PDF herunterladen
Exp Clin Endocrinol Diabetes 2014; 122(2): 79-86
DOI: 10.1055/s-0033-1363232
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Molecular Imaging of Pancreatic Islet Transplantation

Y. Liu
1   West China Hospital, Radiology, Chengdu, China
,
B. Song
1   West China Hospital, Radiology, Chengdu, China
,
X. Ran
2   West China Hospital, Endocrinology, Chengdu, China
,
Q. Jiang
3   Henry Ford Health System, Neurology, Detroit, United States
,
J. Hu
4   Wayne State University, Detroit, United States
,
S. M. Vance Chiang
5   West China College of Medicine, Sichuan University, Chengdu, China
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 15. Mai 2013
first decision 24. Oktober 2013

accepted 27. November 2013

Publikationsdatum:
19. Februar 2014 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Islet replacement therapy, pancreatic islet transplantation, is considered as a potential option for curing T1DM. However, the significant loss of implanted islets after islet transplantation prevents it from becoming a mainstream treatment modality. Due to the lack of reliable noninvasive real-time imaging techniques to track the survival of the islets, it is impossible to discover the specific causes for the loss of implanted islets, not to mention taking interventions in the early stage. Current achievements in molecular imaging has provided with several promising techniques, including optical imaging, PET and MRI, for noninvasive visualization, quantification and functional evaluation of transplanted islets in experimental conditions. Optical imaging seems to be the most convenient and cost-efficient modality, but the limited penetration distance hinders its application in large animal and human studies. PET combined with target-specific tracers is characterized by high specificity and sensitivity for detection of islet grafts, but observation time is rather short (i.e., several hours). MRI stands out for its long-term visualization of transplanted islet grafts with the aid of contrast agents. However, quantification of islets remains a problem to be solved. A novel technique, microencapsulation, provides a new perspective in multimodal imaging by optimizing the strengths of several modalities together. Although the application of molecular imaging in clinical settings is still limited, significant success and valuable information is achieved in the basic and clinical trials. However, islet transplantation still remains an experimental procedure, with ongoing researches focusing on islets availability, appropriate sites for implantation, new methods using biomaterials (e.g. microencapsulation), immune modulation and more.

Key words

diabetes mellitus - molecular imaging - pancreatic islet transplantation - contrast agent - islet labeling
 

