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Abstract

⁶⁸Ga labeled NOTA-RGD was a recently developed positron emission tomography (PET) radiotracer for the visualization of angiogenesis, and is regarded as a promising imaging agent for cancer and several other disorders. In this study, we investigated the whole-body distribution and radiation dosimetry of ⁶⁸Ga-NOTA-RGD in humans. Ten cancer patients (53.7±13.5 years; 61.5±7.4 kg) participated in this study. PET scans were performed using a PET/computed tomography (scanner in three-dimensional mode). After an intravenous injection of 172.4±20.5 MBq of ⁶⁸Ga-NOTA-RGD, eight serial whole-body scans were performed during 90 minutes. Volumes of interest were drawn manually over the entire volumes of the urinary bladder, the gallbladder, heart, kidneys, liver, lungs, pancreas, spleen, and stomach. Time-activity curves were obtained from serial PET scan data. Residence times were calculated from areas under curve of time-activity curves and used as input to the OLINDA/EXM 1.1 software. The uptake of ⁶⁸Ga-NOTA-RGD was highest in the kidneys and urinary bladder. Radiation doses to kidneys and urinary bladder were 71.6±28.4 μGy/MBq and 239.6±56.6 μGy/MBq. Mean effective doses were 25.0±4.4 μSv/MBq using International Commission of Radiation Protection (ICRP) publication 60 and 22.4±3.8 μSv/MBq using ICRP publication 103 weighting factor. We evaluated the radiation dosimetry of ⁶⁸Ga labeled NOTA-RGD, which has an acceptable effective radiation dose.

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References

Veikkola

, Karkkainen

, Claesson-Welsh

et al. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res, 2000; 60:203.

Carmeliet

. Angiogenesis in life, disease and medicine. Nature, 2005; 438:932.

Ferrara

, Kerbel

. Angiogenesis as a therapeutic target. Nature, 2005; 438:967.

Guo

, Giancotti

. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol, 2004; 5:816.

Brooks

, Montgomery

, Rosenfeld

et al. Integrin α_vβ₃ antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell, 1994; 79:1157.

Hood

, Cheresh

. Role of integrins in cell invasion and migration. Nat Rev Cancer, 2002; 2:91.

Ruoslahti

. Specialization of tumour vasculature. Nat Rev Cancer, 2002; 2:83.

Haubner

, Beer

, Wang

et al. Positron emission tomography tracers for imaging angiogenesis. Eur J Nucl Med Mol Imaging, 2010; 37,Suppl:S86.

Yang

, Guo

, Miao

. Technetium-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptides for human melanoma imaging. Nucl Med Biol, 2010; 37:873.

10.

Yan

, Chen

, Yang

et al. A new ¹⁸F-labeled BBN-RGD peptide heterodimer with a symmetric linker for prostate cancer imaging. Amino Acids, 2011; 41:439.

11.

Picchio

, Beck

, Haubner

et al. Intratumoral spatial distribution of hypoxia and angiogenesis assessed by ¹⁸F-FAZA and ¹²⁵I-Gluco-RGD autoradiography. J Nucl Med, 2008; 49:597.

12.

Liu

, Yan

, Liu

et al. ¹⁸F, ⁶⁴Cu, and ⁶⁸Ga labeled RGD-bombesin heterodimeric peptides for PET imaging of breast cancer. Bioconjug Chem, 2009; 20:1016.

13.

Yoshimoto

, Ogawa

, Washiyama

et al. α_vβ₃ Integrin-targeting radionuclide therapy and imaging with monomeric RGD peptide. Int J Cancer, 2008; 123:709.

14.

Beer

, Haubner

, Wolf

et al. PET-based human dosimetry of ¹⁸F-galacto-RGD, a new radiotracer for imaging αvβ3 expression. J Nucl Med, 2006; 47:763.

15.

McParland

, Miller

, Spinks

et al. The biodistribution and radiation dosimetry of the Arg-Gly-Asp peptide ¹⁸F-AH111585 in healthy volunteers. J Nucl Med, 2008; 49:1664.

16.

Jeong

, Hong

, Chang

et al. Preparation of a promising angiogenesis PET imaging agent: ⁶⁸Ga-labeled c(RGDyK)-isothiocyanatobenzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid and feasibility studies in mice. J Nucl Med, 2008; 49:830.

