First in-human radiation dosimetry of ^sup 68^Ga-NODAGA-RGDyK

• Published in: EJNMMI research 2017-05, Vol.7 (1), p.1
• Main Authors: Gnesin, Silvano, Mitsakis, Periklis, Cicone, Francesco, Deshayes, Emmanuel, Dunet, Vincent, Gallino, Augusto F, Kosinski, Marek, Baechler, Sébastien, Buchegger, Franz, Viertl, David, Prior, John O
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Bladder; Brain; Colon; Computed tomography; Dosimeters; Dosimetry; Extrapolation; Heart diseases; Kidneys; Liver; Lungs; Organs; Pancreas; Patients; Positron emission; Spleen; Stomach; Tomography
• ISSN: 2191-219X
• DOI: 10.1186/s13550-017-0288-x

Integrin-targeting radiopharmaceuticals have potential broad applications, spanning from cancer theranostics to cardiovascular diseases. We have previously reported preclinical dosimetry results of 68Ga-NODAGA-RGDyK in mice. This study presents the first human dosimetry of 68Ga-NODAGA-RGDyK in the five consecutive patients included in a clinical imaging protocol of carotid atherosclerotic plaques. Five male patients underwent whole-body time-of-flight (TOF) PET/CT scans 10, 60 and 120 min after tracer injection (200 MBq). Quantification of 68Ga activity concentration was first validated by a phantom study. To be used as input in OLINDA/EXM, time-activity curves were derived from manually drawn regions of interest over the following organs: brain, thyroid, lungs, heart, liver, spleen, stomach, kidneys, red marrow, pancreas, small intestine, colon, urinary bladder and whole body. A separate dosimetric analysis was performed for the choroid plexuses. Female dosimetry was extrapolated from male data. Effective doses (EDs) were estimated according to both ICRP60 and ICRP103 assuming 30-min and 1-h voiding cycles. The body regions receiving the highest dose were urinary bladder, kidneys and choroid plexuses. For a 30-min voiding cycle, the EDs were 15.7 and 16.5 μSv/MBq according to ICRP60 and ICRP103, respectively. The extrapolation to female dosimetry resulted in organ absorbed doses 17% higher than those of male patients, on average. The 1-h voiding cycle extrapolation resulted in EDs of 19.3 and 19.8 μSv/MBq according to ICRP60 and ICRP103, respectively. A comparison is made with previous mouse dosimetry and with other human studies employing different RGD-based radiopharmaceuticals. According to ICRP60/ICRP103 recommendations, an injection of 200 MBq 68Ga-NODAGA-RGDyK leads to an ED in man of 3.86/3.92 mSv. For future therapeutic applications, specific attention should be directed to delivered dose to kidneys and potentially also to the choroid plexuses. Clinical trial.gov, NCT01608516