Thomas Ebenhan1,2, Janke Kleynhans3,4, Jan Rijn Zeevaart4,5, Jae Min Jeong6, Mike Sathekge3. 1. Nuclear Medicine, University of Pretoria, Pretoria, 0001, South Africa. thomas.ebenhan@up.ac.za. 2. Nuclear Medicine Research Infrastructure, NPC, Pretoria, 0001, South Africa. thomas.ebenhan@up.ac.za. 3. Nuclear Medicine, University of Pretoria, Pretoria, 0001, South Africa. 4. Nuclear Medicine Research Infrastructure, NPC, Pretoria, 0001, South Africa. 5. DST/NWU Preclinical Drug Development Platform, North-West University, Potchefstroom, 2520, South Africa. 6. Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, 101 Daehangno Jongno-gu, Seoul, 110-744, South Korea.
Abstract
INTRODUCTION: Non-invasive imaging techniques (especially single-photon emission tomography and positron emission tomography) apply several RGD-based imaging ligands developed during a vast number of preclinical and clinical investigations. The RGD (Arg-Gly-Asp) sequence is a binding moiety for a large selection of adhesive extracellular matrix and cell surface proteins. Since the first identification of this sequence as the shortest sequence required for recognition in fibronectin during the 1980s, fundamental research regarding the molecular mechanisms of integrin action have paved the way for development of several pharmaceuticals and radiopharmaceuticals with clinical applications. Ligands recognizing RGD may be developed for use in the monitoring of these interactions (benign or pathological). Although RGD-based molecular imaging has been actively investigated for oncological purposes, their utilization towards non-oncology applications remains relatively under-exploited. METHODS AND SCOPE: This review highlights the new non-oncologic applications of RGD-based tracers (with the focus on single-photon emission tomography and positron emission tomography). The focus is on the last 10 years of scientific literature (2009-2020). It is proposed that these imaging agents will be used for off-label indications that may provide options for disease monitoring where there are no approved tracers available, for instance Crohn's disease or osteoporosis. Fundamental science investigations have made progress in elucidating the involvement of integrin in various diseases not pertaining to oncology. Furthermore, RGD-based radiopharmaceuticals have been evaluated extensively for safety during clinical evaluations of various natures. CONCLUSION: Clinical translation of non-oncological applications for RGD-based radiopharmaceuticals and other imaging tracers without going through time-consuming extensive development is therefore highly plausible. Graphical abstract.
INTRODUCTION: Non-invasive imaging techniques (especially single-photon emission tomography and positron emission tomography) apply several RGD-based imaging ligands developed during a vast number of preclinical and clinical investigations. The RGD (Arg-Gly-Asp) sequence is a binding moiety for a large selection of adhesive extracellular matrix and cell surface proteins. Since the first identification of this sequence as the shortest sequence required for recognition in fibronectin during the 1980s, fundamental research regarding the molecular mechanisms of integrin action have paved the way for development of several pharmaceuticals and radiopharmaceuticals with clinical applications. Ligands recognizing RGD may be developed for use in the monitoring of these interactions (benign or pathological). Although RGD-based molecular imaging has been actively investigated for oncological purposes, their utilization towards non-oncology applications remains relatively under-exploited. METHODS AND SCOPE: This review highlights the new non-oncologic applications of RGD-based tracers (with the focus on single-photon emission tomography and positron emission tomography). The focus is on the last 10 years of scientific literature (2009-2020). It is proposed that these imaging agents will be used for off-label indications that may provide options for disease monitoring where there are no approved tracers available, for instance Crohn's disease or osteoporosis. Fundamental science investigations have made progress in elucidating the involvement of integrin in various diseases not pertaining to oncology. Furthermore, RGD-based radiopharmaceuticals have been evaluated extensively for safety during clinical evaluations of various natures. CONCLUSION: Clinical translation of non-oncological applications for RGD-based radiopharmaceuticals and other imaging tracers without going through time-consuming extensive development is therefore highly plausible. Graphical abstract.
Authors: Ji-Ae Park; Jung Young Kim; Yong Jin Lee; Wonho Lee; Sang Moo Lim; Tae-Jeong Kim; Jeongsoo Yoo; Yongmin Chang; Kyeong Min Kim Journal: ACS Med Chem Lett Date: 2012-12-17 Impact factor: 4.345
Authors: Kornelis S M van der Geest; Maria Sandovici; Pieter H Nienhuis; Riemer H J A Slart; Peter Heeringa; Elisabeth Brouwer; William F Jiemy Journal: Front Med (Lausanne) Date: 2022-06-06
Authors: Matthieu Dietz; Christel H Kamani; Vincent Dunet; Stephane Fournier; Vladimir Rubimbura; Nathalie Testart Dardel; Ana Schaefer; Mario Jreige; Sarah Boughdad; Marie Nicod Lalonde; Niklaus Schaefer; Nathan Mewton; John O Prior; Giorgio Treglia Journal: Front Med (Lausanne) Date: 2022-05-06