Improving contrast and detectability - imaging with [55Co]Co-DOTATATE in comparison with [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE

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Resumé

PET imaging at late time points post injection (p.i.) may allow tracer clearance from normal tissue and hence improve image contrast and detectability. 55Co is a promising isotope with high positron yield and a long half-life suitable for delayed time point imaging. Here, we compared the three radioconjugates [68Ga]Ga-DOTATATE, [64Cu]Cu-DOTATATE and [55Co]Co-DOTATATE by PET/CT imaging in NOD-SCID mice bearing subcutaneous somatostatin receptor expressing AR42J tumors. Methods:55Co and 64Cu were produced by the 54Fe(d,n)55Co and 64Ni(p,n)64Cu nuclear reactions while 68Ga was obtained from a 68Ge/68Ga generator. 55Co and 64Cu were labeled with DOTATATE by heating in a sodium acetate buffer and HEPES buffer, respectively. AR42J tumor-bearing mice were PET/CT scanned dynamically 0-1 h p.i. For 64Cu and 55Co additional late time point imaging after 4 h p.i. and 24 h p.i. were also performed. Dose calculations were performed based on a known biodistrubution. The cumulated disintegrations in each organ were calculated by integration of a fitted exponential function to the biodistribution of each respective organ. Equivalent dose calculations were hereafter calculated by OLINDA/EXM using the MIRD formalism. Results: Tumor uptake was rapid from 0 h p.i. to 1 h p.i. for all three radioconjugates. Normal tissue ratios as represented by tumor/liver, tumor/kidney and tumor/muscle ratios increased significantly over time with [55Co]Co-DOTATATE reaching the highest ratio of all radioconjugates. For [55Co]Co-DOTATATE, the tumor-to-liver ratio increased to 65±16 at 4 h and 50±6 at 24 h, which were 15 (p<0.001) and 30 (p<0.001) times higher, respectively, than the corresponding ratios for [64Cu]Cu-DOTATATE and 5 (p<0.001) times higher than that of [68Ga]Ga-DOTATATE at 1 h p.i. Correspondingly, tumor/kidney and tumor/muscle ratios for [55Co]Co-DOTATATE were 4 (p<0.001) and 11 (p<0.001) times higher than that of [64Cu]Cu-DOTATATE at 24 h p.i. An equivalent dose was calculated to 9.6E-02 mSv/MBq for [55Co]Co-DOTATATE. Conclusion: [55Co]Co-DOTATATE demonstrated superior image contrast compared to [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE for PET imaging of somatostatin receptor expressing tumors, warranting translation into clinical trials. Dosimetry calculations found comparable effective doses for [55Co]Co-DOTATATE compared to both [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE.

OriginalsprogEngelsk
TidsskriftJournal of nuclear medicine : official publication, Society of Nuclear Medicine
ISSN0161-5505
DOI
StatusE-pub ahead of print - 13. sep. 2019

Fingeraftryk

Neoplasms
Somatostatin Receptors
68Ga-DOTATATE
64Cu-DOTATATE
HEPES
Kidney
Sodium Acetate
Muscles
Inbred NOD Mouse
SCID Mice
Liver
Isotopes
Heating
Half-Life
Clinical Trials
Electrons