  • References

  • 1 Whiting DR, Guariguata L, Weil C et al. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011; 94: 311-321
    CrossrefPubMedGoogle Scholar
  • 2 Narayan KV, Boyle JP, Thompson TJ et al. Lifetime risk for diabetes mellitus in the United States. JAMA: the journal of the American Medical Association 2003; 290: 1884-1890
    CrossrefPubMedGoogle Scholar
  • 3 Daneman D. Type 1 diabetes. The Lancet 2006; 367: 847-858
    CrossrefPubMedGoogle Scholar
  • 4 Reichard P, Nilsson B-Y, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. New England Journal of Medicine 1993; 329: 304-309
    CrossrefPubMedGoogle Scholar
  • 5 Group DR. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. J Pediatr 1994; 125: 177-188
    PubMedGoogle Scholar
  • 6 Group DR. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann Intern Med 1998; 128: 517-523
    CrossrefPubMedGoogle Scholar
  • 7 Nathan D, Cleary P, Backlund J et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. The New England journal of medicine 2005; 353: 2643-2653
    CrossrefPubMedGoogle Scholar
  • 8 Shapiro AM, Nanji SA, Lakey JR. Clinical islet transplant: current and future directions towards tolerance. Immunol Rev 2003; 196: 219-236
    CrossrefPubMedGoogle Scholar
  • 9 Shapiro AM, Lakey JR, Ryan EA et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343: 230-238
    CrossrefPubMedGoogle Scholar
  • 10 Ryan EA, Paty BW, Senior PA et al. Five-year follow-up after clinical islet transplantation. Diabetes 2005; 54: 2060-2069
    CrossrefPubMedGoogle Scholar
  • 11 Barshes NR, Wyllie S, Goss JA. Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts. J Leukoc Biol 2005; 77: 587-597
    CrossrefPubMedGoogle Scholar
  • 12 Robertson RP. Pancreas and islet transplants for patients with diabetes: taking positions and making decisions. Endocr Pract 1999; 5: 24-28
    CrossrefPubMedGoogle Scholar
  • 13 Arifin DR, Bulte JW. Imaging of pancreatic islet cells. Diabetes Metab Res Rev 2011; 27: 761-766
    CrossrefPubMedGoogle Scholar
  • 14 Eich T, Eriksson O, Sundin A et al. Positron emission tomography: a real-time tool to quantify early islet engraftment in a preclinical large animal model. Transplantation 2007; 84: 893-898
    CrossrefPubMedGoogle Scholar
  • 15 Weissleder R. Molecular imaging: exploring the next frontier. Radiology 1999; 212: 609-614
    CrossrefPubMedGoogle Scholar
  • 16 Wang P, Medarova Z, Moore A. Molecular imaging: a promising tool to monitor islet transplantation. J Transplant 2011; 2011: 1-14
    PubMedGoogle Scholar
  • 17 Medarova Z, Moore A. Non-invasive detection of transplanted pancreatic islets. Diabetes Obes Metab 2008; 10: 88-97
    CrossrefPubMedGoogle Scholar
  • 18 Medarova Z, Vallabhajosyula P, Tena A et al. In Vivo Imaging of Autologous Islet Grafts in the Liver and Under the Kidney Capsule in Non-Human Primates. Transplantation 2009; 87: 1659-1666
    CrossrefPubMedGoogle Scholar
  • 19 Andralojc K, Srinivas M, Brom M et al. Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis. Diabetologia 2012; 55: 1247-1257
    CrossrefPubMedGoogle Scholar
  • 20 Chen X, Zhang X, Larson CS et al. In vivo bioluminescence imaging of transplanted islets and early detection of graft rejection. Transplantation 2006; 81: 1421-1427
    CrossrefPubMedGoogle Scholar
  • 21 Roth DJ, Jansen ED, Powers AC et al. A novel method of monitoring response to islet transplantation: bioluminescent imaging of an NF-kB transgenic mouse model. Transplantation 2006; 81: 1185-1190
    CrossrefPubMedGoogle Scholar
  • 22 Hara M, Yin D, Dizon RF et al. A mouse model for studying intrahepatic islet transplantation. Transplantation 2004; 78: 615-618
    PubMedGoogle Scholar
  • 23 Medarova Z, Bonner-Weir S, Lipes M et al. Imaging beta-cell death with a near-infrared probe. Diabetes 2005; 54: 1780-1788
    CrossrefPubMedGoogle Scholar
  • 24 Lu Y, Dang H, Middleton B et al. Bioluminescent Monitoring of Islet Graft Survival after Transplantation. Mol Ther 2004; 9: 428-435
    CrossrefPubMedGoogle Scholar
  • 25 Chen X, Zhang X, Larson CS et al. In Vivo Bioluminescence Imaging of Transplanted Islets and Early Detection of Graft Rejection. Transplantation 2006; 81: 1421-1427
