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Research ArticleBasic Science Investigations

Preclinical Evaluation of 68Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging

Thomas Ebenhan, Jan Rijn Zeevaart, Jacobus D. Venter, Thavendran Govender, Gert H. Kruger, Neil V. Jarvis and Mike M. Sathekge
Journal of Nuclear Medicine February 2014, 55 (2) 308-314; DOI: https://doi.org/10.2967/jnumed.113.128397
Thomas Ebenhan
1Department of Nuclear Medicine, University of Pretoria and Steve Biko Academic Hospital, Pretoria, South Africa
2School of Chemistry, University of KwaZulu Natal, Durban, South Africa
3Research and Development, The South African Nuclear Energy Corporation, Pelindaba, Pretoria, South Africa
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Jan Rijn Zeevaart
4Department of Science and Technology, Preclinical Drug Development Platform, North West University, Potchefstroom, South Africa
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Jacobus D. Venter
5Medical Research Council of South Africa, Pretoria, South Africa; and
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Thavendran Govender
6Unit Catalysis, University of KwaZulu Natal, Durban, South Africa
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Gert H. Kruger
2School of Chemistry, University of KwaZulu Natal, Durban, South Africa
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Neil V. Jarvis
3Research and Development, The South African Nuclear Energy Corporation, Pelindaba, Pretoria, South Africa
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Mike M. Sathekge
1Department of Nuclear Medicine, University of Pretoria and Steve Biko Academic Hospital, Pretoria, South Africa
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  • FIGURE 1.
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    FIGURE 1.

    Coronal PET images acquired at 60 min after intravenous injection of 48–155 MBq of 68Ga-NOTA-UBI29-41 into healthy rabbits (NZR-1) (A) and 37–174 MBq of 68Ga-NOTA-UBI29-41 into rabbits with muscular infection (right thigh) and with sterile muscular inflammation muscle (left thigh) (NZR-2) (B). Axial PET/CT images displaying hind thighs 5 (C), 30 (D), 60 (E), and 90 (F) min after injection.

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    FIGURE 2.

    Activity concentration of 68Ga-NOTA-UBI29-41 in blood (A) and urine (B) obtained from healthy rabbits (group NZR-1). Animals were injected intravenously with 96 ± 35 MBq/kg.

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    TABLE 1

    Organ and Tissue Biodistribution of 68Ga-NOTA-UBI29-41 in Healthy Rabbits

    Percentage of injected dose (min) after injection*
    Organ or tissue3060120
    Heart0.66 ± 0.170.63 ± 0.310.55 ± 0.06
    Liver5.71 ± 2.433.82 ± 0.922.24 ± 0.96
    Spleen1.08 ± 0.520.73 ± 0.310.75 ± 0.09
    Bladder, urinary tract25.10 ± 6.0927.55 ± 6.5033.09 ± 7.24
    Kidney2.86 ± 1.104.23 ± 1.653.17 ± 0.71
    Hind leg muscle0.12 ± 0.050.10 ± 0.030.11 ± 0.02
    Front leg muscle0.11 ± 0.040.10 ± 0.030.10 ± 0.02
    Lung0.42 ± 0.180.46 ± 0.160.41 ± 0.06
    Brain0.05 ± 0.020.05 ± 0.020.06 ± 0.02
    • ↵* Values represent mean ± SD of n > 3 animals.

    • View popup
    TABLE 2

    Organ and Tissue Concentration of 68Ga-NOTA-UBI29-41 in Healthy Rabbits

    SUV (min) after injection*
    Organ or tissue3060120
    Heart0.80 ± 0.240.65 ± 0.160.53 ± 0.24
    Liver1.91 ± 1.171.84 ± 1.320.67 ± 0.27
    Spleen1.65 ± 0.861.62 ± 0.950.74 ± 0.29
    Bladder, urinary tract19.96 ± 8.4714.16 ± 4.2410.65 ± 4.90
    Kidney3.20 ± 0.883.39 ± 0.742.85 ± 0.63
    Hind leg muscle0.25 ± 0.080.20 ± 0.040.12 ± 0.02
    Front leg muscle0.24 ± 0.050.20 ± 0.050.10 ± 0.03
    Lung0.60 ± 0.220.53 ± 0.220.35 ± 0.10
    Brain0.24 ± 0.110.16 ± 0.070.13 ± 0.07
    • ↵* Values represent mean ± SD of n > 3 animals.

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    TABLE 3

    Accumulation of 68Ga-NOTA-UBI29-41 in Staphylococcus Aureus–Infected Rabbits

    PET/CT image acquisition (min) after injection†
    T/NT* ratio5306090
    Normal hind muscle to normal front muscle1.02‡0.99 ± 0.171.02 ± 0.19ND
    Infected muscle to normal muscle3.16 ± 0.893.16 ± 0.754.35 ± 0.853.84 ± 1.53
    Inflamed muscle to normal muscle1.12 ± 0.141.12 ± 0.071.25 ± 0.250.98 ± 0.19
    Infected muscle to inflamed muscle2.86 ± 0.932.90 ± 0.503.54 ± 0.863.80 ± 0.90
    Infected muscle to liver0.97 ± 0.100.97 ± 0.521.35 ± 0.330.81 ± 0.59
    • ↵* Nontargeted tissue (frontal leg triceps).

    • ↵† Values represent mean ± SD of > 3 animals/group.

    • ↵‡ Lung-to-muscle ratio calculated from single animal.

    • ND = value not determined.

    • View popup
    TABLE 4

    Pulmonary Distribution of 68Ga-NOTA-UBI29-41 in Rabbits: Quantification of Lung Tissue

    PET/CT image acquisition (min) after injection†
    T/NT* ratio (lung to muscle)5306090120
    Healthy (NZR-1)ND2.5 ± 0.632.5 ± 0.53ND3.0 ± 0.55
    Infection/inflammation (NZR-2)1.9 ± 0.532.5 ± 0.792.2 ± 0.492.7 ± 1.01ND
    Asthma (NZR-3)2.1‡2.4 ± 0.452.5 ± 0.44NDND
    • ↵* Nontargeted tissue (frontal leg triceps).

    • ↵† Values represent mean ± SD of > 3 animals/group.

    • ↵‡ Lung-to-muscle ratio calculated from single animal.

    • ND = value not determined.

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Journal of Nuclear Medicine: 55 (2)
Journal of Nuclear Medicine
Vol. 55, Issue 2
February 1, 2014
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Preclinical Evaluation of 68Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging
Thomas Ebenhan, Jan Rijn Zeevaart, Jacobus D. Venter, Thavendran Govender, Gert H. Kruger, Neil V. Jarvis, Mike M. Sathekge
Journal of Nuclear Medicine Feb 2014, 55 (2) 308-314; DOI: 10.2967/jnumed.113.128397

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Preclinical Evaluation of 68Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging
Thomas Ebenhan, Jan Rijn Zeevaart, Jacobus D. Venter, Thavendran Govender, Gert H. Kruger, Neil V. Jarvis, Mike M. Sathekge
Journal of Nuclear Medicine Feb 2014, 55 (2) 308-314; DOI: 10.2967/jnumed.113.128397
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Keywords

  • 68Ga labeling
  • ubiquicidin
  • infection
  • UBI29-41
  • PET/CT imaging
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