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

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

Radiation dosimetry of 18F-AzaFol: A first in-human use of a folate receptor PET tracer

“…3). Estimated TIAC for the choroid plexuses with 18 F-AzaFol (4.62E− 04 MBq h/MBq) is higher than TIAC previously reported in [20] where a 68 Ga-RGD compound was used (3.08E− 04 MBq h/MBq). Nevertheless, when considering the same organ mass and geometry (with OLINDA sphere model and a mass of 2.76 g) used for the AD calculation, the AD estimate to the choroid plexuses for the 18 F-Aza-Fol (2.47E− 02 μGy/MBq) was lower than the dose estimated of the 68 Ga-RGD compound (3.96E− 02 μGy/MBq).…”

“…For the choroids, we also applied a more realistic AD estimation using the Monte Carlo-derived analytical approach proposed by Amato et al [19] in which the complex geometry of this organ was approximated using a set of simple geometrical structures such as (cylinders and parallelepipeds). The mass of the choroids was estimated to be 2.76 g and 1.81 g for male and female as previously reported in [20].…”

First in-human radiation dosimetry of the gastrin-releasing peptide (GRP) receptor antagonist 68Ga-NODAGA-MJ9

“…As previously described, quantitative accuracy for 68 Ga PET/CT was assessed to be within 6% of the expected value [20].…”

Head and neck tumors angiogenesis imaging with 68Ga-NODAGA-RGD in comparison to 18F-FDG PET/CT: a pilot study

“…68 Ga-NODAGA-RGD can be produced locally in centers with access to a 68 Ga generator [15] and radiolabeling can be easily done in kit-based or automated modules. It targets the α v β 3 integrins [8][9][10], and showed promising results in animal trials and demonstrated safe dosimetry profile [16][17][18]. Patients with different tumor types have also been reported using 68 Ga-NODAGA-RGD [16,19,20], but no specific study has been performed in a HNSCC population.…”