Pharmacokinetics of radioimmunotherapeutic agent of direct labeling mAb ~(188)Re-HAb18

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:xumingxingHUANG
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AIM:To labed Anti-hepatoma monoclonal antibody(mAb)fragment HAb18 F(ab’)_2 was labeled with 188 Re for thepharmacokinetic model of ~(188)Re-HAb18 F(ab’)_2 and toevaluate its pharmacokinetic parameters in hepatoma-bearing nude mice.METHODS:HAb18 F(ab’)_2 was directly labeled with ~(188)Reusing 2-mercaptoethanol(2-ME)as reducing agents.Labeling efficiency and immunoreactivity of ~(188)Re-HAb18 F(ab’)_2 were evaluated by Whatman 3MM paperchromatography and live cell assay,respectively.Biodistribution analysis was also conducted in nude micebearing human hepatoma in which animals were sacrificed atdifferent time points(1,4,18,24 and 24h)after ~(188)Re-HAb18F(ab’)_2 was injected through tail-vein into hepatoma-bearingnude mice.The blood and radioactivity of organs and masswere measured.The concentrations of ~(188)Re-HAb18 F(ab’)_2were evaluated with a pharrnacokinetic 3P97 software.RESULTS:The optimum labeling efficiency andimmunoreactive fraction were 91.7% and 0.78%,respectively.The parameters of ~(188)Re-HAb18 F(ab’)_2 were:T_(1/2),2.29h;Vd,1.49×10~(-9)L·Bq~(-1);AUC,20.49×10~9Bq·h·L~(-1);CL,0.45×10~(-3)L·h~(-1).~(188)Re-HAb18 F(ab’)_2 could locatespecially in hepatoma with high selective reactivity of HAb18F(ab’)_2.~(188)Re-HAbl8 F(ab’)_2 was mainly eliminated bykidney.The maximal tumor to blood ratio was at 48h,andmaximal tumor to liver ratio was at 18h.CONCLUTION:The pharmacokinetics of ~(188)Re-HAb18 F(ab’)_2fit a I-compartment model.~(188)Re-HAb18 F(ab’)_2 can beuptaken selectively at the hepatoma site. AIM: To labed Anti-hepatoma monoclonal antibody (mAb) fragment HAb18 F (ab ’) _ 2 was labeled with 188 Re for the pharmacokinetic model of ~ 188 Re-HAb 18 F (ab’) _ 2 and to evaluate its pharmacokinetic parameters in hepatoma- bearing nude mice. METHHODS: HAb18 F (ab ’) _ 2 was directly labeled with ~ (188) Reusing 2-mercaptoethanol ) _2 were evaluated by Whatman 3MM paperchromatography and live cell assay, respectively. Biodistribution analysis was also conducted in nude micebearing human hepatoma in which the animals were sacrificed at different time points (1,4,18,24 and 24h) after ~ (188) Re -HAb18F (ab ’) _ 2 was injected through tail-vein into hepatoma-bearing nude mice. The blood and radioactivity of organs and masswere measured. These concentrations of ~ (188) Re-HAb18 F (ab’) _2were evaluated with a pharrnacokinetic 3P97 software.RESULTS: The optimum labeling efficiency and immunoreactive fraction were 91.7% and 0.78% respectively.The param (188) Re-HAb18 F (ab ’) _ 2 were: T 1/2 (1/2), 2.29 h; Vd, 1.49 × 10 -9 L · Bq -1; AUC, 20.49 × 10 ~ 9Bq · h · L -1; CL, 0.45 × 10 -3 L · h -1. (188) Re-HAb18 F (ab ’) _2 could locatespecially in hepatoma with High selective reactivity of HAb18F (ab ’) _2.- (188) Re-HAbl8 F (ab’) _ 2 was mainly eliminated by kidney.The maximal tumor to blood ratio was at 48h, and maximal tumor to liver ratio was at 18h.CONCLUTION: The pharmacokinetics of ~ (188) Re-HAb18 F (ab ’) _2fit a I-compartment model. ~ (188) Re-HAb18 F (ab’) _2 can be betaken selectively at the hepatoma site.
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