Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques.
OBJECTIVE
The use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. To facilitate clinical testing, we evaluated cetuximab conjugated to IRDye700DX (IR700) in cynomolgus macaques.


METHODS
Total IR700 and intact cetuximab-IR700 were measured in 51 tissues at 2 and 14 days after intravenous injection of 40 and 80 mg/kg cetuximab-IR700, respectively, and compared with an unlabeled cetuximab-dosed control group (two each per sex per time point per group).


RESULTS
The IR700 retrieved from all tissues at 2 and 14 days after dosing was estimated at 34.9 ± 1.8 and 2.53 ± 0.67% of the total dose, respectively. The tissues with the highest levels of intact cetuximab-IR700 at 2 days after dosing were the blood, lung, and skin. Formalin-fixed paraffin-embedded tissue sections at 2 days after dosing showed the highest IR700 signals in the axillary lymph node, mammary gland, and gall bladder.


CONCLUSIONS
Both IR700 and intact cetuximab-IR700 biodistributions were consistent with known epidermal growth factor receptor (EGFR) expression, and changes between 2 and 14 days were consistent with rapid metabolism and excretion of the cetuximab-IR700.
Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.|Department of Surgery, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.
E
E
de Boer
Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35294, USA.
S
S
Samuel
Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35294, USA.
D N
DN
French
Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
J M
JM
Warram
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
T R
TR
Schoeb
Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA, USA.
E L
EL
Rosenthal
Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35294, USA. kurtzinn@uab.edu.
K R
KR
Zinn
D000818:Animals; D000068818:Cetuximab / Q000008:administration & dosage* / Q000378:metabolism*; D004396:Coloring Agents / Q000378:metabolism*; D005260:Female; D005453:Fluorescence; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D014018:Tissue Distribution
D004396:Coloring Agents; D000068818:Cetuximab
Biodistribution; Cetuximab; IRDye700DX; Macaques; Photoimmunotherapy