Unusual Adrenal and Brain Metastases From Follicular Thyroid Carcinoma Revealed by 131I SPECT/CT.

The adrenal metastasis from differentiated thyroid carcinoma is uncommon. Metastatic involvement of both adrenal and brain in the same patient from differentiated thyroid carcinoma is rare. Here, we described an unusual case with iodine-avid lung, bone, adrenal, liver, and brain metastases from follicular thyroid carcinoma confirmed by 131I SPECT/CT. The utilization of SPECT/CT in thyroid cancer patients can detect the presence of metastases and also exclude potential false-positive lesions. Our case demonstrates that SPECT/CT is helpful in localizing and confirming metastatic lesions from differentiated thyroid carcinoma in rare and unusual sites.

Comparison of presentation and clinical outcome between children and young adults with differentiated thyroid cancer.

BACKGROUND: The aim of the present study was to evaluate the presentation, clinical course and outcome between children and young adults with differentiated thyroid cancer (DTC) treated in our hospital. MATERIALS AND METHODS: The medical records of 145 patients with DTC who underwent surgery followed by radioiodine and thyroid hormone (TSH) suppression were retrospectively reviewed. The follow up was between January 2006 and June 2012. These patients consisted of 38 children (age ≤ 18 y) and 107 young adult patients (age ≤ 30 y). The clinical characteristics and outcome were analyzed and compared, and the progression-free survival (PFS) was evaluated using the Kaplan-Meier method. RESULTS: At initial diagnosis, a greater degree of extra thyroidal extension was found in children than adults patients (p<0.001). However, there was no significant difference between the two groups with regard to the tumor size and the presence of lymph node or distant metastasis (p=0.172, p=0.050 and p=0.068, respectively). The extent of surgery and the cumulative or mean dose of radioiodine were similar in both groups. During the follow up, the overall survival rate was 100% for both groups, and the PFS rate was similar in children and in young adults group (log rank test, χ2=0.126, p=0.723). CONCLUSIONS: In comparison to the young adult patients, DTC in children presents with more aggressive behavior, but outcomes are similar between the two groups after the intensive management of surgery followed by radioiodine and TSH suppression therapy.

131I-labeled metuximab combined with chemoembolization for unresectable hepatocellular carcinoma.

AIM: To investigate the safety and effectiveness of combined (131)I-metuximab and transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS: One hundred and eighty-five patients (159 men and 26 women) with advanced HCC were enrolled in this study from February 2009 to July 2011. There were 95 patients in the combined metuximab and TACE group, and 90 patients in the TACE only group. The patients were followed for 12 mo. Clinical symptoms, blood cell counts, Karnofsky Performance Score (KPS) evaluation and therapeutic effects according to the Response Evaluation Criteria in Solid Tumors were recorded and evaluated. RESULTS: The 1-mo effective rates (complete response + partial response + stable disease) of the test group and control group were 71.23% and 38.89%, respectively (P < 0.001). The 6-, 9- and 12-mo survival rates were 86.42%, 74.07% and 60.49% for the test group and 60.0%, 42.22% and 34.44% for the control group (P < 0.001). The incidence of adverse events (gastrointestinal symptoms, fever and pain) and blood cell toxicity were significantly higher for the test group than for the control group (P < 0.001). No severe (131)I-metuximab-related complications were identified. With respect to efficacy, patients in the test group had greater improvement in tumor-related pain (P = 0.014) and increase in KPS (P < 0.001) than those in the control group. CONCLUSION: Combination of (131)I-metuximab and TACE prolonged the survival time in patients with HCC compared with TACE alone. The combination treatment was safe and effective.

