[Papillary thyroid microcarcinoma].

The recent prevalence of ultrasonography (US) and US-guided fine needle aspiration biopsy (FNAB) can make us easily diagnose papillary carcinoma of 1.0 cm or less in maximal diameter, which is called papillary microcarcinoma. In the face of the fact that cervical lymph node metastasis and multicentricity are two prominent clinical characteristics of papillary thyroid microcarcinoma, the question How to treat papillary microcarcinoma has given rise to controversy. In this review, we discuss the clinical behavior, the appropriate therapeutic strategies, the factors affecting prognosis, and the methods for following up the patients with papillary thyroid microcarcinoma.

[A comparison on radiochemical behavior and biological property of antisense oligonucleotide labeled with technetium-99m by two methods: NHS-MAG3 versus SHNHP].

This study was undertaken to explore and compare the radiochemical behavior and biological property of antisense oligonucleotide (ASON) labeled with Technetium-99m using two methods: N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline (NHS-MAG3) versus hydrazino nicotinamide derivative (SHNH). After SHNH and NHS-MAG3 were synthesized, ASON was labeled with Technetium-99m using SHNH and NHS-MAG3 as a bifunctional chelator, separately. The stability in vivo and in vitro, the combination with plasma albumen of rabbit, the biodistribution in BALB/ C mice and the HT29 cellular uptake were compared between labeled compound 99mTc-SHNH-ASON, using SHNH as a bifunctional complex reagent, and 99mTc-MAG3-ASON, using NHS-MAG3 as a bifunctional chelator. The results revealed that the labeling rate and the stability of 99mTc-MAG3-ASON were evidently higher than that of 99mTc-SHNH-ASON (P < 0.05), the combination rate of 99mTc-MAG3-ASON with plasma albumen was markedly lower than that of 99mTc-SHNH-ASON (P < 0.05); the biodistribution of 99mTc-MAG3-ASON was markedly lower than that of 99mTc-SHNH-ASON in blood, heart, stomach and intestines (P < 0.05), slightly lower than that of 99mTc-SHNH-ASON in liver and spleen (P > 0.05), and markedly higher than that of 99mTc-SHNH-ASON in kidney (P < 0.05); the HT29 cellular uptake rates of 99mTc-MAG3-ASON was markedly higher than that of 99mTc-SHNH-ASON (P < 0.05). Therefore, the radiochemical behavior and biological property of 99mTc-MAG3-ASON labeled using NHS-MAG3 is better than that of 99mTc-SHNH-ASON labeled using SHNH.

Anti-sense oligonucleotide labeled with technetium-99m using hydrazinonictinamide derivative and N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline: a comparison of radiochemical behaviors and biological properties.

AIM: To explore and compare the radiochemical behavior and biological property of anti-sense oligonuc-leotide (ASON) labeled with technetium-99m using N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline (NHS-MAG(3)) and hydrazinonictinamide derivative (HYNIC). METHODS: After HYNIC and NHS-MAG(3) were synthesized, ASON was labeled with technetium-99m using HYNIC and NHS-MAG(3) as a bifunctional chelator. The in vivo and in vitro stability, binding rates of labeled compounds to serum albumen, biodistribution of (99m)Tc-MAG(3)-ASON and (99m)Tc-HYNIC-ASON in BALB/C mouse and its HT29 tumor cellular uptake were compared. RESULTS: The labeling efficiency and stability of (99m)Tc-MAG(3)-ASON were significantly higher than those of (99m)Tc-HYNIC-ASON (P = 0.02, and P = 0.03, respectively). (99m)Tc-MAG(3)-ASON had a significantly lower rate of binding to serum albumen than (99m)Tc-HYNIC-ASON (P < 0.05). In contrast to (99m)Tc-HYNIC-ASON, the biodistribution of (99m)Tc-MAG(3)-ASON was significantly lower in blood, heart, liver and stomach (P < 0.05), slightly lower in intestines and spleen (P > 0.05) and significantly higher in lung and kidney (P < 0.05). The HT29 tumor cellular uptake rate of (99m)Tc-MAG(3)-ASON was significantly higher than that of (99m)Tc-HYNIC-ASON (P < 0.05). CONCLUSION: (99m)Tc-MAG(3)-ASON shows superior radiochemical behaviors and biological properties than (99m)Tc-HYNIC-ASON. (99m)Tc-MAG(3)-ASON is a potential radiopharmaceutical agent for in vivo application.

