Clinical observation of 125 I labeled anti alpha fetoprotein antibody radioimmunotherapy in hepatocellular carcinoma *

AIM To observe the therapeutic effects and toxic side reactions of 125 I labeled hourse anti human AFP polyclonal antibodies in immuno targeting therapy against hepatocellular carcinoma (HCC).

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

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-HAb18 F(ab')_2 and to evaluate its pharmacokinetic parameters in hepatoma- bearing nude mice. METHODS:HAb18 F(ab')_2 was directly labeled with ^(188)Re using 2-mercaptoethanol(2-ME)as reducing agents. Labeling efficiency and immunoreactivity of ^(188)Re-HAb18 F (ab')_2 were evaluated by Whatman 3MM paper chromatography and live cell assay,respectively. Biodistribution analysis was also conducted in nude mice bearing human hepatoma in which animals were sacrificed at different time points(1,4,18,24 and 24h)after ^(188)Re-HAb18 F(ab')_2 was injected through tail-vein into hepatoma-bearing nude mice.The blood and radioactivity of organs and mass were measured.The concentrations of ^(188)Re-HAb18 F(ab')_2 were evaluated with a pharrnacokinetic 3P97 software. RESULTS:The optimum labeling efficiency and immunoreactive 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 locate specially in hepatoma with high selective reactivity of HAb18 F(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')_2 fit a I-compartment model.^(188)Re-HAb18 F(ab')_2 can be uptaken selectively at the hepatoma site.

Avidin-biotin system pretargeting radioimmunoimaging and radioimmunotherapy and its application in mouse model of human colon carcinoma

AIM： To evaluate the multi-step pretargeting radioimmunoimaging （RII） and radioimmunotherapy （RTT） in nude mice bearing human colon carcinoma with avidin-biotin system labeled with 153^Sm. METHODS： Two- and three-step strategies for avidinbiotin system pretargeting techniques were established. In a three-step procedure, human colon carcinoma bearing nude mice were first injected with biotinylated monoclonal antibody （McAb-Bt） followed by cold avidin （Av） 48 h later and then 153^Sm-DB2 24 h thereafter; whereas the twostep procedure consisted of injection of 153^Sm-SA 48 h after pretargeting with biotinylated anti-CEA monoclonal antibody （CEA McAb-Bt）. SPECT imaging and biodistribution were performed at 4, 24, 48, or 72 h after injection of 153^Sm-labeled compounds. Five groups of nude mice subcutaneously grafted with human colon carcinoma were treated 3 d after grafting. One group received the injection with 100 μg CEA McAb-Bt followed by cold avidin （80 μg） after 2 d and 11.1 MBCl I53Sm-DB2 after 1 d. Four control groups were treated respectively with 11.1 MBq 153^Sm- CEA McAb, ii.i MBq 153^Sm-nmIgG, ii.i MBq 153^Sm-DB2, 100 μL normal saline. Toxicity was evaluated by changes of leukocyte count, and the efficacy by variation in tumor volume. Histological analyses of tumors were performed. RESULTS： The three-step procedure allowed faster blood clearance and yielded higher tumor blood ratios （5.76 at 4 h and 12.94 at 24 h） of the 153^Sm-DB2. The tumor was clearly visualized at 4 h in y-imaging after the injection of 153^Sm-DB2, while a significant accumulation of 153^Sm-SA in the tumor was observed only 24 h after the injection and tumor blood ratios at 4 and 24 h were 1.00 and 2.03, respectively, in the two-step procedure. Pretargeting RIT and 153^Sm-CEA McAb had a strong tumor-inhibiting effect.The tumor inhibitory rate was 80.67% and 78.44%, respectively, five weeks after therapy. Histopathological evidence also indicated radioactive damage in tumor tissues as necrosis of tumor cells, while in the other organs such as liver and kidney no radioactive damage was observed. Leukocyte counts showed significant decrease after treatment in groups of 153^Sm-CEA McAb and 153^Sm- nmIgG. CONCLUSION： The two kinds of pretargeting strategies can elevate the target-to-nontarget ratio, decrease the blood background and shorten the imaging time compared to 153^Sm-CEA McAb. Three-step pretargeting RIT is as effident as 153^Sm-CEA McAb, but markedly less toxic. This study provides experimental evidence for the clinical application of pretargeting RII and RIT.

Enhanced radioimmunotherapeutic efficacy of a monoclonal antibody cocktail against SMMC-7721 human hepatocellular carcinoma

The improved tumoricidal effect of the radioatibody mixture ("cocktail") has been reported recently for the treatment of colon tumor. In the present study, we demonstrated the enhanced radioimmunotherapeutic efficacy of a monoclonal atibody (MAb) cocktail against human hepatocellular carcinoma. Therapeutic efficacy was determined by measuring the change in tumor size over a period, determining the percentage of growth inhibition of each treatment at various times after radioantibody therapy. boioimmunotherapy of SMMC-7721 human hepatoma xenografts in athymic nude mice with combination of 131I labeled Hepama-1 and 131Llabeled 9403 mouse MAbs was more effective than using either Hepeam-1 or 9403 Mab alone The MAb cocktail could target a greater number of hepstoma cells and increase the magnitude of hepatoma cen uptde of radioamibodies. The in vjtro results explain the enhanced effect of the MAb cocktail in in vjvo model system.

Enhancement of CD4^+ T cell activities and modulation of Th1/Th2 lineage development in radiated tumor-bearing rats treated with male zooid of Antheraea pernyi extracts

AIM： To investigate whether supplementation of male zooid of Antheraea pernyi extracts （MZAPE） could enhance immune function of radiated tumor-bearing rats. METHODS： Eighty male Wistar rats were randomly divided into a control group, a simple radiation group, a MZAPE group, and a radiation plus MZAPE group. With the tumor model established by implanting Walker-256 ascites tumor cells, tumor weight and tumor control rate were calculated. The rats in the simple radiation and radiation plus MZAPE groups were underwent to radiation at 10 Gy within 2 d. In the MZAPE and radiation plus MZAPE groups, the MZAPE was gavaged at a dose of 16.53 mg/kg once a day for 7 d. T cell subsets in peripheral blood were determined by flow cytometry and the expression of IL-2, IFN-γ, IL-4 and IL-10 in sera were determined by ELISA on the 8th d. RESULTS： The tumor weight of simple radiation group, MZAPE group and radiation plus MZAPE group was lower than that of control group （P 〈 0.01） and tumor control rates were 63.08% ± 6.43%, 69.86%± 7.12% and 35.30% ± 7.67%, respectively. CD^4＋ T and CD^8＋ T cells in the peripheral blood of the simple radiation group were fewer than in control group. In the MZAPE and radiation plus MZAPE groups, the number of CD^4＋ T cells was higher while CD^8＋ T cells was lower than in the control and simple radiation groups. Expression of IL-2 and INF-y in the radiation group was lower than in control group, and significantly enhanced during MZAPE therapy （P 〈 0.05）. Expression of IL-4 and IL-10 in the radiation group had no significant changes compared with the control group, and decreased significantly after MZAPE treatment （P 〈 0.01）. CONCLUSION： MZAPE administration may help improve the immune function of the radiated tumor-bearing rats and reverse the radiation-induced immune inhibition by promoting the proliferation of T helper cells and inducing the transdifferentiation from Th2 to Th1.