Puncture injection of para-toluenesulfonamide combined with chemoembolization for advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is difficult to eradicate due to its resilient nature. Portal vein is often involved in tumors of large size, which exclude the patient from surgical resection and local ablative therapy, such as percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) because they were considered neither effective nor safe. Currently, there is almost no effective treatment for HCC of such condition. As a unique antitumor agent in form of lipophilic fluid for local injection, para-toluenesulfonamide (PTS) produces mild side effects while necrotizing the tumor tissues quickly and efficiently. Being largely different from both PEI and RFA therapies, PTS can disseminate itself in tumors more easily than other caustic agents, such as alcohol. So PTS may offer additional benefit to HCCs with vascular involvement. We herein describe a 70-year-old HCC patient who was treated with the combination of PTS injection and transcatheter arterial chemoembolization, resulting in a significantly improved clinical prognosis.

[Development of a predicting model to estimate the probability of malignancy of solitary pulmonary nodules].

OBJECTIVE: To evaluate the role of (18)F-FDG PET/CT in characterizating solitary pulmonary nodule (SPN) and bone lesions. METHODS: 105 patients with a SPN smaller than 30 mm in axial diameter were recruited for this study. PET/CT images were obtained 60 min after intravenous injection of (18)F-FDG. Logistic regression analysis was performed to identify clinical predictors of SPN malignancy including age, sex, smoking history, malignant history, family history, symptoms, size, location, CT appearances, (18)F-FDG uptake, and to develop a clinical prediction model to estimate the probability of malignancy in the patients with SPN. The model fit was evaluated and the area under curve (AUC) of receiver operating characteristic (ROC) was used to evaluate the power of the model. RESULTS: The logistic regression analysis indicated that male, a positive smoking history, older age, larger nodule diameter, nodule with specula and nodule with high (18)F-FDG uptake were more likely to have malignant SPN. The clinical prediction model is described by the following equation: Logit(P) = -8.722 + 2.448 (gender) + 2.023(smoking) + 0. 851(age) + 1.057 (diameter) + 2.432 (spiculation) + 1.502 (FDG uptake). The AUC of the model was 0.892 (95% confidence interval 0.817 - 0.941). The prediction model had high accuracy in predicting malignant SPN, with 90.2%, 84.1 % and 87.6% sensitivity, specificity and accuracy respectively when the cut off value was set at 0.67. CONCLUSION: The prediction model is valid in predicting the probability of malignant SPN.

[Pharmacokinetics and tissue distribution of long circulating liposomes in rabbits and mice].

OBJECTIVE: To investigate the pharmacokinetic profiles and tissue distribution of long circulating liposome formulations-anionic, cationic, and neutral long circulating liposomes (NA, PA, A-D) in rabbits and mice. METHODS: Conventional liposomes (CA) encapsulated with 125I-bcl-2/bcl-xl ASON and free 125I-bcl-2/bcl-xl ASON (FA) were intravenously administered to rabbits and mice. The blood samples from rabbits and organs from mice were collected, respectively. The radioactivity of the blood and tissues samples were measured. RESULTS: The clearance of the four kinds of liposomes and FA exhibited bicompartmental behaviors. Compared with others, NA demonstrated favourable pharmacokinetic properties characterized with enhancement of T9(1/2 alpha) and T(1/2 beta), increased area under concentration-time curve, and decreased liver uptake. Higher uptake in the liver, spleen and kidney of mice and lower uptake in the brain, muscle, and bone of mice were observed shortly after intravenous injection of the four different kinds of liposomes and FA. A 30% decrease in uptake of NA was found in the liver of mice four hours after intravenous injection compared with the uptake of CA. No significant differences were found in the uptake of the four kinds of liposomes in the spleen of mice (P > 0.05). CONCLUSION: NA is promising as a carrier for radio-antisense therapy.

Recognition of fibrous dysplasia of bone mimicking skeletal metastasis on 18F-FDG PET/CT imaging.

