First in-human radiation dosimetry of the gastrin-releasing peptide (GRP) receptor antagonist Ga-68-NODAGA-MJ9
EJNMMI RESEARCH
Authors: Gnesin, Silvano; Cicone, Francesco; Mitsakis, Periklis; Van der Gucht, Axel; Baechler, Sebastien; Miralbell, Raymond; Garibotto, Valentina; Zilli, Thomas; Prior, John O.
Abstract
BackgroundGastrin-releasing peptide receptor antagonists have promise in theranostics of several highly incident tumours, including prostate and breast. This study presents the first human dosimetry of Ga-68-NODAGA-MJ9 in the first five consecutive patients with recurrent prostate cancer included in a dual-tracer positron emission tomography (PET) protocol. Five male patients with biochemical relapse of prostate adenocarcinoma underwent four whole-body time-of-flight PET/CT scans within 2h after tracer injection. To be used as input in OLINDA/EXM 2.0, time-integrated activity coefficients were derived from manually drawn regions of interest over the following body regions: brain, thyroid, lungs, heart, liver, gallbladder, spleen, stomach, kidneys, adrenals, red marrow, pancreas, intestines, urinary bladder and whole body. Organ absorbed doses and effective dose (ED) were calculated with OLINDA/EXM 2.0 using the NURBS voxelized phantoms adjusted to the ICRP-89 organ masses and ICRP103 tissue-weighting factors. Additional absorbed dose estimations were performed with OLINDA/EXM 1.1 to be comparable with similar previous publications.ResultsThe body regions receiving the highest absorbed doses were the pancreas, the urinary bladder wall, the small intestine and the kidneys (260, 69.8, 38.8 and 34.8Gy/MBq respectively). The ED considering a 30-min urinary voiding cycle was 17.6Sv/MBq in male patients. The increment of voiding time interval produced a significant increase of absorbed doses in bladder, prostate and testes, as well as an increase of ED. ED also increased if calculated with OLINDA/EXM 1.1. These results have been discussed in view of similar publications on bombesin analogues or on other commonly used theranostic peptides.ConclusionsThe pancreas is the most irradiated organ after the injection of Ga-68-NODAGA-MJ9, followed by the urinary bladder wall, the small intestine and the kidneys. ED is in the same range of other common Ga-68-labelled peptides. Differences with similarly published studies on bombesin analogues exist, and are mainly dependent on the methodology used for absorbed dose calculations.Trial registrationClinicaltrial.Gov identifier: NCT02111954, posted on 11/042014.
Long-term follow-up of biomarkers of vascular calcification after switch from traditional hemodialysis to online hemodiafiltration
SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION
Authors: Uhlin, Fredrik; Fernstrom, Anders; Knapen, Marjo H. J.; Vermeer, Cees; Magnusson, Per
Abstract
Rapid progression of vascular calcification (VC) in hemodialysis (HD) patients is caused by several factors including inflammation and an imbalance between active inducers and inhibitors of VC. Growing evidence shows that online hemodiafiltration (ol-HDF), a combination of diffusive and convective solute transport, has positive effects on the uremic environment that affects patients on dialysis. However, we recently reported that serum 25-hydroxyvitamin D (25(OH)D) decreased after a switch from HD to ol-HDF. As a consequence of this finding, the present study was undertaken to investigate if inducers and inhibitors of VC (i.e. the inactive matrix Gla protein fractions dp-ucMGP and t-ucMGP, fetuin-A, Gla-rich protein (GRP), osteopontin (OPN), bone-specific alkaline phosphatase (BALP), and osteoprotegerin (OPG)) also are affected by ol-HDF. This non-comparative prospective study comprised 35 prevalent patients who were investigated 6, 12, and 24 months after their switch from HD to ol-HDF. Most patients had increased levels of the calcification inhibitors OPN and OPG; and of the inactive calcification inhibitor dp-ucMGP during the study period irrespective of the dialysis modality. BALP and t-ucMGP were mostly within the reference interval, but fetuin-A was mostly below the reference interval during the study period. OPN was significantly associated with BALP and parathyroid hormone, r = 0.62 and r = 0.65 (p < .001), respectively. In conclusion, in contrast to decreased 25(OH)D levels, no differences were found for any of the measured biomarkers of VC following the switch from HD to ol-HDF. Further studies are needed to elucidate how these biomarkers can contribute to calcification risk assessment.