17.

Breeman

, Verbruggen

. The ⁶⁸Ge/⁶⁸Ga generator has high potential, but when can we use ⁶⁸Ga-labelled tracers in clinical routine? Eur J Nucl Med Mol Imaging, 2007; 34:978.

18.

Shetty

, Lee

, Jeong

. ⁶⁸Ga-labeled radiopharmaceuticals for positron emission tomography. Nucl Med Mol Imaging, 2010; 44:233.

19.

Ehrhardt

, Welch

. A new germanium-68/gallium-68 generator. J Nucl Med, 1978; 19:925.

20.

Kolbert

, Pentlow

, Pearson

et al. Prediction of absorbed dose to normal organs in thyroid cancer patients treated with ¹³¹I by use of ¹²⁴I PET and 3-dimensional internal dosimetry software. J Nucl Med, 2007; 48:143.

21.

Antenor-Dorsey

, Laforest

, Moerlein

et al. Radiation dosimetry of N-([¹¹C]methyl)benperidol as determined by whole-body PET imaging of primates. Eur J Nucl Med Mol Imaging, 2008; 35:771.

22.

Stabin

, Sparks

, Crowe

. OLINDA/EXM: The second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med, 2005; 46:1023.

23.

Treyer

, Streffer

, Ametamey

et al. Radiation dosimetry and biodistribution of 11C-ABP688 measured in healthy volunteers. Eur J Nucl Med Mol Imaging, 2008; 35:766.

24.

Nye

, Schuster

, Yu

et al. Biodistribution and radiation dosimetry of the synthetic nonmetabolized amino acid analogue anti-¹⁸F-FACBC in humans. J Nucl Med, 2007; 48:1017.

25.

Thomas

, Stabin

, Chen

et al. MIRD Pamphlet No. 14 revised: A dynamic urinary bladder model for radiation dose calculations. J Nucl Med, 1999; 40:102S.

26.

Hirvonen

, Roivainen

, Virta

et al. Human biodistribution and radiation dosimetry of ¹¹C-(R)-PK11195, the prototypic PET ligand to image inflammation. Eur J Nucl Med Mol Imaging, 2010; 37:606.

27.

Hartmann

, Zöphel

, Freudenberg

et al. Radiation exposure of patients during ⁶⁸Ga-DOTATOC PET/CT examinations. Nuklearmedizin, 2009; 48:201.

28.

Pettinato

, Sarnelli

, Di Donna

et al. ⁶⁸Ga-DOTANOC: Biodistribution and dosimetry in patients affected by neuroendocrine tumors. Eur J Nucl Med Mol Imaging, 2008; 35:72.

29.

Scheinin

, Tolvanen

, Wilson

et al. Biodistribution and radiation dosimetry of the amyloid imaging agent ¹¹C-PIB in humans. J Nucl Med, 2007; 48:128.

30.

Seltzer

, Jahan

, Sparks

et al. Radiation dose estimates in humans for ¹¹C-acetate whole-body PET. J Nucl Med, 2004; 45:1233.

31.

Slifstein

, Hwang

, Martinez

et al. Biodistribution and radiation dosimetry of the dopamine D₂ ligand ¹¹C-raclopride determined from human whole-body PET. J Nucl Med, 2006; 47:313.

32.

Leide-Svegborn

. Radiation exposure of patients and personnel from a PET/CT procedure with ¹⁸F-FDG. Radiat Prot Dosimetry, 2010; 139:208.

33.

Lin

, Weng

, Wey

et al. Whole-body biodistribution and radiation dosimetry of ¹⁸F-FP-(+)-DTBZ (¹⁸F-AV-133): A novel vesicular monoamine transporter 2 imaging agent. J Nucl Med, 2010; 51:1480.

34.

Koole

, Lewis

, Buckley

et al. Whole-body biodistribution and radiation dosimetry of ¹⁸F-GE067: A radioligand for in vivo brain amyloid imaging. J Nucl Med, 2009; 50:818.

Whole-Body Distribution and Radiation Dosimetry of 68 Ga-NOTA-RGD,a Positron Emission Tomography Agent for Angiogenesis Imaging

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