Radiotracer in Kombination mit Magnetresonanz-Kontrastmittel für die simultane MR-PET-Bildgebung

Zusammenfassung

Moderne bildgebende Verfahren der medizinischen Diagnostik, wie die Magnetresonanz-Tomographie (MRT) und die Positronen-Emissions-Tomografie (PET), erlauben eine immer präzisere und differenziertere Untersuchung von Krankheiten. Neben dem reinen PET- bzw. MRT-Ansatz befassen sich neue Methoden mit der simultanen PET-MR-Bildgebung, die erst durch die Entwicklung hybrider PET-MRT-Scanner ermöglicht wurde. Diese komplementären Bildgebungsverfahren kombinieren dabei in synergistischer Weise die hohe Auflösung durch MRT mit der großen Sensitivität durch die PET-Methode. Eine Möglichkeit, die Synergie beider Techniken zu nutzen, besteht darin, bereits klinisch etablierte PET-Radiopharmaka mit zugelassenen, paramagnetischen MR-Kontrastmitteln zu kombinieren. Diese Methode wurde in zahlreichen präklinischen und klinischen Studien untersucht. Eine alternative und elegantere Möglichkeit ist die Einführung beider Modalitäten in einer einzigen Kontrastsonde für die nicht invasive bimodale Bildgebung. Hier sind verschiedene Ansätze entwickelt worden, die jedoch umfangreichere Entwicklungsarbeit erfordern. Diese multifunktionellen Kontrastsonden wurden daher bislang nur in präklinischen Studien eingesetzt.

Abstract

Modern imaging techniques in medical diagnostics, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), allow increasingly precise and differential examination of diseases. In addition to the pure PET or MRI approach, new methods deal with simultaneous PET-MR imaging, which was first made possible by the development of hybrid PET-MRI scanners. These complementary imaging modalities synergistically combine the high resolution of MRI with the high sensitivity of PET. One way to exploit the synergy of both techniques is to combine already clinically established PET radiopharmaceuticals with approved paramagnetic MRI contrast agents. This method has been investigated in numerous preclinical and clinical studies. An alternative and more elegant option is to introduce both modalities in a single contrast probe for bimodal imaging. Various approaches have been developed here, but these require more extensive development work. These multifunctional contrast probes for non-invasive bimodal imaging have therefore only been used in preclinical studies to date.

Schlüsselwörter

Positronen-Emission-Tomographie - Magnetresonanztomographie - simultane MR-PET-Bildgebung - Radiotracer, MRT-Kontrastmittel

Keywords

Positron emission tomography - Magnetic resonance tomography - simultaneous MR-PET imaging - radiotracer - magnetic resonance imaging contrast agent

