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Research ArticleInflammation/Infection
Open Access

First-in-Humans Study of 68Ga-DOTA-Siglec-9, a PET Ligand Targeting Vascular Adhesion Protein 1

Riikka Viitanen, Olli Moisio, Petteri Lankinen, Xiang-Guo Li, Mikko Koivumäki, Sami Suilamo, Tuula Tolvanen, Kirsi Taimen, Markku Mali, Ia Kohonen, Ilpo Koskivirta, Vesa Oikonen, Helena Virtanen, Kristiina Santalahti, Anu Autio, Antti Saraste, Laura Pirilä, Pirjo Nuutila, Juhani Knuuti, Sirpa Jalkanen and Anne Roivainen
Journal of Nuclear Medicine April 2021, 62 (4) 577-583; DOI: https://doi.org/10.2967/jnumed.120.250696
Riikka Viitanen
1Turku PET Centre, University of Turku, Turku, Finland
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Olli Moisio
1Turku PET Centre, University of Turku, Turku, Finland
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Petteri Lankinen
2Department of Orthopaedics and Traumatology, Turku University Hospital and University of Turku, Turku, Finland
3Turku PET Centre, Turku University Hospital, Turku, Finland
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Xiang-Guo Li
1Turku PET Centre, University of Turku, Turku, Finland
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Mikko Koivumäki
3Turku PET Centre, Turku University Hospital, Turku, Finland
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Sami Suilamo
4Department of Medical Physics, Turku University Hospital, Turku, Finland
5Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland
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Tuula Tolvanen
3Turku PET Centre, Turku University Hospital, Turku, Finland
4Department of Medical Physics, Turku University Hospital, Turku, Finland
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Kirsi Taimen
6Department of Rheumatology and Clinical Immunology, Division of Medicine, Turku University Hospital, Turku, Finland
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Markku Mali
6Department of Rheumatology and Clinical Immunology, Division of Medicine, Turku University Hospital, Turku, Finland
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Ia Kohonen
7Department of Radiology, Turku University Hospital, Turku, Finland
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Ilpo Koskivirta
6Department of Rheumatology and Clinical Immunology, Division of Medicine, Turku University Hospital, Turku, Finland
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Vesa Oikonen
1Turku PET Centre, University of Turku, Turku, Finland
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Helena Virtanen
1Turku PET Centre, University of Turku, Turku, Finland
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Kristiina Santalahti
8MediCity Research Laboratory, University of Turku, Turku, Finland; and
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Anu Autio
1Turku PET Centre, University of Turku, Turku, Finland
8MediCity Research Laboratory, University of Turku, Turku, Finland; and
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Antti Saraste
1Turku PET Centre, University of Turku, Turku, Finland
3Turku PET Centre, Turku University Hospital, Turku, Finland
9Heart Center, Turku University Hospital, Turku, Finland
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Laura Pirilä
6Department of Rheumatology and Clinical Immunology, Division of Medicine, Turku University Hospital, Turku, Finland
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Pirjo Nuutila
1Turku PET Centre, University of Turku, Turku, Finland
3Turku PET Centre, Turku University Hospital, Turku, Finland
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Juhani Knuuti
1Turku PET Centre, University of Turku, Turku, Finland
3Turku PET Centre, Turku University Hospital, Turku, Finland
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Sirpa Jalkanen
8MediCity Research Laboratory, University of Turku, Turku, Finland; and
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Anne Roivainen
1Turku PET Centre, University of Turku, Turku, Finland
3Turku PET Centre, Turku University Hospital, Turku, Finland
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  • FIGURE 1.
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    FIGURE 1.

    Whole-body coronal PET images of healthy volunteer (male; age, 29 y; weight, 74 kg; height, 183 cm) after intravenous injection of 167 MBq of 68Ga-DOTA-Siglec-9. Distribution of 68Ga-radioactivity 1–4 min after injection, based on imaging for 30 s per bed position, revealed high uptake, predominantly in heart, liver, kidneys, and ureter. At 20–36 min after injection and subsequent times, uptake was mainly in kidneys, ureter, and urinary bladder.

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    FIGURE 2.

    Decay-corrected time–activity curves of main organs. Result for urinary bladder in subject 6 was outlier so is presented separately. LV = left ventricle.

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    FIGURE 3.

    68Ga-DOTA-Siglec-9 and 18F-FDG PET/CT and MR images of hands of 49-y-old patient with early RA. Arrows denote proximal interphalangeal joints PIP2 and PIP3 and distal interphalangeal joint DIP3, whose time–activity curves are at bottom left. Respective SUVs were 1.05, 0.92, and 0.70 with 68Ga-DOTA-Siglec-9 and 1.46, 1.22. and 1.08 with 18F-FDG.

