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 68Ga-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 2 h 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 34.8 μGy/MBq respectively). The ED considering a 30-min urinary voiding cycle was 17.6 μSv/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 68Ga-NODAGA-MJ9, followed by the urinary bladder wall, the small intestine and the kidneys. ED is in the same range of other common 68Ga-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.
Highlights
Gastrin-releasing peptide receptor antagonists have promise in theranostics of several highly incident tumours, including prostate and breast
The aim of the present study was to assess the human dosimetry of the GRPR antagonist 68Ga-NODAGA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-G ly-His-Sta-Leu-NH2 (NODAGA-MJ9) [16] in the first five patients with recurrent prostate cancer included in a dual-tracer positron emission tomography (PET) protocol
Patients Five prostate cancer patients with biochemical relapse after radical prostatectomy with or without postoperative radiotherapy were enrolled between April and May 2014
Summary
Gastrin-releasing peptide receptor antagonists have promise in theranostics of several highly incident tumours, including prostate and breast. The amphibian skin is a quasi-unlimited source of biologically active peptides, which have been the object of extensive pharmacological studies in the past decades [1]. The mitotic activity of GRP in human tumours is largely mediated by the G-protein-coupled receptor BB2, known as GRP-receptor (GRPR); interestingly, the interference with GRPR-mediated functions produces significant anti-mitotic effects [5, 8]. It follows that the application of GRPR-targeting, radiolabelled bombesin analogues to the imaging and treatment of various neoplasms has raised considerable interest over the past 20 years [9]
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