PURPOSE: Fibrous dysplasia of bone (FDB) reveals intense 18F-FDG uptake mimicking metastases on 18F-FDG PET/CT. We reviewed sites of FDB revealed by 18F-FDG PET/CT imaging to allow identification of this abnormality. MATERIALS AND METHODS: Eleven patients (7 male, 4 female, aged 16-78 years) were evaluated after 55 MBq (0.15 mCi)/kg 18F-FDG utilizing a 16-slice multiple detector CT (MDCT) whole-body PET scanner, with LOR algorithm 3D reconstruction. One- and 2-h imaging was performed in 9 patients. Standard uptake value (SUV) for each lesion, on early and delayed imaging, was calculated. Lesions were confirmed in 6 patients by biopsy. The PET images correlated with MDCT to establish the imaging characteristics. RESULTS: Solitary lesions were found in 4 patients, two lesions in 1 patient, and in 6 patients there were multiple bone lesions. The SUV(early) ranged from 1.23 to 9.64 with an average of 3.76 ± 2.40. The SUV(delayed) ranged from 1.76 to 11.42 with an average of 4.51 ± 3.07. The SUV(delayed) decreased or increased slightly (-31% to 5%) in 6 of our patients, and increased significantly (11% to 39%) in 3. There was a negative correlation between SUVs and age, as well as the number of affected bones. CONCLUSIONS: In our study, FDB had wide skeletal distribution with variability of 18F-FDG uptake and CT appearance. SUV in the delayed stage was seen to either decrease or increase on dual-time 18F-FDG PET scanning. It is very important to recognize the characteristics of this skeletal dysplasia to allow differentiation from skeletal metastasis.

[Determining the activities of 131I with dose-rate constraint method for the treatment of differentiated thyroid carcinoma with diffuse pulmonary metastases].

OBJECTIVE: To compare the dose-rate constraint method with empiric fixed activity method in determining the activities of 131I for the treatment differentiated thyroid carcinoma (DTC) with diffuse pulmonary metastases. METHODS: The 80 mCi rule, a rule developed by the Medical Internal Radiation Dosimetry (MIRD) formalism, which states that the whole body retention of 131I at 48 h should not exceed 2.96 GBq (80 mCi), was applied to calculate the dose-rate constraint to lungs at 48 h in 131I therapy of DTC with diffuse pulmonary metastases. Ten consecutive DTC patients with diffuse pulmonary metastases were prospectively recruited. The whole body planar scintigrams were obtained after administration of 7.4 GBq 111I to the patients to acquire the kinetic parameters. According to the dose-rate constraint to lungs at 48 h, the activities of 131I were determined individually. RESULTS: According to the 80 mCi rule and MIRD formalism, the absorbed dose-rate to lungs at 48 h should not exceed 46.4 mGy/h in 131I therapy of DTC with diffuse pulmonary metastases. The activities of nine patients determined by the dose-rate constraint method were larger than 7.4 GBq. CONCLUSION: Dose-rate constraint method can reasonably adjust the activities of 131I determined by empiric fixed activity method for the treatment of DTC with diffuse pulmonary metastases.

Combined effects of all-trans-retinoic acid and trichostatin A on the induction of differentiation of thyroid carcinoma cells.