Citer dette

@article{72ee7627f9d7489aa6fd175d4920a84a,
title = "Improving contrast and detectability - imaging with [55Co]Co-DOTATATE in comparison with [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE",
abstract = "PET imaging at late time points post injection (p.i.) may allow tracer clearance from normal tissue and hence improve image contrast and detectability. 55Co is a promising isotope with high positron yield and a long half-life suitable for delayed time point imaging. Here, we compared the three radioconjugates [68Ga]Ga-DOTATATE, [64Cu]Cu-DOTATATE and [55Co]Co-DOTATATE by PET/CT imaging in NOD-SCID mice bearing subcutaneous somatostatin receptor expressing AR42J tumors. Methods:55Co and 64Cu were produced by the 54Fe(d,n)55Co and 64Ni(p,n)64Cu nuclear reactions while 68Ga was obtained from a 68Ge/68Ga generator. 55Co and 64Cu were labeled with DOTATATE by heating in a sodium acetate buffer and HEPES buffer, respectively. AR42J tumor-bearing mice were PET/CT scanned dynamically 0-1 h p.i. For 64Cu and 55Co additional late time point imaging after 4 h p.i. and 24 h p.i. were also performed. Dose calculations were performed based on a known biodistrubution. The cumulated disintegrations in each organ were calculated by integration of a fitted exponential function to the biodistribution of each respective organ. Equivalent dose calculations were hereafter calculated by OLINDA/EXM using the MIRD formalism. Results: Tumor uptake was rapid from 0 h p.i. to 1 h p.i. for all three radioconjugates. Normal tissue ratios as represented by tumor/liver, tumor/kidney and tumor/muscle ratios increased significantly over time with [55Co]Co-DOTATATE reaching the highest ratio of all radioconjugates. For [55Co]Co-DOTATATE, the tumor-to-liver ratio increased to 65±16 at 4 h and 50±6 at 24 h, which were 15 (p<0.001) and 30 (p<0.001) times higher, respectively, than the corresponding ratios for [64Cu]Cu-DOTATATE and 5 (p<0.001) times higher than that of [68Ga]Ga-DOTATATE at 1 h p.i. Correspondingly, tumor/kidney and tumor/muscle ratios for [55Co]Co-DOTATATE were 4 (p<0.001) and 11 (p<0.001) times higher than that of [64Cu]Cu-DOTATATE at 24 h p.i. An equivalent dose was calculated to 9.6E-02 mSv/MBq for [55Co]Co-DOTATATE. Conclusion: [55Co]Co-DOTATATE demonstrated superior image contrast compared to [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE for PET imaging of somatostatin receptor expressing tumors, warranting translation into clinical trials. Dosimetry calculations found comparable effective doses for [55Co]Co-DOTATATE compared to both [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE.",
author = "Andersen, {Thomas Lund} and Christina Baun and Olsen, {Birgitte Brinkmann} and Dam, {Johan Hygum} and Helge Thisgaard",
note = "Copyright {\circledC} 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.",
year = "2019",
month = "9",
day = "13",
doi = "10.2967/jnumed.119.233015",
language = "English",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine",

}

TY - JOUR

T1 - Improving contrast and detectability - imaging with [55Co]Co-DOTATATE in comparison with [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE

