title: [(68)Ga]NODAGA-RGD - Metabolic stability, biodistribution, and dosimetry data from patients with hepatocellular carcinoma and liver cirrhosis.
abstract: OBJECTIVE
  This study was designed to determine safety, tolerability, and radiation burden of a [(68)Ga]NODAGA-RGD-PET for imaging integrin αvβ3 expression in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Moreover, metabolic stability and biokinetic data were compiled.
  
  
  METHODS
  After injection of 154-184 MBq [(68)Ga]NODAGA-RGD three consecutive PET/CT scans were acquired starting 8.3 ± 2.1, 36.9 ± 2.8, and 75.1 ± 3.4 min after tracer injection. For metabolite analysis, blood and urine samples were analyzed by HPLC. For dosimetry studies, residence time VOIs were placed in the corresponding organs. The OLINDA/EXM program was used to estimate the absorbed radiation dose.
  
  
  RESULTS
  The radiopharmaceutical was well tolerated and no drug-related adverse effects were observed. No metabolites could be detected in blood (30 and 60 min p.i.) and urine (60 min p.i.). [(68)Ga]NODAGA-RGD showed rapid and predominantly renal elimination. Background radioactivity in blood, intestine, lung, and muscle tissue was low (%ID/l 60 min p.i. was 0.56 ± 0.43, 0.54 ± 0.39, 0.22 ± 0.05, and 0.16 ± 0.8, respectively). The calculated effective dose was 21.5 ± 5.4 μSv/MBq, and the highest absorbed radiation dose was found for the urinary bladder wall (0.26 ± 0.09 mSv/MBq). No increased uptake of the tracer was found in HCC compared with the background liver tissue.
  
  
  CONCLUSIONS
  [(68)Ga]NODAGA-RGD uptake in the HCCs lesions was not sufficient to use this tracer for imaging these tumors. [(68)Ga]NODAGA-RGD was well tolerated and metabolically stable. Due to rapid renal excretion, background radioactivity was low in most of the body, resulting in low radiation burden and indicating the potential of [(68)Ga]NODAGA-RGD PET for non-invasive determination of integrin αvβ3 expression.
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria. roland.haubner@i-med.ac.at.
authors.forename: Roland
authors.initials: R
authors.lastname: Haubner
authors.affiliation: Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Armin
authors.initials: A
authors.lastname: Finkenstedt
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.|FH Gesundheit/University of Applied Sciences Tyrol, Innsbruck, Austria.
authors.forename: Armin
authors.initials: A
authors.lastname: Stegmayr
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Rangger
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Decristoforo
authors.affiliation: Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Zoller
authors.affiliation: Department of Nuclear Medicine, Medical University of Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Virgolini
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000378:metabolism*; D056831:Coordination Complexes / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D009928:Organ Specificity; D010456:Peptides, Cyclic / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D011829:Radiation Dosage; D000069079:Radiation Exposure / Q000032:analysis*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014915:Whole-Body Counting
chemical_list: C561299:68Ga-NODAGA-RGD; D056831:Coordination Complexes; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals
keywords: Dosimetry; Hepatocellular carcinoma; Metabolic stability; PET; Whole-body distribution; [68Ga]NODAGA-RGD