[Pharmacokinetics of injection of iodine-131 labelling MEI-TUO-XI monoclonal antibody in human body].

To study pharmacokinetics of injection of iodine-131 labelling MEI-TUO-XI monoclonal antibody (hepatoma monoclonal antibody HAb18 F(ab')2) in vivo. 24 cases of primary hepatocelluar carcinoma (PHC) were equally divided into the low dose group, middle dose group and high dose group. After the relevant injection was administrated into the hepatic artery of each case, intravenous blood and urine samples were separately collected at different time for determination of the radioactive count ratio (min(-1)). The proportion of 131I-HAb18 F(ab')2 in serum of each blood sample was determined, and the radioactive count ratio (min(-1)) of druggery for each blood sample was revised according to the proportion. The pharmacokinetic parameters were calculated using DAS ver 1.0 (Drug And Statistics for Windows) program. The component of urine radiomaterial was determined and the percentages of urine radioactivity in administration dosage were calculated. The catabolism of the injection with time accorded with dynamics two-compartment model. The catabolism product was mainly free-131I and was excreted via kidney; the urine radioactivity was 47.70%-51.16% of administration dosage during 120 h after administration of drug. Therefore, the pharmacokinetics of the injection can satisfy the clinical demands. The drug dose recommended for clinical use was 27.75 MBq of the injection for each kg of human body.

[Inhibition of cell proliferation and C-myc cancer protein expression in human colon adenocarcinoma cell line HT29 with VIP-131I-ASON].

A 15-mer phosphorothioate antisense oligonucleotide (ASON) complementary to the translation start region of the C-myc oncogene mRNA was labeled with 131I or 125I and the labelled compound was linked to the vasoactive intestinal peptide (VIP) to be bound covalently to a polylysine chain so as to deliver oligonucleotide into tumor cells. The effect of the VIP as carrier on cell uptake of ASON in tissue culture was evaluated in a human colon adenocarcinoma HT29 cell line. The efficacy of VIP-131-ASON on cell growth was evaluated using the MTT assay. Expression of c-myc-encoded protein was measured by flow cytometry. Sense and nosense control Oligonucleotides with VIP carrier were used as control. The results showed that VIP competed effectively with VIP-125I-ASON to bind the HT29 cells. Cell uptake was increased 3-4 fold using the VIP carrier compared to the same dosage of naked DNA. HT29 cells treated with VIP-131I-ASON complexes exhibited 4-fold lower proliferation than those treated with 13I-ASON and 6-fold lower proliferation than those treated with radioiodinated Sense and nosense DNA. Cancer protein expression of HT29 cells treated with VIP-131I-ASON was decreased 2-fold compare with that in 131I-ASON treated cell. The use of a VIP carrier greatly increased 131I-ASON cellular uptake and inhibition of cell proliferation and C-myc cancer protein expressing in HT29 cell by radioiodinated antisense Oligonucleotides.

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.

[Preparation and biodistribution of VIP-125I-ASON].

OBJECTIVE: To prepare VIP-125I-ASON and investigate the possibility of using it as an agent for diagnostic imaging and therapy of colon carcinoma. METHODS: The iodination of a 15-base single-stranded antisense oligonucleotide (ASON) complementary to C-myc oncogene mRNA was carried out in the presence of TICl3. The radiolabeled oligonucleotide was complexed with a VIP-polylysine conjugate under certain condition. 3-5 microCi VIP-125I-ASON was injected into the tail vein of the BALB/c nude mice bearing transplanted HT29 colon carcinoma; the nude mice were killed at specific intervals after injection, and the biodistrbution of VIP-125I-ASON in the organs were calculated. RESULTS: The biodistributed experiment showed that the 125I-ASON was excreted by kidney mostly and by liver and spleen in part. The results of studies after the injection of VIP-125I-ASON differed from those of unconjugated 125I-ASON. The conjugation of VIP to the ASON resulted in a decrease in the plasma clearance of the radiopharmaceutical, which may be due to the reduction in the renal clearance of the ASON. The highest uptake of tumor tissue (5.89% ID/g at 2 h) was significantly higher than that in nude mice given unconjugated ASON (P < 0.05). Tumor to blood ratios and tumor to muscle ratios were optimal at 4 h. CONCLUSION: VIP-125I-ASON has desirable stability and higher uptake in tumor. It may provide a new sensitive mean for diagnostic antisense imaging and radiotherapy of tumor in the future.