AU - Andersen, Thomas Lund

AU - Baun, Christina

AU - Olsen, Birgitte Brinkmann

AU - Dam, Johan Hygum

AU - Thisgaard, Helge

N1 - Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PY - 2019/9/13

Y1 - 2019/9/13

N2 - PET imaging at late time points post injection (p.i.) may allow tracer clearance from normal tissue and hence improve image contrast and detectability. 55Co is a promising isotope with high positron yield and a long half-life suitable for delayed time point imaging. Here, we compared the three radioconjugates [68Ga]Ga-DOTATATE, [64Cu]Cu-DOTATATE and [55Co]Co-DOTATATE by PET/CT imaging in NOD-SCID mice bearing subcutaneous somatostatin receptor expressing AR42J tumors. Methods:55Co and 64Cu were produced by the 54Fe(d,n)55Co and 64Ni(p,n)64Cu nuclear reactions while 68Ga was obtained from a 68Ge/68Ga generator. 55Co and 64Cu were labeled with DOTATATE by heating in a sodium acetate buffer and HEPES buffer, respectively. AR42J tumor-bearing mice were PET/CT scanned dynamically 0-1 h p.i. For 64Cu and 55Co additional late time point imaging after 4 h p.i. and 24 h p.i. were also performed. Dose calculations were performed based on a known biodistrubution. The cumulated disintegrations in each organ were calculated by integration of a fitted exponential function to the biodistribution of each respective organ. Equivalent dose calculations were hereafter calculated by OLINDA/EXM using the MIRD formalism. Results: Tumor uptake was rapid from 0 h p.i. to 1 h p.i. for all three radioconjugates. Normal tissue ratios as represented by tumor/liver, tumor/kidney and tumor/muscle ratios increased significantly over time with [55Co]Co-DOTATATE reaching the highest ratio of all radioconjugates. For [55Co]Co-DOTATATE, the tumor-to-liver ratio increased to 65±16 at 4 h and 50±6 at 24 h, which were 15 (p<0.001) and 30 (p<0.001) times higher, respectively, than the corresponding ratios for [64Cu]Cu-DOTATATE and 5 (p<0.001) times higher than that of [68Ga]Ga-DOTATATE at 1 h p.i. Correspondingly, tumor/kidney and tumor/muscle ratios for [55Co]Co-DOTATATE were 4 (p<0.001) and 11 (p<0.001) times higher than that of [64Cu]Cu-DOTATATE at 24 h p.i. An equivalent dose was calculated to 9.6E-02 mSv/MBq for [55Co]Co-DOTATATE. Conclusion: [55Co]Co-DOTATATE demonstrated superior image contrast compared to [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE for PET imaging of somatostatin receptor expressing tumors, warranting translation into clinical trials. Dosimetry calculations found comparable effective doses for [55Co]Co-DOTATATE compared to both [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE.

AB - PET imaging at late time points post injection (p.i.) may allow tracer clearance from normal tissue and hence improve image contrast and detectability. 55Co is a promising isotope with high positron yield and a long half-life suitable for delayed time point imaging. Here, we compared the three radioconjugates [68Ga]Ga-DOTATATE, [64Cu]Cu-DOTATATE and [55Co]Co-DOTATATE by PET/CT imaging in NOD-SCID mice bearing subcutaneous somatostatin receptor expressing AR42J tumors. Methods:55Co and 64Cu were produced by the 54Fe(d,n)55Co and 64Ni(p,n)64Cu nuclear reactions while 68Ga was obtained from a 68Ge/68Ga generator. 55Co and 64Cu were labeled with DOTATATE by heating in a sodium acetate buffer and HEPES buffer, respectively. AR42J tumor-bearing mice were PET/CT scanned dynamically 0-1 h p.i. For 64Cu and 55Co additional late time point imaging after 4 h p.i. and 24 h p.i. were also performed. Dose calculations were performed based on a known biodistrubution. The cumulated disintegrations in each organ were calculated by integration of a fitted exponential function to the biodistribution of each respective organ. Equivalent dose calculations were hereafter calculated by OLINDA/EXM using the MIRD formalism. Results: Tumor uptake was rapid from 0 h p.i. to 1 h p.i. for all three radioconjugates. Normal tissue ratios as represented by tumor/liver, tumor/kidney and tumor/muscle ratios increased significantly over time with [55Co]Co-DOTATATE reaching the highest ratio of all radioconjugates. For [55Co]Co-DOTATATE, the tumor-to-liver ratio increased to 65±16 at 4 h and 50±6 at 24 h, which were 15 (p<0.001) and 30 (p<0.001) times higher, respectively, than the corresponding ratios for [64Cu]Cu-DOTATATE and 5 (p<0.001) times higher than that of [68Ga]Ga-DOTATATE at 1 h p.i. Correspondingly, tumor/kidney and tumor/muscle ratios for [55Co]Co-DOTATATE were 4 (p<0.001) and 11 (p<0.001) times higher than that of [64Cu]Cu-DOTATATE at 24 h p.i. An equivalent dose was calculated to 9.6E-02 mSv/MBq for [55Co]Co-DOTATATE. Conclusion: [55Co]Co-DOTATATE demonstrated superior image contrast compared to [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE for PET imaging of somatostatin receptor expressing tumors, warranting translation into clinical trials. Dosimetry calculations found comparable effective doses for [55Co]Co-DOTATATE compared to both [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE.

U2 - 10.2967/jnumed.119.233015

DO - 10.2967/jnumed.119.233015

M3 - Journal article

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

ER -