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Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study

Gian Luca Poli, Claudia Bianchi, Giorgio Virotta, Anna Bettini, Renzo Moretti, Eveline Trachsel, Giuliano Elia, Leonardo Giovannoni, Dario Neri and Andrea Bruno
Gian Luca Poli
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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Claudia Bianchi
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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Giorgio Virotta
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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Anna Bettini
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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Renzo Moretti
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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Eveline Trachsel
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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Giuliano Elia
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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Leonardo Giovannoni
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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Dario Neri
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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Andrea Bruno
1Azienda Ospedaliera Papa Giovanni XXIII, Bergamo; 2Philogen S.p.A., Siena, Italy; 3Philochem AG, Otelfingen; and 4Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
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DOI: 10.1158/2326-6066.CIR-13-0007 Published August 2013
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  • Figure 1.
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    Figure 1.

    124I PET/CT calibration. A, NEMA IEC Body Phantom PET acquisitions with 124I for spheres to background activity concentration ratios equal to infinite, 9, 5, and 3, conducted to obtain the recovery coefficients (RC; see Materials and Methods) for dosimetric calculations. B, course of the recovery coefficients as a function of sphere volume represented for different S:B concentration ratios.

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    Figure 2.

    Bone red marrow dosimetry. A, time course of FIA/mL 131I in the blood of patients during the diagnostic (solid lines) and posttherapy phase (dashed lines). B, time course of FIA (131I) in the body of patients during the diagnostic and posttherapy phase. 124I diagnostic data are rescaled to 131I half time. Different colors refer to different patients.

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    Figure 3.

    Examples of imaging data in patients. A, 124I-L19SIP PET image 24 hours p.i., showing a hepatic lesion with high antibody uptake. The corresponding transaxial, sagittal, and coronal projections PET/CT fusion images are depicted in B. C, FDG PET image of a lesion in the cerebellar region, visible despite the high metabolic uptake of glucose in the brain (transaxial, sagittal, and coronal projections); the corresponding PET images stemming from the diagnostic phase with 124I-L19SIP (24 hours p.i.) and SPECT images posttherapy from the use of 131I-L19SIP (24 hours p.i.) are depicted in D and E, respectively.

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    Figure 4.

    Lesions and healthy organs dosimetry. A, time course of FIA/g of tissue in selected brain lesions (dotted lines) and extracranial metastases (continuous lines) of all 6 patients. *, values for extracranial (liver) and brain lesions measured in the same patient. B, FIA/g of tissue time course in various organs from one patient. The 124I diagnostic values have been rescaled to match the physical half-life of 131I (8 days). The profiles thus represent an underestimate of the antibody residence on the lesion, as they contain an exponential component for the decay of the radionuclide.

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  • Table 1.

    Estimated doses to healthy organs, brain lesions, and extracranial metastases

    Organ/lesionDmean, Gy/GBqRange, Gy/GBq
    Adrenals0.1920.153–0.229
    Brain0.0760.064–0.086
    Breasts0.1420.113–0.173
    Gall bladder wall0.1940.158–0.232
    Lower large intestine wall0.1780.144–0.221
    Small intestine0.1780.149–0.213
    Stomach wall0.1780.143–0.218
    Upper large intestine wall0.1820.147–0.225
    Heart wall0.2050.107–0.318
    Kidneys0.5530.397–0.791
    Liver0.2970.229–0.346
    Lungs0.3400.224–0.293
    Muscle0.1570.127–0.193
    Ovaries0.2040.188–0.224
    Pancreas0.1950.156–0.235
    Bone red marrow0.2010.168–0.256
    Osteogenic cells0.3260.257–0.411
    Skin0.1320.106–0.163
    Spleen0.2970.172–0.413
    Testes0.1330.124–0.143
    Thymus0.1690.133–0.204
    Thyroid2.6480.807–5.650
    Urinary bladder wall0.1680.142–0.201
    Uterus0.2020.187–0.222
    Total body0.1710.138–0.206
    Effective dose0.3150.220–0.481
    Brain lesions0.3760.099–1.370
    Extracranial lesions1.4080.153–5.380

    NOTE: The dose of radioactivity to the various organs (normalized per GBq of administered 131I-labeled antibody) was calculated as described in the Materials and Methods. Please note the large range of values in the brain and extracranial lesions, which are in stark contrast with the extremely narrow range observed for the normal organs. The high variability observed for the thyroid reflects a poor compliance of patients for their premedication with Lugol solution during the diagnostic phase of the study.

    • Table 2.

      Estimated doses to individual lesions

      MassAvg. doseAvg. dose
      PatientLesiongGy/GBqGy
      1Brain, left frontal22.80.201.48
      Brain, right occipital23.10.241.75
      Lung, right upper lobe0.80.151.11
      2Brain, cerebellar vermis13.70.664.41
      Brain, left lower temporomedial0.40.432.83
      Liver27.05.3835.84
      3Brain, right anterior frontal7.00.221.61
      Brain, left central frontal3.50.100.73
      Brain, right nuclear2.50.211.55
      Skull, left occipital theca4.00.987.24
      Pelvis8.01.4610.77
      Lung34.10.181.34
      4Brain, left cerebellar2.51.378.15
      Liver40.91.015.98
      5Brain, posterior frontal1.80.452.65
      6Brain, left frontal operculum5.80.211.25
      Brain, left posterior frontal3.20.191.12
      Brain, right frontal coronal2.50.231.38
      Vertebra10.00.694.11

    Additional Files

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      Files in this Data Supplement:

      • Supplementary Table 1 - PDF file - 70K, 124I-dosimetry data to healthy organs.
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    Cancer Immunology Research: 1 (2)
    August 2013
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    Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study
    Gian Luca Poli, Claudia Bianchi, Giorgio Virotta, Anna Bettini, Renzo Moretti, Eveline Trachsel, Giuliano Elia, Leonardo Giovannoni, Dario Neri and Andrea Bruno
    Cancer Immunol Res August 1 2013 (1) (2) 134-143; DOI: 10.1158/2326-6066.CIR-13-0007

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    Radretumab Radioimmunotherapy in Patients with Brain Metastasis: A 124I-L19SIP Dosimetric PET Study
    Gian Luca Poli, Claudia Bianchi, Giorgio Virotta, Anna Bettini, Renzo Moretti, Eveline Trachsel, Giuliano Elia, Leonardo Giovannoni, Dario Neri and Andrea Bruno
    Cancer Immunol Res August 1 2013 (1) (2) 134-143; DOI: 10.1158/2326-6066.CIR-13-0007
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