Radiation dosimetry of 89Zr-labeled chimeric monoclonal antibody U36 as used for immuno-PET in head and neck cancer patients.
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, -8.4% +/- 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.


CONCLUSIONS
(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.
Börjesson
Pontus K E
PK
Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Jauw
Yvonne W S
YW
de Bree
Remco
R
Roos
Jan C
JC
Castelijns
Jonas A
JA
Leemans
C René
CR
van Dongen
Guus A M S
GA
Boellaard
Ronald
R
D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D001853:Bone Marrow / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism; D002986:Clinical Trials as Topic; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D011868:Radioisotopes; D011874:Radiometry; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015040:Zirconium / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D011993:Recombinant Fusion Proteins; D015040:Zirconium