Preclinical Evaluation of Radiolabeled Peptides for PET Imaging of Glioblastoma Multiforme

In this study, we have compared four 68Ga-labeled peptides (three Arg-Gly-Asp (RGD) peptides and substance-P) with two 18F-tracers clinically approved for tumor imaging. We have studied in vitro and in vivo characteristics of selected radiolabeled tracers in a glioblastoma multiforme tumor model. The in vitro part of the study was mainly focused on the evaluation of radiotracers stability under various conditions. We have also determined in vivo stability of studied 68Ga-radiotracers by analysis of murine urine collected at various time points after injection. The in vivo behavior of tested 68Ga-peptides was evaluated through ex vivo biodistribution studies and PET/CT imaging. The obtained data were compared with clinically used 18F-tracers. 68Ga-RGD peptides showed better imaging properties compared to 18F-tracers, i.e., higher tumor/background ratios and no accumulation in non-target organs except for excretory organs.

[1]  E. Hibler,et al.  The Coincidence Between Increasing Age, Immunosuppression, and the Incidence of Patients With Glioblastoma , 2019, Front. Pharmacol..

[2]  Jinming Yu,et al.  Diagnostic and Predictive Value of Using RGD PET/CT in Patients with Cancer: A Systematic Review and Meta-Analysis , 2019, BioMed research international.

[3]  G. Fink,et al.  FET PET reveals considerable spatial differences in tumour burden compared to conventional MRI in newly diagnosed glioblastoma , 2018, Nuklearmedizin.

[4]  Xudong Shi,et al.  Integrin αvβ3 receptor targeting PET/MRI dual-modal imaging probe based on the 64Cu labeled manganese ferrite nanoparticles. , 2018, Journal of inorganic biochemistry.

[5]  P. Delgado-López,et al.  Treatment-related changes in glioblastoma: a review on the controversies in response assessment criteria and the concepts of true progression, pseudoprogression, pseudoresponse and radionecrosis , 2018, Clinical and Translational Oncology.

[6]  E. D. de Vries,et al.  Serial FLT PET imaging to discriminate between true progression and pseudoprogression in patients with newly diagnosed glioblastoma: a long-term follow-up study , 2018, European Journal of Nuclear Medicine and Molecular Imaging.

[7]  G. Karcher,et al.  PET imaging of 68Ga-NODAGA-RGD, as compared with 18F-fluorodeoxyglucose, in experimental rodent models of engrafted glioblastoma , 2018, EJNMMI Research.

[8]  J. Talbot,et al.  [68Ga]RGD Versus [18F]FDG PET Imaging in Monitoring Treatment Response of a Mouse Model of Human Glioblastoma Tumor with Bevacizumab and/or Temozolomide , 2018, Molecular Imaging and Biology.

[9]  Huijie Jiang,et al.  Prediction of tumor biological characteristics in different colorectal cancer liver metastasis animal models using 18F-FDG and 18F-FLT. , 2018, Hepatobiliary & pancreatic diseases international : HBPD INT.

[10]  I. Marriott,et al.  Human microglia and astrocytes constitutively express the neurokinin-1 receptor and functionally respond to substance P , 2017, Journal of Neuroinflammation.

[11]  A. Mahajan,et al.  Sex as a Biologic Variable in Preclinical Imaging Research: Initial Observations with 18F-FLT , 2017, The Journal of Nuclear Medicine.

[12]  M. Schwaiger,et al.  Exploring the Role of RGD-Recognizing Integrins in Cancer , 2017, Cancers.

[13]  John O. Prior,et al.  68Ga-NODAGA-RGDyK PET/CT Imaging in Esophageal Cancer: First-in-Human Imaging. , 2016, Clinical nuclear medicine.

[14]  J. Jeong,et al.  Angiogenesis Imaging Using (68)Ga-RGD PET/CT: Therapeutic Implications. , 2016, Seminars in nuclear medicine.