BACKGROUND AND OBJECTIVE: The effectiveness rate of all-trans-retinoic acid (RA) is only about 30% in the clinical application of inducing thyroid carcinoma differentiation. In addition, there are severe toxic side effects, which limit its clinical application. Phase I-III clinical studies have been conducted on the combined application of two or more kinds of inductors in tumors. Nevertheless, the combination of RA with histone deacetylase inhibitors is rarely reported. This article studied the effects of differentiation for papillary thyroid carcinoma and follicular thyroid carcinoma cell lines induced by RA combined with trichostatin A (TSA), enhancing the effect of induction, while reducing the toxic side effects of a single drug, to provide a theoretical basis for preclinical trials. METHODS: After incubation with RA combined with TSA, K1 and FTC-133 were grouped into Group 1 (RA 10(-4) mol/L plus TSA 1.65 x 10(-7) mol/L), Group 2 (RA 1 x 10(-4) mol/L plus TSA 3.31 x 10(-7) mol/L), Group 3 (RA 10(-5) mol/L plus TSA 1.65 x 10(-7) mol/L), Group 4 (RA 1 x10(-5) mol/L plus TSA 3.31 x 10(-7) mol/L) by four varied concentrations and three time points (12 h, 24 h, and 48 h). The cell proliferation, conformation, toxic effect, and induced differentiation on K1 and FTC-133 cell lines were studied microscopically with hematoxylin-eosin (HE) to observe cell quantity and morphology, methyl-thiazolyl-tetrazolium (MTT) to calculate cell survival rates, and electrochemiluminescence analysis measuring in vitro thyroglobulin (Tg) levels. RESULTS: The research showed that K1 and FTC-133 cells had cell spacing increases, with an outer edge of smooth, nuclear chromatin condensation after RA combined TSA. Survival rate were assessed by an analysis of variance (ANOVA) by concentration and time point, F values of K1 and FTC-133 were 23.52 and 170.14, and 57.09 and 224.35, respectively. There were significant differences for both cells (P < 0.01). The SNK analysis indicated that survival rates were in the order of Group 2 < Group 1 < Group 4 < Group 3. Tg was also assessed by ANOVA, F values of K1 were 69.63 and 101.07, and F values of FTC-133 were 79.77 and 81.72 (P < 0.01). Group 1 was compared with Group 3 of K1 and FTC-133 by the least significant difference (LSD) method, and there was no statistical difference between the two group (P = 0.06, 0.2, respectively; P > 0.05), yet a significant difference was seen between the other Groups. CONCLUSIONS: Lower concentrations of RA combined with lower concentrations of TSA have both inhibited cell proliferation, decreased toxicity of the drugs, and increased the effect of K1 and FTC-133 cell differentiation. The mechanism of action may be that TSA has pretranscription DNA regulation and that RA has posttranscriptional signal regulation to enhance the effects of inhibited proliferation and differentiation of cells by transcription systems.

[The effects of antisense oligonucleotides bcl-2/bcl-xl and bcl-2 on proliferation and apoptosis of breast cancer cells].

OBJECTIVE: To evaluate the effects of phosphorothioate antisense oligonucleotides (ASON) bcl-2/ bc-xl ASON and bcl-2 on the proliferation and apoptosis of breast cancer cells, MCF-7. METHODS: 1) bcl-2 ASON and bcl-2/bcl-xl ASON were transfected into MCF-7 cells with anionic long circulating liposomes (NA), cationic LCL (PA), respectively. 2) After incubation with bcl-2 ASON (FB1), bcl-2/bcl-xl ASON (FB2), NA loaded with bcl-2 ASON (NA-S) or bcl-2/bcl-xl ASON(NA-D), PA loaded with bcl-2 ASON(PA-S) or bcl-2/bc-xl ASON (PA-D) for 24 h, their inhibition on MCF-7 cells were evaluated by using HE staining, methythiazolyltetrazolium (MTT) and flow cytometry (FCM). RESULTS: The significant difference of nuclear condensation, chromatin fragmentation and apoptotic bodies in MCF-7 cells, typical of apoptotic cell death was observed in groups of bcl-2/ bcl-xl bispecific ASON by compared with that of bcl-2 ASON treatment. The fluorensence intensities of bcl-2 in groups of NA-D and NA-S, PA-S and PA-D, FB1 and FB2 were 1.92+/-0.08 and 2.83+/-0.16 (P=0.028); 4.20+/-0.18 and 2.85+/-0.57 (P=0.001); 5.70+/-1.16 and 4.35+/-0.11 (P=0.001), respectively. The cell survival rates at 24 h of NA-D and NA-S, PA-S and PA-D, FB1 and FB2 were (0.32+/-0.03)% and (0.58+/-0.07)% (P=0.014); (0.71+/-0.03)% and (0.45+/-0.04)% (P=0.014); (0.88+/-0.04)% and (0.57+/- 0.05)% (P=0.003), respectively. CONCLUSION: The bcl-2/bct-xl bispecific ASON could inhibit bcl-2 expression and induce apoptosis of breast cancer cells more efficiently than that treated with bcl-2 ASON alone.

AFP promoter enhancer increased specific expression of the human sodium iodide symporter (hNIS) for targeted radioiodine therapy of hepatocellular carcinoma.

The sodium iodide symporter (NIS) present in the membranes of thyroid cells is responsible for the capacity of the thyroid to concentrate iodide. This allows treatment of thyroid cancers with (131)I. We propose to enlarge the therapeutic strategy to hepatocellular carcinomas by using hepatoma-specific promoter and enhancer for targeted radiotherapy. We constructed a recombinant adenovirus encoding hNIS gene under the control of AFP promoter and enhancer (AdPLEN). After being infected with AdPLEN, HepG2 cells (high AFP-expression hepatoma cells) showed 6 times greater perchlorate-sensitive (125)I uptake than did SMMC7721 cells (low/no AFP-expression hepatoma cells), 30 times higher than Hela (human cervix tumor cells), and noninfected HepG2 cells. These results demonstrate that the AdPLEN vector can function in high AFP expression hepatoma cells. In addition, AdPLEN-infected tumor cells were selectively killed by exposure to (131)I, as revealed by clonogenic assays. To assess the efficiency of this target gene therapy strategy in vivo, we injected the AdPLEN vector in human tumors (HepG2 cells) established in nude mice. Western blotting analysis confirmed the expression of the NIS protein in the tumor. Two days after intratumoral injection, AdPLEN-treated tumors could specifically accumulate (131)I, as revealed by imaging experiments. Altogether, these data indicate that AdPLEN is very efficient in triggering and enlarging significant iodide uptake by hepatocellular carcinomas, outlining the potential of this novel cancer gene therapy approach for a targeted radiotherapy.

Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: clinical phase I/II trials.

PURPOSE: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine (131I) metuximab injection (Licartin), a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody Fab'2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. METHODS AND MATERIALS: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. RESULTS: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p = 0.0019). CONCLUSION: Iodine (131I) metuximab injection is safe and active for HCC patients.

[Construction of the recombinant adenovirus carrying sodium/iodide symporter gene].

Human Sodium/Iodide symporter gene cDNA was amplified from thyroid tissue of the patient suffering from Graves disease by RT-PCR, and T/A cloned into pGEM-TEasy-NIS for sequencing, subcloned into shuttle plasmid pAdTrack-CMV which contained a green fluorescent protein (GFP) gene, and then forwarded to homologous recombinant in the bacteria BJ5183 that already contained AdEasy-1 plasmid. Positive recombinant adenovirus vector was selected, packaged and amplified in the 293 cells to obtain recombinant adenovirus. The results showed that the recombinant AdNIS was correctly constructed and confirmed by restriction enzyme analysis and PCR. The viral titer was 2. 5 - 3 x 10(9) efu/ml. So, the recombinant adenovirus vector carrying hNIS was successfully constructed, thus providing a basis for researches on 131I therapy in nonthyroid carcinoma.

[Preparation of 125I-oligonucleotide-long-circulation liposomes].

OBJECTIVE: To investigate the preparation and the encapsulation efficiency of 125I-oligonucleotide(ON)-long-circulation liposomes (LCL). METHODS: (1) Oligonucleotide was labeled with 125I using thallium chloride tetrahydrate (TICl3) as an oxidizing agent. 125I-oligonucleotide was separated from free 125I by Sephadex G25 column chromatography. The following radiolabeling efficiency, radiochemistry purity and specific radioactivity were obtained respectively. Subsequently, the stability of 125I-ON was observed. (2) 125I-ON-LCL were prepared by means of reverse-phase evaporation. The quality of 125I-ON-LCL was evaluated after the crude LCL were repeatedly extruded through 400 nm, 200 nm, 100 nm polycarbonate membranes consecutively. Results (1) The radiolabeling efficiency, radiochemistry purity and specific radioactivity of 125I-antisense oigonucleotide (ASON) were (72.80 +/- 0.68)%, (98. 33 +/- 0.39)% and (0.63 +/- 0.11) MBq/microg; of 125I-sense oigonucleotide (SON) were (72.21 +/- 0.60)%, (98.28 +/- 0.36)%, (0.63 +/- 0.14) MBq/microg; and of 125I-nonsense oligonucleotide (NON) were (72.77 +/- 0.81)%, (98.42 +/- 0.40)%, (0.62 +/- 0.11) MBq/microg, respectively. (2) The radiochemistry purity of 125I-ON, in 0.01 mol/L HEPES buffer and human serum at 1 h, 2 h and 4 h were all above 93%, 80%, respectively. (3) LCL formulations were 115 nm in mean diameter with a PDI (polydispersibility index) of 0.103 and Zeta potential of -29.23. The encapsulation efficiencies of 125I-ASON, 125I-SON and 125I-NON were (66.21 +/- 0.21)%, (70.93 +/- 0.03)% and (67.67 +/- 0.10)% respectively. CONCLUSION: LCL were prepared in high loading efficiency for 125I-ON with small particle sizes and symmetric distributions.

[Randomized controlled trial of hydrochlorothiazide in augmenting the dose of 131I absorbed by thyroid remnant].

OBJECTIVE: Based on the rationale that the ablation of thyroid remnant can effectively reduce the risk for recurrence of differentiated thyroid carcinoma (DTC) and hence decrease the case fatality rate. This randomized controlled trial was designed to assess the value of hydrochlorothiazide in the ablation of thyroid remnant with 131I. METHODS: Thirty consecutive DTC patients with thyroid remnant after thyroid surgery were divided into two groups by randomization, the hydrochlorothiazide group received hydrochlorothiazide 25 mg tid for 4 days, the control group received placebo. Responses to treatment were evaluated by the increment of thyroid 131I uptake rate at 24 h and the augmentation of 131I absorbed dose. RESULTS: In the hydrochlorothiazide group, the 24 h 131I uptake rate was about (1.36+/-0.58) times larger than that before treatment, the absorbed dose was about (1.35+/-0.54) times larger than that before treatment. And in comparison with the control group, the 24 h 131I uptake rate of the hydrochlorothiazide group was significantly increased and the 131I absorbed dose was significantly augmented. CONCLUSION: Hydrochlorothiazide is effective for increasing 24 h 131I uptake rate and augmenting 131I absorbed dose of thyroid remnant.

Receptor binding characteristics and cytotoxicity of insulin-methotrexate.

AIM: To characterize the receptor binding affinity and cytotoxicity of insulin-methotrexate (MTX) for the potential utilization of insulin as carriers for carcinoma target drugs. METHODS: MTX was covalently linked to insulin. Insulin-MTX conjugate was purified by Sephadex G-25 column and analyzed by high performance liquid chromatography. Hepatocellular carcinoma cell membrane fractions were isolated by sucrose density gradient centrifugation. Competitive displacement of (125)I-insulin with insulin and insulin-MTX binding to insulin receptors were carried out. Cytoreductive effect of insulin-MTX on human hepatoma BEL7402 cells and human hepatocyte cell line HL7702 was evaluated using the MTT assay. RESULTS: Insulin-MTX competed as effectively as insulin with (125)I-insulin for insulin receptors. The values of Kd for insulin-MTX and insulin were 93.82+/-19.32 nmol/L and 5.01+/-1.24 nmol/L, respectively. The value of Kd for insulin-MTX was significantly increased in comparison with insulin (t=7.2532, n=4, P<0.005). Insulin-MTX inhibited the growth of human hepatoma cells (BEL7402) almost as potently as MTX. The inhibitory effect reached a peak on the 5 th day when the growth of cells was inhibited by 79% at a concentration of 5.0 microg/mL insulin-MTX. Treatment with 5.0 microg/mL of MTX and 5.0 microg/mL of insulin-MTX merely resulted in inhibition of HL7702 cells by 31.5% and 7.8% on the 5 th day. CONCLUSION: Insulin-MTX specifically recognizes insulin receptors and inhibits the growth of BEL7402 cells. These results suggest that insulin can be used as a carrier in receptor mediated carcinoma-targeting therapy.

[Long-term effects and complications of intravascular brachytherapy].

Since the introduction of percutaneous transluminal coronary angioplasty, restenosis has remained the most challenging problem facing interventional cardiologist. Intravascular radiation is a feasible and promising adjunctive therapy in restenosis treatment by suppressing both neointimal proliferation and constrictive remodeling, while there are growing concerns about its long-term effects and complications in clinical perspectives as well as dosing and paradoxical stimulation. Current comments on them may well favor the choice of comprehensive treatment protocol for clinicians.

[The radiolabeling property of oligonucleotide with 99mTc using NHS-MAG3 as a chelator].

OBJECTIVE: To explore the radiolabeling property of oligonucleotide with 99mTc using NHS-MAG3 as a bifunctional chelator. METHODS: Three 15-base single-stranded amine-derivitized oligonucleotides, which were antisense(ASON), sense(SON) and mismatched oligonucleotides(MON) of c-myc oncogene mRNA, were coupled with NHS-MAG3 and labeled with 99mTc. The labeled oligonucleotide was purified by Sephadex G25 column chromatogram, then the stability was evaluated. The labeling efficiency of ON-MAG3 was assessed 15 days, 1 month and 2 months after storage at -20 degrees C. The binding rate of 99mTc-ON with plasma protein was measured by the trichloroacetic acid precipitation method. RESULTS: The average labeling efficiency of 99mTc-ASON, 99mTc-SON and 99mTc-ON was 68.41%, 66.24% and 69.38% respectively, and the radiochemical purity was 96.98%, 95.34% and 94.62%. 99mTc-ON was stable when placed at room temperature or incubated in human serum at 37 degrees C. The labeling efficiency of ON-MAG3 did not significantly change 2 months after storage at -20 degrees C. The plasma protein binding rate of 99mTc-ON was lower than 13%. CONCLUSION: 99mTc-ON labeled with NHS-MAG3 method showed superior radiochemical characteristics. The labeling efficiency and radiochemical purity were desirable. The label was stable in serum and the binding with plasma protein was low. 99mTc-ON could be a sort of potential radiopharmaceutical for in vivo applications.

Study on the possibility of insulin as a carrier of IUdR for hepatocellular carcinoma-targeted therapy.

AIM: To evaluate the possibility of using insulin as a carrier for carcinoma-targeted therapy mediated by receptor, and to investigate the expression of insulin receptor in human hepatocellular carcinoma and the receptor binding characteristics of insulin-IUdR (iododeoxyuridine). METHODS: IUdR was covalently conjugated to insulin. Receptor binding assays of (125)I-insulin to human hepatocellular carcinoma and its adjacent tissue were performed. Competitive displacements of (125)I-insulin by insulin and insulin-IUdR to bind to insulin receptor were respectively carried out. Statistical comparisons between the means were made with paired t-test at a confidence level of 95 %. RESULTS: The data indicated that there were high- and low- affinity binding sites for (125)I-insulin on both hepatocellular carcinoma and its adjacent tissue. Hepatocellular carcinoma had a significantly higher Bmax for high affinity binding site than its adjacent liver tissue (P<0.05, t=2.275). Insulin-IUdR competed as effectively as insulin with (125)I-insulin for binding to insulin receptor. Values of IC(50)1, C(50)2, KI1 and KI2 for insulin-IUdR were 11.50+/-2.83 nmol x L(-1), 19.35+/-5.11 nmol x L(-1), 11.26+/-2.65 nmol x L(-1) and 19.30+/-5.02 nmol x L(-1) respectively, and for insulin were 5.01+/-1.24 nmol x L(-1),17.75+/-4.86 nmol x L(-1), 4.85+/-1.12 nmol x L(-1) and 17.69+/-4.81 nmol x L(-1), respectively. Values of IC(50)1 and KI1 for insulin-IUdR were significantly higher than that for insulin (P<0.01, t=4.537 and 4.813). CONCLUSION: It is possible to use insulin as a carrier for carcinoma-targeted therapy mediated by receptor.