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OtherBASIC SCIENCE INVESTIGATIONS

99mTc-Labeled Antimicrobial Peptides for Detection of Bacterial and Candida albicans Infections

Mick M. Welling, Antonella Lupetti, Henia S. Balter, Stella Lanzzeri, Beatriz Souto, Ana M. Rey, Eduardo O. Savio, Akke Paulusma-Annema, Ernest K.J. Pauwels and Peter H. Nibbering
Journal of Nuclear Medicine May 2001, 42 (5) 788-794;
Mick M. Welling
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Antonella Lupetti
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Henia S. Balter
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Stella Lanzzeri
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Beatriz Souto
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Ana M. Rey
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Eduardo O. Savio
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Akke Paulusma-Annema
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Ernest K.J. Pauwels
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Peter H. Nibbering
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  • FIGURE 1.
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    FIGURE 1.

    Typical scintigrams of 99mTc-labeled UBI 29–41 (A), hLF 1–11 (B), ciprofloxacin (C), and human polyclonal IgG (D) 1 h after injection into mice having thigh muscles infected with S. aureus.

  • FIGURE 2.
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    FIGURE 2.

    Accumulation of 99mTc-labeled antimicrobial peptide UBI 29–41 in thigh muscles of mice infected with MRSA (white bars), K. pneumoniae (square-hatched bars), or fluconazole-resistant C. albicans (black bars). Furthermore, mice were injected intramuscularly with LPS (diagonally hatched bars) or heat-killed bacteria (horizontally hatched bars) 18 h before administration of tracer. Each symbol at each time point represents mean ± SEM T/NT of at least 12 animals obtained from three independent experimental settings.

  • FIGURE 3.
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    FIGURE 3.

    Accumulation of 99mTc-labeled UBI 29–41 (white bars), UBI 18–35 (square-hatched bars), hLF 1–11 (horizontally hatched bars), ciprofloxacin (black bars), and IgG (checkered bars) in thigh muscles of mice infected 18 h earlier with fluconazole-resistant C. albicans. Each symbol at each time point represents mean ± SEM T/NT of at least six animals obtained from three independent experimental settings.

  • FIGURE 4.
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    FIGURE 4.

    Typical scintigrams of 99mTc-labeled UBI 29–41 (A), hLF 1–11 (B), ciprofloxacin (C), and human polyclonal IgG (D) 1 h after injection into mice having thigh muscles injected with heat-killed S. aureus.

  • FIGURE 5.
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    FIGURE 5.

    (A) Typical scintigram of 99mTc-labeled UBI 29–41 1 h after injection into rabbits with thigh muscles infected with S. aureus. (B) Biodistribution of 99mTc-labeled UBI 29–41 1 h after injection with lower contrast.

  • FIGURE 6.
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    FIGURE 6.

    Accumulation of 99mTc-labeled UBI 29–41 in thigh muscles of rabbits injected with MRSA (white bars), K. pneumoniae (square-hatched bars), heat-killed MRSA (diagonally hatched bars), heat-killed K. pneumoniae (horizontally hatched bars), or 50 mg LPS (black bars). Each symbol at each time point represents mean ± SEM T/NT of at least three animals obtained from independent experimental settings.

Tables

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    TABLE 1

    Antimicrobial Agents Used in This Study

    Antimicrobial compoundAmino acidsAmino acid sequenceCode
    UBI (21)29–41TGRAKRRMQYNRRUBI 29–41
    18–35KVAKQEKKKKKTGRAKRRUBI 18–35
    31–38RAKRRMQYUBI 31–38
    hLF 1–11GRRRRSVQWCAhLF 1–11
     4–11RRSVQWCAhLF 4–11
    21–31FQWQRNMRKVRhLF 21–31
    Defensin (22) 1–43—HNP-1–3
    Ciprofloxacin——Ciprofloxacin
    IgG——IgG
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    TABLE 2

    Mean T/NT of Infected/Inflamed Thigh Muscles After Injection of 99mTc-Labeled Compounds

    99mTc-labeled compoundS. aureus and MRSAK. pneumoniaeC. albicansSterile inflammation
    LPSHeat-killed microorganisms
    UBI 29–413.3  ±  0.2 (21)*2.3 ± 0.1 (21)*2.8  ±  0.2 (14)*1.4  ±  0.1 (12)1.4  ±  0.1 (12)
    UBI 18–352.4  ±  0.1 (33)*2.7 ± 0.2 (16)*2.7  ±  0.3 (8)*1.0  ±  0.1 (22)1.2  ±  0.1 (18)
    UBI 31–383.7  ±  0.4 (6)*2.0 ± 0.1 (8)*ND1.1  ±  0.1 (6)ND
    hLF 1–112.5  ±  0.2 (12)*ND3.4  ±  0.3 (8)*1.1  ±  0.1 (12)1.4  ±  0.1 (6)
    hLF 4–111.7  ±  0.2 (6)NDND1.6  ±  0.2 (6)ND
    hLF 21–314.1  ±  0.7 (6)*ND2.4  ±  0.4 (6)*1.4  ±  0.1 (6)ND
    HNP-1–32.4  ±  0.2 (32)*1.9 ± 0.1 (22)*3.2  ±  0.5 (6)*1.0  ±  0.1 (6)ND
    Ciprofloxacin1.8  ±  0.1 (6)1.7 ± 0.1 (6)2.6  ±  0.2 (15)*2.0  ±  0.1 (8)1.7  ±  0.2 (6)
    IgG2.5  ±  0.2 (31)2.0 ± 0.3 (22)4.2  ±  0.3 (6)*2.1  ±  0.2 (8)2.0  ±  0.1 (14)
    • ↵* T/NT is significantly higher (P < 0.05) than T/NT in mice injected with LPS or heat-killed microorganisms.

    • ND = not done.

    • Values are mean ± SEM T/NT observed at 30, 60, and 120 min after injection of tracer. The number of animals is given in parentheses.

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Journal of Nuclear Medicine
Vol. 42, Issue 5
May 1, 2001
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99mTc-Labeled Antimicrobial Peptides for Detection of Bacterial and Candida albicans Infections
Mick M. Welling, Antonella Lupetti, Henia S. Balter, Stella Lanzzeri, Beatriz Souto, Ana M. Rey, Eduardo O. Savio, Akke Paulusma-Annema, Ernest K.J. Pauwels, Peter H. Nibbering
Journal of Nuclear Medicine May 2001, 42 (5) 788-794;

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99mTc-Labeled Antimicrobial Peptides for Detection of Bacterial and Candida albicans Infections
Mick M. Welling, Antonella Lupetti, Henia S. Balter, Stella Lanzzeri, Beatriz Souto, Ana M. Rey, Eduardo O. Savio, Akke Paulusma-Annema, Ernest K.J. Pauwels, Peter H. Nibbering
Journal of Nuclear Medicine May 2001, 42 (5) 788-794;
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