TY - JOUR
T1 - Phase 0 microdosing PET study using the human mini antibody F16SIP in head and neck cancer patients
AU - Heuveling, Derrek A.
AU - De Bree, Remco
AU - Vugts, Danielle J.
AU - Huisman, Marc C.
AU - Giovannoni, Leonardo
AU - Hoekstra, Otto S.
AU - Leemans, C. René
AU - Neri, Dario
AU - Van Dongen, Guus A.M.S.
PY - 2013/3/1
Y1 - 2013/3/1
N2 - The aim of this microdosing phase 0 clinical study was to obtain initial information about pharmacokinetics, biodistribution, and specific tumor targeting of the antitenascin-C mini antibody F16SIP. Methods: Two milligrams of F16SIP, labeled with 74 MBq of 124I, were intravenously administered to patients with head and neck cancer (n 5 4) scheduled for surgery 5-7 d later. Immuno-PET scans were acquired at 30 min and 24 h after injection. For pharmacokinetic analysis, blood samples were taken at different time points after infusion. Tissue uptake was extracted from whole-body PET scans. In addition, ex vivo radioactivity measurements of blood and of biopsies from the surgical specimens were performed. Results: 124I-F16SIP was well tolerated. Uptake was visible mainly in the liver, spleen, kidneys, and bone marrow and diminished over time. Tumor uptake increased over time, with all 4 tumors visible on 24-h PET images. The tumor-to-blood ratio was 7.7 ± 1.7 at the time of surgery. Pharmacokinetic analysis revealed good bioavailability of 124I-F16SIP. Conclusion: Performing a microdosing immuno-PET study appeared feasible and demonstrated adequate bioavailability and selective tumor targeting of 124I-F16SIP.The results of this study justify further clinical exploration of 124I-F16SIP-based therapies. COPYRIGHT
AB - The aim of this microdosing phase 0 clinical study was to obtain initial information about pharmacokinetics, biodistribution, and specific tumor targeting of the antitenascin-C mini antibody F16SIP. Methods: Two milligrams of F16SIP, labeled with 74 MBq of 124I, were intravenously administered to patients with head and neck cancer (n 5 4) scheduled for surgery 5-7 d later. Immuno-PET scans were acquired at 30 min and 24 h after injection. For pharmacokinetic analysis, blood samples were taken at different time points after infusion. Tissue uptake was extracted from whole-body PET scans. In addition, ex vivo radioactivity measurements of blood and of biopsies from the surgical specimens were performed. Results: 124I-F16SIP was well tolerated. Uptake was visible mainly in the liver, spleen, kidneys, and bone marrow and diminished over time. Tumor uptake increased over time, with all 4 tumors visible on 24-h PET images. The tumor-to-blood ratio was 7.7 ± 1.7 at the time of surgery. Pharmacokinetic analysis revealed good bioavailability of 124I-F16SIP. Conclusion: Performing a microdosing immuno-PET study appeared feasible and demonstrated adequate bioavailability and selective tumor targeting of 124I-F16SIP.The results of this study justify further clinical exploration of 124I-F16SIP-based therapies. COPYRIGHT
KW - Head and neck cancer
KW - Immuno-PET
KW - Microdosing
KW - Monoclonal antibody
KW - Phase 0
UR - https://www.scopus.com/pages/publications/84874857624
U2 - 10.2967/jnumed.112.111310
DO - 10.2967/jnumed.112.111310
M3 - Article
C2 - 23334725
AN - SCOPUS:84874857624
SN - 0161-5505
VL - 54
SP - 397
EP - 401
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 3
ER -