[15]  G. Fròsina.  Non-routine Tracers for PET Imaging of High-grade Glioma. , 2016, Anticancer research.

[16]  C. Decristoforo,et al.  Comparison of Ga-68-Labeled Fusarinine C-Based Multivalent RGD Conjugates and [68Ga]NODAGA-RGD—In Vivo Imaging Studies in Human Xenograft Tumors , 2016, Molecular Imaging and Biology.

[17]  G. Fròsina.  Positron emission tomography of high-grade gliomas , 2016, Journal of Neuro-Oncology.

[18]  M. Redondo,et al.  The substance P/NK-1 receptor system: NK-1 receptor antagonists as anti-cancer drugs , 2015, Journal of Biosciences.

[19]  Xiaoyuan Chen,et al.  68Ga-PRGD2 PET/CT in the Evaluation of Glioma: A Prospective Study , 2014, Molecular pharmaceutics.

[20]  J. Knuuti,et al.  Pharmacological Activation of the Melanocortin System Limits Plaque Inflammation and Ameliorates Vascular Dysfunction in Atherosclerotic Mice , 2014, Arteriosclerosis, thrombosis, and vascular biology.

[21]  Clemens Decristoforo,et al.  Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles , 2013, International journal of nanomedicine.

[22]  Y. Seimbille,et al.  Synthesis and in vitro evaluation of a novel radioligand for αvβ3 integrin receptor imaging: [18F]FPPA-c(RGDfK). , 2013, Bioorganic & medicinal chemistry letters.

[23]  M. Nykter,et al.  Insulin-like growth factor-binding protein 2-driven glioma progression is prevented by blocking a clinically significant integrin, integrin-linked kinase, and NF-κB network , 2012, Proceedings of the National Academy of Sciences.

[24]  M. Huizing,et al.  Retro-orbital injections in mice , 2011, Lab Animal.

[25]  B. Pichler,et al.  [68Ga]NODAGA-RGD for imaging αvβ3 integrin expression , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[26]  Kai Chen,et al.  18F-Labeled Galacto and PEGylated RGD Dimers for PET Imaging of αvβ3 Integrin Expression , 2010, Molecular Imaging and Biology.

[27]  B. Krause,et al.  Characterization of choline uptake in prostate cancer cells following bicalutamide and docetaxel treatment , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[28]  Xiaoyuan Chen,et al.  68Ga-labeled multimeric RGD peptides for microPET imaging of integrin {alpha}v{beta}3 expression , 2008 .

[29]  J. Tonn,et al.  Expression of Integrin αvβ3 in Gliomas Correlates with Tumor Grade and Is not Restricted to Tumor Vasculature , 2008, Brain pathology.

[30]  Xiaoyuan Chen,et al.  68Ga-labeled multimeric RGD peptides for microPET imaging of integrin αvβ3 expression , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[31]  Wei Chen.  Clinical Applications of PET in Brain Tumors* , 2007, Journal of Nuclear Medicine.

[32]  Horst Kessler,et al.  Noninvasive Visualization of the Activated αvβ3 Integrin in Cancer Patients by Positron Emission Tomography and [18F]Galacto-RGD , 2005, PLoS medicine.

[33]  Ryan Park,et al.  MicroPET imaging of breast cancer alphav-integrin expression with 64Cu-labeled dimeric RGD peptides. , 2004, Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.

[34]  F. Kobarfard,et al.  Synthesis and Preliminary Evaluation of a New 99mTc Labeled Substance P Analogue as a Potential Tumor Imaging Agent , 2015, Iranian journal of pharmaceutical research : IJPR.

[35]  M. Schwaiger,et al.  [18F]Galacto-RGD: synthesis, radiolabeling, metabolic stability, and radiation dose estimates. , 2004, Bioconjugate chemistry.

[36]  Matthew J. Oborski,et al.  Cancer Management and Research Dovepress Malignant Gliomas: Current Perspectives in Diagnosis, Treatment, and Early Response Assessment Using Advanced Quantitative Imaging Methods , 2022 .