Experimental And Clinical Study On The Treament Of Hepatic Cancer With Internal Radiation Therapy

PART 1: Experimental study on the treatment of hepatic cancer by intratumoral injection of MAA and colloidal ³²PObjectiveTo investigate the tumor deposition, systemic biodistribution and the therapeutic effect of colloidal ³²P in different intratumoral injection methods.Methods1.H₂₂ hepatocellular cancer cells were inoculated subcutaneously in 60 male B alb/c mice, which were individed into four equal groups randomly when the tumor reached 1.0cm in diameter.2.1.85MBq/0.1ml of colloidal ³²P were injected slowly into tumors in one group. 1×10⁴ particles of MAA/0.1ml followed by 1.85MBq/0.1ml of colloidal ³²P were injected in another group, 1×10⁵ articles of MAA/0.1ml followed by 1.85MBq/0. 1ml of colloidal ³²P were injected in the third group, and 1×10⁵ particles of MAA /0.1ml followed by 1.85MBq/0.25ml of colloidal ³²P were injected in the forth.3. Three mice from each group were sacrificed at 30min, 24h, 48h, 8d and 16d postinjection. A sample of 100ul blood was acquired. Bremsstrahlung imaging was performed in mice of the forth group. 4. The whole tumor, heart, liver, spleen, kidney, lung and bone of each animal were removed, weighted, and counted for radioactivity in a gamma counter.Results1 .The diffusion of colloidal ³²P from tumor to blood occurred mainly in the early stage after injection of MAA particles number led to a better retention of colloidal ³²P in tumors, but when the number of MAA particles were same, the obstructive effectiveness decreased with increased doses of colloidal ³²P.2.For tumors with a diameter of 1.0cm, a dose of 18.5MBq colloidal ³²P was found to control the tumor growth with no bone marrow suppression.ConclusionsIt is a safe and effective therapy for unresectable hepatic cancer to inject intratumorally a certain, number of MAA particles followed by a proper dose of colloidal ³²P.PART 2: Ultrasound-Guided intratumoral MAA and P-32 chromic phosphate injection therapy for patients with hepatic cancerObjectiveTo investigate the treatment potential of an intratumoral infusional brachytherapy using macroaggregated human albumin in combination with radioactive chromic phosphate ³²P in this group of hepatic patients.MethodsThirty-two patients with unresectable hepatic cancer received intratumoral infusional brachytherapy. Treatment and assessment of responses were performed with the aid of ultrasonography. The clinical responses and toxic effects were analyzed on basis of clinical symptoms and laboratory data, including the tumor size, histopathological changes, AFP estimation, blood routine, hepatic and renal functions and immunocompetence assays before and after treatment.Results 1 .Alleviation of symptoms, decreased AFP levels, fibrosis and complete or partial necrosis within tumor lesions were observed afterintratumoral injection with MAA and ³²P.2.Five (15.6%) patients had complete response ,20/32(62.5%) patients had partial response, 6/32(18.8%) patients had stable disease and 1/32(3.1%) patients had progression disease, corresponding to an objective response of 78.1%. Hepatic lesions became resectable in 8 patients for whom successful operation was performed. The 1-, 2- and 3-year survival rates were 90.6%, 71.9% and 40.6%, respectively. The median survival period was 16months.3.No evidence of non-sealed radionuclide-induced toxic reactions or complications were observed.ConclusionsIntratumoral infusional brachytherapy using radioactive colloidal chromic phosphate has the potential to reduce inoperable hepatic carcinoma with few side effects.PART 3: Intratumoral injection of ¹⁵³Sm-RMS into an animal model of hepatomaObjectiveTo investigate the tumor deposition and systemic biodistribution of ¹⁵³Sm-microspheres after intratumoral injection.To evaluate the efficacy of treatment for hepatoma in mice.Methods1.H₂₂ hepatocellular carcinoma cells was inoculated subcuta-neously in the right thorax of Balb/c mice.2. After 10 days, 66 mice bore tumor with 1cm of diameter were divided into four groups randomly. The mice of the first group that included 48 mice were used to determine the biodistribution of ¹⁵³Sm-RMS after intratumoral injection 18.5 MBq/0.1ml on each mouse. The second and third groups that comprised 6 mice respectively were used to evaluate the efficacy of treatment. Group 2 received intratumoral injection of 370MBq/0.1ml ^l53Sm-RMS and group 3 received 555MBq/0.15ml. Six mice were served as the control group (group 4) without any treatment.3. Four mice of the first group were sacrificed at 30min, 1.5h, 2h, 4h, 8h, 24h, 2d, 3d, 4d, 6d, 8d and 10d after the injection. A sample of 1ml blood was obtained. The whole tumor, heart, liver, spleen, kidney, lung and the sample of bone and muscle were taken, weighted, counted for radioactivity in a gamma counter and then calculated the tissue concentrations which expressed as percentage injected dose per gram (% ID/g). In addition the tumor size of group 2 and 3 were measured to calculate the contraction ratio and under anesthesia imaged using Gamma camera at 4d, 8d, 12d, 16d and 20d.postinjection.4. At 2d, 12d and 20d, two mice were killed and tumors were removed to make pathological tissue slice in addition to acquire the samples of blood to count erythrocyte, leukocyte and blood platelet.Results1. After intratumoral injection,¹⁵³Sm-RMS were essentially accumulated in the tumor with deposition dose of 94.34% in 30min and 62.21% at 8d.2. A few ^l53Sm-RMS diffused from the tumor and were mianly found in the lung and liver.But it declined rapidly over time with no harm to them.3. It showed that the tumor size of the group 2 and 3 decreased significantly at 8d postinjection. The tumor contraction ratio declined a little after 8 days, which maybe caused by the limited injection dose. In both groups, the response was obvious and the group 3 was better than group 2. Pathological result showed most tumor-cells were killed. In addition, no bone marrow suppression occurred.ConclusionsAs ¹⁵³Sm-RMS have a stable labeling ability and essentially deposited in the tumor after intratumoral injection, it appears to be a novel ideal radiopharmaceutical for interstitial intervention therapy.