Abstract
BackgroundIntegrin-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.ResultsThe 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.ConclusionsAccording 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.Trial registrationClinical trial.gov, NCT01608516
Highlights
Integrin-targeting radiopharmaceuticals have potential broad applications, spanning from cancer theranostics to cardiovascular diseases
A preliminary comparison between 68GaNODAGA-RGDyK and FDG positron emitting (PET)/CT suggests a higher rate of lesion detection for 68Ga-NODAGA-RGDyK, with 3/5 sites of carotid stenosis showing increased uptake values compared with the controlateral side
For a 30-min voiding cycle, the Effective doses (EDs) were 15.7 and 16.5 μSv/MBq according to ICRP60 and ICRP103, respectively
Summary
Integrin-targeting radiopharmaceuticals have potential broad applications, spanning from cancer theranostics to cardiovascular diseases. 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). A specific marker of angiogenesis is the avβ integrin, which is targeted with high affinity by the peptidic compound arginine-glycine-aspartic acid (RGD). Several proteins of the extracellular matrix like vitronectin, fibrinogen and fibronectin interact with integrin ανβ via the RGD sequence [2]. A number of single photon (SPECT) and positron emitting (PET) tracers for ανβ integrin have been developed based on RGD cyclic sequences, such as RGDyK or Gnesin et al EJNMMI Research (2017) 7:43. Radiolabelling of generator-produced 68Ga with either DOTA or NODAGA chelators allows for a more efficient, faster and fully automated production [5,6,7,8,9]
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