    CrossrefPubMedGoogle Scholar
  • 26 Fowler M, Virostko J, Chen Z et al. Assessment of pancreatic islet mass after islet transplantation using in vivo bioluminescence imaging. Transplantation 2005; 79: 768-776
    CrossrefPubMedGoogle Scholar
  • 27 Virostko J, Radhika A, Poffenberger G et al. Bioluminescence imaging in mouse models quantifies β cell mass in the pancreas and after islet transplantation. Mol Imaging Biol 2009; 12: 42-53
    PubMedGoogle Scholar
  • 28 Hara M, Dizon RF, Glick BS et al. Imaging pancreatic beta-cells in the intact pancreas. Am J Physiol Endocrinol Metab 2006; 290: E1041-E1047
    CrossrefPubMedGoogle Scholar
  • 29 Eriksson O, Eich T, Sundin A et al. Positron emission tomography in clinical islet transplantation. Am J Transplant 2009; 9: 2816-2824
    CrossrefPubMedGoogle Scholar
  • 30 Eich T, Eriksson O, Lundgren T. Visualization of early engraftment in clinical islet transplantation by positron-emission tomography. N Engl J Med 2007; 356: 2754-2755
    CrossrefPubMedGoogle Scholar
  • 31 Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 2003; 17: 545-580
    CrossrefPubMedGoogle Scholar
  • 32 Toso C, Zaidi H, Morel P et al. Positron-emission tomography imaging of early events after transplantation of islets of langerhans. Transplantation 2005; 79: 353-355
    CrossrefPubMedGoogle Scholar
  • 33 Adonai N, Nguyen KN, Walsh J et al. Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography. Proc Natl Acad Sci USA 2002; 99: 3030-3035
    CrossrefPubMedGoogle Scholar
  • 34 Lu Y, Dang H, Middleton B et al. Long-term monitoring of transplanted islets using positron emission tomography. Mol Ther 2006; 14: 851-856
    CrossrefPubMedGoogle Scholar
  • 35 Lu Y, Dang H, Middleton B et al. Noninvasive imaging of islet grafts using positron-emission tomography. Proc Natl Acad Sci USA 2006; 103: 11294-11299
    CrossrefPubMedGoogle Scholar
  • 36 Kim S-J, Doudet DJ, Studenov AR et al. Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival. Nat Med 2006; 12: 1423-1428
    PubMedGoogle Scholar
  • 37 Kim HS, Choi Y, Song IC et al. Magnetic resonance imaging and biological properties of pancreatic islets labeled with iron oxide nanoparticles. NMR Biomed 2009; 22: 852-856
    CrossrefPubMedGoogle Scholar
  • 38 Koblas T, Girman P, Berkova Z et al. Magnetic resonance imaging of intrahepatically transplanted islets using paramagnetic beads. Transplant Proc 2005; 37: 3493-3495
    CrossrefPubMedGoogle Scholar
  • 39 Juang JH, Shen CR, Wang JJ et al. Magnetic resonance imaging study of mouse islet allotransplantation. Transplant Proc 2010; 42: 4217-4220
    CrossrefPubMedGoogle Scholar
  • 40 Juang JH, Wang JJ, Shen CR et al. Magnetic resonance imaging of transplanted mouse islets labeled with chitosan-coated superparamagnetic iron oxide nanoparticles. Transplant Proc 2010; 42: 2104-2108
    CrossrefPubMedGoogle Scholar
  • 41 Lee N, Kim H, Choi SH et al. Magnetosome-like ferrimagnetic iron oxide nanocubes for highly sensitive MRI of single cells and transplanted pancreatic islets. Proc Natl Acad Sci USA 2011; 108: 2662-2667
    CrossrefPubMedGoogle Scholar
  • 42 Zhang B, Jiang B, Chen Y et al. Detection of viability of transplanted beta cells labeled with a novel contrast agent – polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles by magnetic resonance imaging. Contrast Media Mol Imaging 2012; 7: 35-44
    CrossrefPubMedGoogle Scholar
  • 43 Jirak D, Kriz J, Herynek V et al. MRI of transplanted pancreatic islets. Magn Reson Med 2004; 52: 1228-1233
    CrossrefPubMedGoogle Scholar
  • 44 Evgenov NV, Medarova Z, Dai G et al. In vivo imaging of islet transplantation. Nat Med 2006; 12: 144-148
    CrossrefPubMedGoogle Scholar
  • 45 Biancone L, Crich SG, Cantaluppi V et al. Magnetic resonance imaging of gadolinium-labeled pancreatic islets for experimental transplantation. NMR Biomed 2007; 20: 40-48
    CrossrefPubMedGoogle Scholar
  • 46 Ricordi C, Strom TB. Clinical islet transplantation: advances and immunological challenges. Nat Rev Immunol 2004; 4: 259-268
    CrossrefPubMedGoogle Scholar
