First in-human radiation dosimetry of (68)Ga-NODAGA-RGDyK.

Integrin-targeting radiopharmaceuticals have potential broad applications, spanning from cancer theranostics to cardiovascular diseases. We have previously reported preclinical dosimetry results of (68)Ga-NODAGA-RGDyK in mice. This study presents the first human dosimetry of (68)Ga-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 (68)Ga 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 (68)Ga-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

NanoSIMS isotopic analysis of small presolar grains : search for Si3N4 grains from AGB stars and Al and Ti isotopic compositions of rare presolar SiC grains

We report isotopic ratio measurements of small SiC and Si3N4grains, with special emphasis on presolar SiC grains of type Z, and new nucleosynthesis models for 26Al/27Al and the Ti isotopic ratios in asymptotic giant branch (AGB) stars. With the NanoSIMS we analyzed 310 SiC grains from Murchison (carbonaceous CM2 chondrite) separate KJB (diameters 0.25-0.45 μm) and 153 SiC grains from KJG (diameters 1.8-3.7 μm), 154 SiC and 23 Si3N4 grains from Indarch (enstatite EH4 chondrite) separate IH6 (diameters 0.25-0.65 μm) for their C and N isotopic compositions, 549 SiC and 142 Si3N4 grains from IH6 for their C and Si isotopic compositions, 13 SiC grains from Murchison and 66 from Indarch for their Al-Mg compositions, and eight SiC grains from Murchison and 10 from Indarch for their Ti isotopic compositions. One of the original objectives of this effort was to compare isotopic analyses with the NanoSIMS with analyses previously obtained with the Cameca IMS 3f ion microprobe. Many of the Si3N4 grains from Indarch have isotopic anomalies but most of these apparently originate from adjacent SiC grains. Only one Si3N4 grain, with 13C and 14N excesses, has a likely AGB origin. The C, N, and Si isotopic data show that the percentage of SiC grains of type Y and Z increase with decreasing grain size (from ∼1% for grains >2 μm to ∼5-7% for grains of 0.5 μm), providing an opportunity for isotopic analyses in these rare grains. Our measurements expand the number of Al-Mg analyses on SiC Z grains from 4 to 23 and the number of Ti analyses on Z grains from 2 to 11. Inferred26Al/27Al ratios of Z grains are in the range found in mainstream and Y grains and do not exceed those predicted by models of AGB nucleosynthesis. Cool bottom processing (CBP) has been invoked to explain the low 12C/13C ratios of Z grains, but this process apparently does not lead to increased 26Al production in the parent stars of these grains. This finding is in contrast to presolar oxide grains where CBP is needed to explain their high 26Al/27Al ratios. The low 46,47,49 Tι/48Τi ratios found in Z grains and their correlation with low 29Si/28Si ratios extend the trend seen in mainstream grains and confirm an origin in low-metallicity AGB stars. The relatively large excesses in 30Si and 50Ti in Z grains are predicted by our models to be the result of increased production of these isotopes by neutron-capture nucleosynthesis in low-metallicity AGB stars. However, the predicted excesses in 50Ti (and 49Ti) are much larger than those found. Even lowering the strength of the 13C pocket cannot solve this discrepancy in a consistent way