Publication History

Article published online:
10 June 2021

• Literatur

• 1 Judenhofer MS, Wehrl HF, Newport DF. et al. Simultaneous PET-MRI: a new approach for functional and morphological imaging. Nature Medicine 2008; 14: 459-465
• 2 Cabello J, Ziegler SI. Advances in PET/MR instrumentation and image reconstruction. Br J Radiol 2018;
• 3 Izquierdo-Garcia D, Catana C. MR Imaging–Guided Attenuation Correction of PET Data in PET/MR Imaging. PET Clinics 2016; 11: 129-149
• 4 Merbach A, Helm L, Tóth E. The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging. Chichester, England: John Wiley & Sons Ltd; 2013
• 5 Shuvaev S, Akam E, Caravan P. Molecular MR Contrast Agents. Investigative Radiology 2021; 56: 20-34
• 6 Iwaki S, Hokamura K, Ogawa M. et al. A design strategy for small molecule-based targeted MRI contrast agents: their application for detection of atherosclerotic plaques. Org Biomol Chem 2014; 12: 8611-8618
• 7 Yang CT, Chuang KH. Gd(III) chelates for MRI contrast agents: From high relaxivity to "smart", from blood pool to blood-brain barrier permeable. MedChemComm 2012; 3: 552-565
• 8 Gadoliniumhaltige Kontrastmittel: Gadoliniumablagerungen im Gehirn und anderen Geweben. BfArM; 2020 Verfügbar unter: https://www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakovigilanz/DE/RV_STP/g-l/gadolinium-kernspin-neu.html
• 9 Drahoš B, Lukeš I, Tóth É. Manganese(II) Complexes as Potential Contrast Agents for MRI. Eur J Inorg Chem 2012; 2012: 1975-1986
• 10 de Rosales RTM. Potential clinical applications of bimodal PET-MRI or SPECT-MRI agents. J Labelled Compd Radiopharm 2014; 57: 298-303
• 11 Louie A. Multimodality Imaging Probes: Design and Challenges. Chem Rev 2010; 110: 3146-3195
• 12 Yang C-T, Ghosh KK, Padmanabhan P. et al. PET-MR and SPECT-MR multimodality probes: Development and challenges. Theranostics 2018; 8: 6210-6232
• 13 Sandiford L, de Rosales RTM. The Use of Contrast Agents in Clinical and Preclinical PET-MR Imaging. PET clinics 2016; 11: 119-128
• 14 Miller-Thomas MM, Benzinger TL. Neurologic Applications of PET/MR Imaging. Magn Reson Imaging Clin N Am 2017; 25: 297-313
• 15 Donner D, Rozzanigo U, Amelio D. et al. PET in brain tumors. Clin Transl Imaging 2019; 7: 45-60
• 16 Bailey DL, Antoch G, Bartenstein P. et al. Combined PET/MR: The Real Work Has Just Started. Summary Report of the Third International Workshop on PET/MR Imaging; February 17-21, 2014, Tübingen, Germany. Mol Imaging Biol 2015; 17: 297-312
• 17 Fraum TJ, Fowler KJ, McConathy J. PET/MRI:: Emerging Clinical Applications in Oncology. Academic Radiology 2016; 23: 220-236
• 18 Buchbender C, Heusner TA, Lauenstein TC. et al. Oncologic PET/MRI, Part 2: Bone Tumors, Soft-Tissue Tumors, Melanoma, and Lymphoma. J Nucl Med 2012; 53: 1244-1252
• 19 Bailey JJ, Jordan EJ, Burke C. et al. Does Extended PET Acquisition in PET/MRI Rectal Cancer Staging Improve Results?. American Journal of Roentgenology 2018; 211: 896-900
• 20 Filss CP, Cicone F, Shah NJ. et al. Amino acid PET and MR perfusion imaging in brain tumours. Clin Transl Imaging 2017; 5: 209-223
• 21 Afshar-Oromieh A, Haberkorn U, Schlemmer HP. et al. Comparison of PET/CT and PET/MRI hybrid systems using a 68Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience. Eur J Nucl Med Mol Imaging 2014; 41: 887-897
• 22 Makowski MR, Rischpler C, Ebersberger U. et al. Multiparametric PET and MRI of myocardial damage after myocardial infarction: correlation of integrin αvβ3 expression and myocardial blood flow. Eur J Nucl Med Mol Imaging 2020;
• 23 Zhou J, Heo H-Y, Knutsson L. et al. APT-weighted MRI: Techniques, current neuro applications, and challenging issues. Journal of Magnetic Resonance Imaging 2019; 50: 347-364
• 24 Sun H, Xin J, Zhou J. et al. Applying Amide Proton Transfer MR Imaging to Hybrid Brain PET/MR: Concordance with Gadolinium Enhancement and Added Value to [18F]FDG PET. Mol Imaging Biol 2018; 20: 473-481
• 25 Li B, Sun H, Zhang S. et al. Amide proton transfer imaging to evaluate the grading of squamous cell carcinoma of the cervix: A comparative study using 18F FDG PET. Journal of Magnetic Resonance Imaging 2019; 50: 261-268
• 26 Nelson SJ, Kurhanewicz J, Vigneron DB. et al. Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate. Sci Transl Med 2013; 5: 198ra108
• 27 Notni J, Hermann P, Dregely I. et al. Convenient Synthesis of Ga-68-Labeled Gadolinium(III) Complexes: Towards Bimodal Responsive Probes for Functional Imaging with PET/MRI. Chem - Eur J 2013; 19: 12602-12606
• 28 Ermert J, Neumaier B. CHAPTER 20: Radiotracers for PET and MR-PET Imaging. New Developments in NMR 2019; 381-399
• 29 Coenen HH, Ermert J. Expanding PET-applications in life sciences with positron-emitters beyond fluorine-18. Nucl Med Biol 2021; 92: 241-269
• 30 Qaim SM. Nuclear data for production and medical application of radionuclides: Present status and future needs. Nucl Med Biol 2017; 44: 31-49