  • 47 Kriz J, Jirak D, White D et al. Magnetic resonance imaging of pancreatic islets transplanted into the right liver lobes of diabetic mice. Transplant Proc 2008; 40: 444-448
    CrossrefPubMedGoogle Scholar
  • 48 Kim HS, Kim H, Park KS et al. Evaluation of porcine pancreatic islets transplanted in the kidney capsules of diabetic mice using a clinically approved superparamagnetic iron oxide (SPIO) and a 1.5T MR scanner. Korean J Radiol 2010; 11: 673-682
    CrossrefPubMedGoogle Scholar
  • 49 Tai JH, Foster P, Rosales A et al. Imaging islets labeled with magnetic nanoparticles at 1.5 Tesla. Diabetes 2006; 55: 2931-2938
    CrossrefPubMedGoogle Scholar
  • 50 Barnett BP, Arepally A, Karmarkar PV et al. Magnetic resonance–guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat Med 2007; 13: 986-991
    CrossrefPubMedGoogle Scholar
  • 51 Kim JH, Jin SM, Oh SH et al. Counting small hypointense spots confounds the quantification of functional islet mass based on islet MRI. Am J Transplant 2012; 12: 1303-1312
    CrossrefPubMedGoogle Scholar
  • 52 Crowe LA, Ris F, Nielles-Vallespin S et al. A novel method for quantitative monitoring of transplanted islets of langerhans by positive contrast magnetic resonance imaging. Am J Transplant 2011; 11: 1158-1168
    CrossrefPubMedGoogle Scholar
  • 53 Barnett BP, Ruiz-Cabello J, Hota P et al. Use of perfluorocarbon nanoparticles for non-invasive multimodal cell tracking of human pancreatic islets. Contrast Media Mol Imaging 2011; 6: 251-259
    PubMedGoogle Scholar
  • 54 Barnett BP, Ruiz-Cabello J, Hota P et al. Fluorocapsules for improved function, immunoprotection, and visualization of cellular therapeutics with MR, US, and CT imaging. Radiology 2011; 258: 182-191
    CrossrefPubMedGoogle Scholar
  • 55 Hathout E, Sowers L, Wang R et al. In vivo magnetic resonance imaging of vascularization in islet transplantation. Transpl Int 2007; 20: 1059-1065
    CrossrefPubMedGoogle Scholar
  • 56 Chan N, Obenaus A, Tan A et al. Monitoring neovascularization of intraportal islet grafts by dynamic contrast enhanced magnetic resonance imaging. Islets 2009; 1: 249-255
    CrossrefPubMedGoogle Scholar
  • 57 Gauden AJ, Phal PM, Drummond KJ. MRI safety; nephrogenic systemic fibrosis and other risks. J Clin Neurosci 2010; 17: 1097-1104
    CrossrefPubMedGoogle Scholar
  • 58 Zou Z, Zhang HL, Roditi GH et al. Nephrogenic systemic fibrosis: review of 370 biopsy-confirmed cases. JACC Cardiovasc Imaging 2011; 4: 1206-1216
    CrossrefPubMedGoogle Scholar
  • 59 Scott LJ. Gadobutrol: a review of its use for contrast-enhanced magnetic resonance imaging in adults and children. Clin Drug Investig 2013; 33: 303-314
    CrossrefPubMedGoogle Scholar
  • 60 Barnett BP, Kraitchman DL, Lauzon C et al. Radiopaque alginate microcapsules for X-ray visualization and immunoprotection of cellular therapeutics. Mol Pharm 2006; 3: 531-538
    CrossrefPubMedGoogle Scholar
  • 61 Arifin DR, Long CM, Gilad AA et al. Trimodal gadolinium-gold microcapsules containing pancreatic islet cells restore normoglycemia in diabetic mice and can be tracked by using US, CT, and positive-contrast MR imaging. Radiology 2011; 260: 790-798
    CrossrefPubMedGoogle Scholar
  • 62 Steele JA, Barron AE, Carmona E et al. Encapsulation of protein microfiber networks supporting pancreatic islets. J Biomed Mater Res A 2012; 100: 3384-3391
    PubMedGoogle Scholar
  • 63 Kim J, Arifin DR, Muja N et al. Multifunctional capsule-in-capsules for immunoprotection and trimodal imaging. Angew Chem Int Ed Engl 2011; 50: 2317-2321
    CrossrefPubMedGoogle Scholar
  • 64 Link TW, Woodrum D, Gilson WD et al. MR-guided portal vein delivery and monitoring of magnetocapsules: assessment of physiologic effects on the liver. J Vasc Interv Radiol 2011; 22: 1335-1340
    CrossrefPubMedGoogle Scholar
  • 65 Toso C, Vallee JP, Morel P et al. Clinical magnetic resonance imaging of pancreatic islet grafts after iron nanoparticle labeling. Am J Transplant 2008; 8: 701-706
    CrossrefPubMedGoogle Scholar
  • 66 Saudek F, Jirak D, Girman P et al. Magnetic resonance imaging of pancreatic islets transplanted into the liver in humans. Transplantation 2010; 90: 1602-1606
    CrossrefPubMedGoogle Scholar