131I-recombinant human EGF has antitumor effects against MCF-7 human breast cancer xenografts with low levels of EGFR.
This study investigated the inhibitory action of (131)I-recombinant human EGF ((131)I-rhEGF) on MCF-7 human breast cancer tumor development in nude mice. The activity and tumor uptake of (131)I-rhEGF was measured by tissue distribution assay, and its effect on tumor growth was measured by monitoring tumor size after treatment with (131)I-rhEGF. Changes in tumor cell ultrastructure were observed by transmission electron microscopy (TEM), and pathological changes in tumor tissue were observed by light microscopy. The tissue distribution assay revealed that (131)I-rhEGF was markedly absorbed by the tumor and reached its maximal uptake rate (16.73%ID. g(-1)) at 120 hours at which point the drug concentration in the tumor was 11.1-fold, 8.1-fold, and 6.6-fold higher than that in blood, liver, and kidneys, respectively. Tumor size measurements showed that tumor development was significantly inhibited by intravenously and intratumorally injected (131)I-rhEGF. Tumor inhibition rates (82.0% and 80.7%, respectively) were significantly higher than those of tumors treated with (131)I (7.49%) and (131)I-HSA (6.91%; P < 0.05). TEM and light microscopy revealed that intravenous and intratumoral injection of (131)I-rhEGF could significantly damage and ultimately kill tumor cells. Our results suggest that (131)I-rhEGF suppresses development of xenografted breast cancer cells in nude mice, providing a novel candidate for receptor-mediated targeted radiotherapy.
Li
Yun Chun
YC
Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu 610041, China. ycliwc@163.com
Xu
Wei Yun
WY
Tan
Tian Zhi
TZ
He
Sheng
S
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D002455:Cell Division / Q000528:radiation effects; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics*; D066246:ErbB Receptors / Q000172:deficiency*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009367:Neoplasm Staging; D009928:Organ Specificity; D016499:Radioimmunotherapy / Q000379:methods; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D016896:Treatment Outcome
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors