Research ArticleClinical Investigations

Phase-1 Clinical Trial Results of High-Specific-Activity Carrier-Free 123I-Iobenguane

Bennett B. Chin, James F. Kronauge, Frank J. Femia, Jianqing Chen, Kevin P. Maresca, Shawn Hillier, Neil A. Petry, Olga G. James, Jorge D. Oldan, Thomas Armor, James B. Stubbs, Michael G. Stabin and John W. Babich
Journal of Nuclear Medicine May 2014, 55 (5) 765-771; DOI: https://doi.org/10.2967/jnumed.113.124057

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Synthetic pathway used in production of high-purity 123I-iobenguane.

  • FIGURE 2.
    FIGURE 2.

    Anterior whole-body images in healthy man at 0.25 h (A), 1 h (B), 4 h (C), and 24 h (D) after injection of HSA 123I-iobenguane (48-h postinjection images are not shown; calibration standard is located at right foot).

  • FIGURE 3.
    FIGURE 3.

    Anterior whole-body images in healthy woman at 0.25 h (A), 1 h (B), 4 h (C), and 24 h (D) after injection of HSA 123I-iobenguane (48-h postinjection images are not shown; calibration standard is located at right foot).

  • FIGURE 4.
    FIGURE 4.

    Representative mid-ventricular HSA 123I-iobenguane SPECT images in healthy 33-y-old woman. (Top) Early SPECT short-axis (left), vertical long-axis (middle), and horizontal long-axis (right) images. (Bottom) Corresponding delayed SPECT images in same orientations.

Tables

  • TABLE 1

    Summarized High-Performance Liquid Chromatography/Mass Spectrometry Concentrations of Iobenguane and Related Chemical Species for HSA 123I-Iobenguane (n = 6)

    Parameter123I-MIBG127I-MIBGAll MIBG*mHBG†BG‡All API species
    Content (ng/mL)4.7 ± 3.1§9.6 ± 9.1§14.313.2 ± 3.0§362.8 ± 55.1§390.3
    Content (nmol/mL)0.01730.03480.0520.07952.41872.55
    Specific activity dose
     GBq/μmol5,353.32,659.41,775.81,163.238.236.26
     mCi/μmol144,68471,87647,99431,4391,033980.4║

    • ↵* Molecular weight = 272 or 276.

    • ↵† Molecular weight = 166.

    • ↵‡ Molecular weight = 150.

    • ↵§ Sample SD = σxn-1 and N equals degrees of freedom.

    • ↵║ Apparent specific activity.

    • mHBG = meta-hydroxybenzylguanidine; BG = benzylguanidine; API = active pharmaceutical ingredient.

  • TABLE 2

    HSA 123I-Iobenguane Pharmacokinetic Parameters in Healthy Adult Humans

    ParameterWomen (n = 6)Men (n = 6)All subjects
    Tmax (h)0.20 ± 0.110.25 ± 0.120.22 ± 0.12
    Peak plasma concentration (Bq/mL)3,034 ± 1,5542,553 ± 1,6282,886 ± 1,665
    Area under curve, 0–∞ (h × MBq/mL)0.15 ± 0.040.08 ± 0.040.11 ± 0.06
    Clearance (mL/h/kg)30.3 ± 7.1682.8 ± 58.458.1 ± 50.2
    Steady-state volume of distribution (mL/kg)3,993 ± 923.65,550 ± 810.24,853 ± 1,180
    t½ (h)93.9 ± 15.861.4 ± 25.578.4 ± 27.5
    Mean residence time, 0–∞ (h)133.4 ± 22.5285.94 ± 36.31110.7 ± 39.7
    t½ α (h)0.21 ± 0.09*0.24 ± 0.100.22 ± 0.09
    t½ β (h)101.7 ± 32.1*59.6 ± 20.678.7 ± 33.3
    Urine (% injected dose at 24 h)51.8 ± 8.7955.7 ± 10.553.7 ± 9.46
    Urine (% injected dose at 48 h)65.5 ± 12.369.1 ± 11.867.3 ± 11.6

    • ↵* n = 5 for this value because data were not calculated for first female subject.

  • TABLE 3

    Descriptive Statistics for Radiation Dose Estimates (mGy/MBq) from HSA 123I-Iobenguane Distribution in 12 Healthy Adults

    SiteMeanMinimumMaximumSDCOV
    Urinary bladder wall7.3E−024.6E−028.6E−021.1E−0215%
    Lower large intestine wall7.1E−024.9E−029.6E−021.2E−0217%
    Salivary glands6.4E−023.5E−028.8E−021.4E−0221%
    Upper large intestine wall6.3E−024.3E−028.4E−021.0E−0217%
    Thyroid5.5E−023.9E−027.6E−029.4E−0317%
    Small intestine3.1E−022.3E−023.9E−024.0E−0313%
    Kidneys2.8E−022.3E−024.9E−027.0E−0325%
    Liver2.7E−022.2E−023.3E−023.8E−0314%
    Heart wall2.7E−021.9E−023.1E−023.3E−0312%
    Osteogenic cells2.4E−022.2E−022.7E−021.7E−037%
    Ovaries2.2E−021.8E−022.6E−022.0E−039%
    Uterus1.9E−021.7E−022.1E−029.7E−045%
    Gallbladder wall1.7E−021.6E−021.9E−027.0E−044%
    Spleen1.6E−021.3E−022.0E−021.9E−0312%
    Lungs1.5E−021.1E−021.8E−021.9E−0312%
    Pancreas1.2E−021.1E−021.3E−027.4E−046%
    Adrenals1.2E−021.1E−021.3E−028.7E−047%
    Stomach wall1.1E−021.0E−021.2E−025.6E−045%
    Muscle8.8E−038.3E−039.5E−033.9E−044%
    Red marrow8.7E−038.1E−039.3E−034.0E−045%
    Thymus8.5E−037.4E−039.3E−036.3E−047%
    Testes8.4E−037.9E−039.1E−033.4E−044%
    Breasts6.1E−035.4E−036.6E−034.5E−047%
    Skin5.3E−034.8E−035.9E−033.4E−046%
    Brain4.0E−033.7E−034.6E−033.0E−048%
    Total body1.0E−029.8E−031.1E−024.2E−044%
    Effective dose (mSv/MBq)2.7E−022.3E−023.0E−021.9E−037%

    • COV = coefficient of variation.

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