial cells, but also on mature osteoclasts and prostate cancer cells, imaging of osseous metastases with αvβ3-targeted tracers seems promising. However, little is known about the patterns of αvβ3-expression in metastasized prostate cancer lesions in-vivo. Thus we evaluated the uptake of the αvβ3-specific PET tracer [18F]...

متن کامل

Comparison of cyclic RGD peptides for αvβ3 integrin detection in a rat model of myocardial infarction

BACKGROUND Expression of αvβ3 integrin is increased after myocardial infarction as part of the repair process. Increased expression of αvβ3 has been shown by molecular imaging with 18F-galacto-RGD in a rat model. The 68Ga-labelled RGD compounds 68Ga-NODAGA-RGD and 68Ga-TRAP(RGD)3 have high specificity and affinity, and may therefore serve as alternatives of 18F-galacto-RGD for integrin imaging....

متن کامل

Noninvasive Visualization of the Activated αvβ3 Integrin in Cancer Patients by Positron Emission Tomography and [18F]Galacto-RGD

BACKGROUND The integrin alphavbeta3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being studied to enable noninvasive determination of alphavbeta3 expression. We developed [(18)F]Galacto-RGD, a (18)F-labeled glycosylated alphavbeta3 antagonist, allowing monitoring of alphavbe...

متن کامل

PET Radiopharmaceuticals for Imaging Integrin Expression: Tracers in Clinical Studies and Recent Developments

Noninvasive determination of integrin expression has become an interesting approach in nuclear medicine. Since the discovery of the first 18F-labeled cyclic RGD peptide as radiotracer for imaging integrin αvβ3 expression in vivo, there have been carried out enormous efforts to develop RGD peptides for PET imaging. Moreover, in recent years, additional integrins, including α5β1 and αvβ6 came int...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of nuclear medicine : official publication, Society of Nuclear Medicine

دوره 46 1  شماره 

صفحات  -

تاریخ انتشار 2005