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    FIGURE 4.

    Representative radio-HPLC chromatograms of intact 68Ga-DOTA-Siglec-9 (A), human plasma 5 min after injection (B), and urine at 40 min after injection (C). In addition to parent tracer, several other peaks were detected in plasma, whereas in urine, radioactivity was entirely from radiometabolite.

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    FIGURE 5.

    (A and B) Total radioactivity (A) and proportion of parent tracer (B) decreased rapidly in blood circulation. (C) On average, 26% of radioactivity was bound to plasma proteins.

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    TABLE 1

    Normalized Number of Disintegrations (Hours) in Source Organs After Injection of 68Ga-DOTA-Siglec-9

    SiteMeanSDMinimumMaximum
    Bone, cortical0.02600.00450.01950.0312
    Bone, trabecular0.00390.00170.00250.0064
    Brain0.00470.00130.00330.0069
    Heart contents0.00330.00030.00300.0036
    Kidneys0.03590.01040.02310.0485
    Liver0.03770.00550.02660.0409
    Lungs0.01330.00330.01050.0176
    Pancreas0.00170.00040.00120.0021
    Red marrow0.00990.00190.00690.0127
    Salivary gland0.00050.00010.00050.0006
    Spleen0.00330.00040.00290.0040
    Urinary bladder0.32520.04260.26620.3831
    Remainder of body0.72570.09060.58610.8501
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    TABLE 2

    Dose-Equivalent Estimates (μSv/MBq) and Effective Dose (mSv/MBq) After Injection of 68Ga-DOTA-Siglec-9

    SiteMeanSDMinimumMaximum
    Adrenals12.21.410.714.2
    Brain2.40.51.93.3
    Colon, left8.30.87.29.3
    Colon, right8.40.87.39.4
    Esophagus6.90.85.98.0
    Eyes5.90.74.86.9
    Gallbladder wall8.70.97.79.8
    Heart wall11.51.310.013.3
    Kidneys54.414.936.072.5
    Liver12.71.69.413.7
    Lungs6.81.25.88.5
    Osteogenic cells9.91.28.411.7
    Pancreas8.51.46.810.0
    Prostate17.40.516.717.9
    Rectum14.10.114.014.3
    Red marrow8.60.87.710.0
    Salivary glands4.50.34.05.0
    Small intestine9.50.68.510.3
    Spleen12.81.211.514.6
    Stomach wall7.50.86.48.7
    Testes8.80.58.09.5
    Thymus6.80.85.78.0
    Thyroid6.70.85.57.8
    Urinary bladder wall383.248.5316.0449.0
    Whole body10.10.59.410.7
    Effective dose*0.0220.0020.0200.024
    • ↵* International Commission on Radiological Protection publication 103 (16).

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Journal of Nuclear Medicine: 62 (4)
Journal of Nuclear Medicine
Vol. 62, Issue 4
April 1, 2021
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First-in-Humans Study of 68Ga-DOTA-Siglec-9, a PET Ligand Targeting Vascular Adhesion Protein 1
Riikka Viitanen, Olli Moisio, Petteri Lankinen, Xiang-Guo Li, Mikko Koivumäki, Sami Suilamo, Tuula Tolvanen, Kirsi Taimen, Markku Mali, Ia Kohonen, Ilpo Koskivirta, Vesa Oikonen, Helena Virtanen, Kristiina Santalahti, Anu Autio, Antti Saraste, Laura Pirilä, Pirjo Nuutila, Juhani Knuuti, Sirpa Jalkanen, Anne Roivainen
Journal of Nuclear Medicine Apr 2021, 62 (4) 577-583; DOI: 10.2967/jnumed.120.250696

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First-in-Humans Study of 68Ga-DOTA-Siglec-9, a PET Ligand Targeting Vascular Adhesion Protein 1
Riikka Viitanen, Olli Moisio, Petteri Lankinen, Xiang-Guo Li, Mikko Koivumäki, Sami Suilamo, Tuula Tolvanen, Kirsi Taimen, Markku Mali, Ia Kohonen, Ilpo Koskivirta, Vesa Oikonen, Helena Virtanen, Kristiina Santalahti, Anu Autio, Antti Saraste, Laura Pirilä, Pirjo Nuutila, Juhani Knuuti, Sirpa Jalkanen, Anne Roivainen
Journal of Nuclear Medicine Apr 2021, 62 (4) 577-583; DOI: 10.2967/jnumed.120.250696
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Keywords

  • dosimetry
  • 68Ga
  • kinetics
  • PET
  • vascular adhesion protein 1
  • whole-body distribution
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