• 31 Lamb J, Holland JP. Advanced Methods for Radiolabeling Multimodality Nanomedicines for SPECT/MRI and PET/MRI. J Nucl Med 2018; 59: 382-389
• 32 Lahooti A, Sarkar S, Laurent S. et al. Dual nano-sized contrast agents in PET/MRI: a systematic review. Contrast Media Mol Imaging 2016; 11: 428-447
• 33 Kunjachan S, Ehling J, Storm G. et al. Noninvasive Imaging of Nanomedicines and Nanotheranostics: Principles, Progress, and Prospects. Chem Rev 2015; 115: 10907-10937
• 34 Biederer S. Superparamagnetische Eisenoxid-Nanopartikel. In Magnet-Partikel-Spektrometer Medizintechnik (Medizinische Bildgebung, Bildverarbeitung und bildgeführte Interventionen). Wiesbaden: Vieweg+Teubner Verlag; 2012.
• 35 Wang Y-XJ, Xuan S, Port M. et al. Recent Advances in Superparamagnetic Iron Oxide Nanoparticles for Cellular Imaging and Targeted Therapy Research. Curr Pharm Des 2013; 19: 6575-6593
• 36 Lee J-H, Huh Y-M, Jun Y-w. et al. Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nature Medicine 2007; 13: 95-99
• 37 Qaim SM, Scholten B, Spahn I. et al. Positron-emitting radionuclides for applications, with special emphasis on their production methodologies for medical use. Radiochim Acta 2019; 107: 1011-1026
• 38 Lee H-Y, Li Z, Chen K. et al. PET/MRI Dual-Modality Tumor Imaging Using Arginine-Glycine-Aspartic (RGD)–Conjugated Radiolabeled Iron Oxide Nanoparticles. J Nucl Med 2008; 49: 1371-1379
• 39 Choi Js, Park JC, Nah H. et al. A Hybrid Nanoparticle Probe for Dual-Modality Positron Emission Tomography and Magnetic Resonance Imaging. Ang Chem Int Ed 2008; 47: 6259-6262
• 40 Thorek DLJ, Ulmert D, Diop NFM. et al. Non-invasive mapping of deep-tissue lymph nodes in live animals using a multimodal PET/MRI nanoparticle. Nat Commun 2014; 5: 3097
• 41 Chen F, Ellison PA, Lewis CM. et al. Chelator-Free Synthesis of a Dual-Modality PET/MRI Agent. Ang Chem Int Ed 2013; 52: 13319-13323
• 42 Boros E, Bowen AM, Josephson L. et al. Chelate-free metal ion binding and heat-induced radiolabeling of iron oxide nanoparticles. Chem Sci 2015; 6: 225-236
• 43 Chakravarty R, Valdovinos HF, Chen F. et al. Intrinsically Germanium-69-Labeled Iron Oxide Nanoparticles: Synthesis and In-Vivo Dual-Modality PET/MR Imaging. Adv Mater 2014; 26: 5119-5123
• 44 Pellico J, Ruiz-Cabello J, Saiz-Alia M. et al. Fast synthesis and bioconjugation of 68Ga core-doped extremely small iron oxide nanoparticles for PET/MR imaging. Contrast Media Mol Imaging 2016; 11: 203-210
• 45 Abou DS, Thorek DLJ, Ramos NN. et al. 89Zr-Labeled Paramagnetic Octreotide-Liposomes for PET-MR Imaging of Cancer. Pharm Res 2013; 30: 878-888
• 46 Mier W, Babich J, Haberkorn U. Is nano too big?. Eur J Nucl Med Mol Imaging 2014; 41: 4-6
• 47 Kiessling F, Mertens ME, Grimm J. et al. Nanoparticles for imaging: Top or flop?. Radiology 2014; 273: 10-28
• 48 Grimm J, Scheinberg DA. Will Nanotechnology Influence Targeted Cancer Therapy?. Seminars in Radiation Oncology 2011; 21: 80-87
• 49 Overoye-Chan K, Koerner S, Looby RJ. et al. EP-2104R: A Fibrin-Specific Gadolinium-Based MRI Contrast Agent for Detection of Thrombus. J Am Chem Soc 2008; 130: 6025-6039
• 50 Uppal R, Catana C, Ay I. et al. Bimodal Thrombus Imaging: Simultaneous PET/MR Imaging with a Fibrin-targeted Dual PET/MR Probe-Feasibility Study in Rat Model. Radiology 2011; 258: 812-820
• 51 Frullano L, Catana C, Benner T. et al. Bimodal MR–PET Agent for Quantitative pH Imaging. Angew Chem, Int Ed 2010; 49: 2382-2384
• 52 Vanasschen C, Brandt M, Ermert J. et al. Authentically radiolabelled Mn(II) complexes as bimodal PET/MR tracers. EJNMMI physics 2015; 2: A85
• 53 Denzler FO, Lebedev NA, Novgorodov AF. et al. Production and radiochemical separation of 147Gd. Appl Rad Isot 1997; 48: 319-326
• 54 Coenen HH, Buchholz M, Spahn I. et al. Towards authentically labelled bi-modal PET(SPECT)/MR-probes. EJNMMI Physics 2014; 1: A79
• 55 Vanasschen C, Brandt M, Ermert J. et al. Radiolabelling with isotopic mixtures of 52g/55Mn(II) as a straight route to stable manganese complexes for bimodal PET/MR imaging. Dalton Trans 2016; 45: 1315-1321
• 56 Mastarone DJ, Harrison VSR, Eckermann AL. et al. A Modular System for the Synthesis of Multiplexed Magnetic Resonance Probes. J Am Chem Soc 2011; 133: 5329-5337
• 57 Vanasschen C, Molnár E, Tircsó G. et al. Novel CDTA-based, Bifunctional Chelators for Stable and Inert MnII Complexation: Synthesis and Physicochemical Characterization. Inorg Chem 2017; 56: 7746-7760
• 58 Brandt MR, Vanasschen C, Ermert J. et al. 52g/55Mn-Labelled CDTA-based trimeric complexes as novel bimodal PET/MR probes with high relaxivity. Dalton Trans 2019; 48: 3003-3008
• 59 Wagner CC, Langer O. Approaches using molecular imaging technology - use of PET in clinical microdose studies. Adv Drug Delivery Rev 2011; 63: 539-546