TY - JOUR
T1 - Radiation dosimetry of
89
Zr-labeled chimeric monoclonal antibody U36 as used for immuno-PET in head and neck cancer patients
AU - Börjesson, Pontus K.E.
AU - Jauw, Yvonne W.S.
AU - De Bree, Remco
AU - Roos, Jan C.
AU - Castelijns, Jonas A.
AU - Leemans, C. René
AU - Van Dongen, Guus A.M.S.
AU - Boellaard, Ronald
PY - 2009/11/1
Y1 - 2009/11/1
N2 -
Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter
89
Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans
89
Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the
89
Zr- labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. Methods: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of
89
Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo radioactivity measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. Results:
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Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% ± 16.9% [mean ± SD]) except for heavy-weight patients (>100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, 28.4% ± 34.5%). The mean absorbed red marrow dose was 0.07 ± 0.02 mSv/MBq and 0.09 ± 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 ± 0.27 mSv/MBq in men and 1.35 ± 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 ± 0.03 mSv/MBq in men and 0.66 ± 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. Conclusion:
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Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAb-based therapy.
AB -
Immuno-PET is an appealing concept in the detection of tumors and planning of antibody-based therapy. For this purpose, the long-lived positron emitter
89
Zr (half-life, 78.4 h) recently became available. The aim of the present first-in-humans
89
Zr immuno-PET study was to assess safety, biodistribution, radiation dose, and quantification of the
89
Zr- labeled chimeric monoclonal antibody (cmAb) U36 in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the performance of immuno-PET for detecting lymph node metastases was evaluated, as described previously. Methods: Twenty HNSCC patients, scheduled to undergo surgical tumor resection, received 75 MBq of
89
Zr-cmAb U36 (10 mg). Immuno-PET scans were acquired at 1, 24, 72, or 144 h after injection. The biodistribution of the radioimmunoconjugate was evaluated by ex vivo radioactivity measurement in blood and in biopsies from the surgical specimen obtained at 168 h after injection. Uptake levels and residence times in blood, tumors, and organs of interest were derived from quantitative immuno-PET studies, and absorbed doses were calculated using OLINDA/EXM 1.0. The red marrow dose was calculated using the residence time for blood. Results:
89
Zr-cmAb U36 was well tolerated by all subjects. PET quantification of blood-pool activity in the left ventricle of the heart showed a good agreement with sampled blood activity (difference equals 0.2% ± 16.9% [mean ± SD]) except for heavy-weight patients (>100 kg). A good agreement was also found for the assessment of mAb uptake in primary tumors (mean deviation, 28.4% ± 34.5%). The mean absorbed red marrow dose was 0.07 ± 0.02 mSv/MBq and 0.09 ± 0.01 mSv/MBq in men and women, respectively. The normal organ with the highest absorbed dose was the liver (mean dose, 1.25 ± 0.27 mSv/MBq in men and 1.35 ± 0.21 mSv/MBq in women), thereafter followed by kidneys, thyroid, lungs, and spleen. The mean effective dose was 0.53 ± 0.03 mSv/MBq in men and 0.66 ± 0.03 mSv/MBq in women. Measured excretion via the urinary tract was less than 3% during the first 72 h. Conclusion:
89
Zr immuno-PET can be safely used to quantitatively assess biodistribution, uptake, organ residence times, and radiation dose, justifying its further clinical exploitation in the detection of tumors and planning of mAb-based therapy.
KW - Zr-labeled monoclonal antibody
KW - Dosimetry
KW - Head and neck cancer patients
KW - Immuno-PET
KW - Molecular imaging
UR - http://www.scopus.com/inward/record.url?scp=70350736124&partnerID=8YFLogxK
U2 - 10.2967/jnumed.109.065862
DO - 10.2967/jnumed.109.065862
M3 - Article
C2 - 19837762
AN - SCOPUS:70350736124
SN - 0161-5505
VL - 50
SP - 1828
EP - 1836
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 11
ER -