(125)I-labeled anti-bFGF monoclonal antibody inhibits growth of hepatocellular carcinoma.
OBJECTIVE
To investigate the inhibitory efficacy of (125)I-labeled anti-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in hepatocellular carcinoma (HCC).


METHODS
bFGF mAb was prepared by using the 1G9B9 hybridoma cell line with hybridization technology and extracted from ascites fluid through a Protein G Sepharose affinity column. After labeling with (125)I through the chloramine-T method, bFGF mAb was further purified by a Sephadex G-25 column. Gamma radiation counter GC-1200 detected radioactivity of (125)I-bFGF mAb. The murine H22 HCC xenograft model was established and randomized to interventions with control (phosphate-buffered saline), (125)I-bFGF mAb, (125)I plus bFGF mAb, bFGF mAb, or (125)I. The ratios of tumor inhibition were then calculated. Expression of bFGF, fibroblast growth factor receptor (FGFR), platelet-derived growth factor, and vascular endothelial growth factor (VEGF) mRNA was determined by quantitative reverse transcriptase real-time polymerase chain reaction.


RESULTS
The purified bFGF mAb solution was 8.145 mg/mL with a titer of 1:2560000 and was stored at -20 °C. After coupling, (125)I-bFGF mAb was used at a 1: 1280000 dilution, stored at 4 °C, and its specific radioactivity was 37 MBq/mg. The corresponding tumor weight in the control, (125)I, bFGF mAb, (125)I plus bFGF mAb, and (125)I-bFGF mAb groups was 1.88 ± 0.25, 1.625 ± 0.21, 1.5 ± 0.18, 1.41 ± 0.16, and 0.98 ± 0.11 g, respectively. The tumor inhibition ratio in the (125)I, bFGF mAb, (125)I plus bFGF mAb, and (125)I-bFGF mAb groups was 13.6%, 20.2%, 25.1%, and 47.9%, respectively. Growth of HCC xenografts was inhibited significantly more in the (125)I-bFGF mAb group than in the other groups (P < 0.05). Expression of bFGF and FGFR mRNA in the (125)I-bFGF mAb group was significantly decreased in comparison with other groups (P < 0.05). Groups under interventions revealed increased expression of VEGF mRNA (except for (125)I group) compared with the control group.


CONCLUSIONS
(125)I-bFGF mAb inhibits growth of HCC xenografts. The coupling effect of (125)I-bFGF mAb is more effective than the concomitant use of (125)I and bFGF mAb.
Peng-Hui Hu, Lan-Hong Pan, Wen-Hui Chen, Meng Xu, Department of Oncology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China.
Peng-Hui
PH
Hu
Peng-Hui Hu, Lan-Hong Pan, Wen-Hui Chen, Meng Xu, Department of Oncology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China.
Lan-Hong
LH
Pan
Peng-Hui Hu, Lan-Hong Pan, Wen-Hui Chen, Meng Xu, Department of Oncology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China.
Patrick Ting-Yat
PT
Wong
Peng-Hui Hu, Lan-Hong Pan, Wen-Hui Chen, Meng Xu, Department of Oncology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China.
Wen-Hui
WH
Chen
Peng-Hui Hu, Lan-Hong Pan, Wen-Hui Chen, Meng Xu, Department of Oncology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China.
Yan-Qing
YQ
Yang
Peng-Hui Hu, Lan-Hong Pan, Wen-Hui Chen, Meng Xu, Department of Oncology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China.
Hong
H
Wang
Peng-Hui Hu, Lan-Hong Pan, Wen-Hui Chen, Meng Xu, Department of Oncology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China.
Jun-Jian
JJ
Xiang
Peng-Hui Hu, Lan-Hong Pan, Wen-Hui Chen, Meng Xu, Department of Oncology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China.
Meng
M
Xu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects*; D016222:Fibroblast Growth Factor 2 / Q000276:immunology* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006825:Hybridomas; D007457:Iodine Radioisotopes / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D040262:Receptors, Vascular Endothelial Growth Factor
125Iodine; Basic fibroblast growth factor; Fibroblast growth factor receptor; Hepatocellular carcinoma; Monoclonal antibody; Vascular endothelial growth factor