[Radiobiological effect of 131I radiolabeled recombinant human epidermal growth factor on nude mice with human breast cancer].

The radiobiological effect of 131I radiolabeled recombinant human epidermal growth factor (131I-rhEGF) on nude mice with human breast cancer was assessed in this study. The tissue mainly uptaking 131I-rhEGF was found by tissue distribution assay in mice. The radiation breakdown of the tissue greatly collecting 131I-rhEGF was examined by biochemical test and biopsy in nude mice with human breast cancer. The tissue distribution assay of 131I-rhEGF in mice showed that 131I-rhEGF greatly accumulated in kidney, liver, spleen and blood. The biochemical test and biopsy revealed that 131I -rhEGF injected twice (dosing once is analogous to 14.58 GBq in a person with 50 kg, once every 14 days) had an effective killing effect on tumor but had no effect of radiation breakdown on kidney, liver,spleen and blood-cell forming tissue in mice with human breast cancer. Therefore, 131I-rhEGF is a drug unharmful to normal tissues in the course of the receptor-mediated target radiotherapy for breast cancer.

[Development of hypothyroidism therapy with thyroid hormone].

The management of patients with primary hypothyroidism is straightforward. Recent studies suggest, however, that standard thyroid replacement therapy with thyroxine may not be completely effective in relieving the symptoms of hypothyroidism, and that there may be a role for combined use of thyroxine and triiodothyronine (T3) in the replacement therapy. Furthermore, animal studies suggest that the direct contribution by the thyroid to circulating T3 concentrations may be important, and that thyroxine alone may not be adequate treatment for hypothyroidism. In studies on thyroidectomized rats, it was found that the achievement of normal tissue concentrations of T3 required either the thyroxine at high doses which resulted in the suppression of TSH secretion, or the combined thyroxine/T3 treatment, which was able to normalize the serum thyroxine, T3 and the TSH concentrations, and the levels of thyroxine and T3 in most peripheral tissues. If the same is true of humans, there might be a more physiological replacement regimen for hypothyroid patients other than the replacement regiment of using thyroxine alone.

Antitumor effects of radioiodinated antisense oligonuclide mediated by VIP receptor.

A 15-mer phosphorothioate antisense oligonuclide (ASON) complementary to the translation start region of the C-myc oncogene mRNA was radioiodinated to enhance its antitumor activity, and vasoactive intestinal peptide bound covalently polylysine (VIP-polylysine) was used as a carrier to deliver the oligonucleotide into VIP receptor-positive tumor cells. The antitumor activity of radioiodinated ASON conjugated to VIP-polylysine(VIP-131I-ASON) was investigated in athymic mice bearing HT29 tumor xenografts in comparison with unconjugated radioiodinated ASON(131I-ASON), unlabelled ASON (VIP-ASON) and scrambled oligonucleotide (VIP-131I-MON) conjugated to VIP-polylysine. Conjugation 125I-ASON to VIP-polylysine resulted in a 5.6-fold decrease in the plasma clearance and a 3.4-fold increase in tumor uptake of the radiopharmaceutical. Athymic mice bearing HT29 tumor xenografts were treated with 4 weekly doses of VIP-131I-ASON and the antitumor effects were assessed by use of the slope of the tumor growth curve. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing tumor growth rate 9.67-, 7.90-fold more effectively than 131I-ASON and VIP-ASON at equivalent doses of ASON. Conversely, 131I-ASON, VIP-ASON or VIP-131I-MON caused no significant effect compared with the normal saline. These data indicated that use of a VIP-polylysine carrier greatly increased HT29 tumor uptake of ASON and treatment with the VIP-131I-ASON complexes resulted in tumor growth delay in human colon cancer xenograft.

[Therapy for Graves' ophthalmopathy].

Graves' ophthalmopathy (GO) is also called thyroid-related eye disease, infiltrative ophthalmopathy, which is related with the autoimmunity of thyroid, especially hyperthyroidism. Its morbidity ragnes from five percent to ten percent of hyperthyroidism, and the morbidity of male patients is higher than that of the female patients. The treatment of severe GO is a difficult task for doctors. The therapeutic effect is not always satisfactory. In order to solve this knotty problem, researchers have been devoting themselves to the development of new therapeutic methods. Here, the development of the therapies for GO is introduced, and the trends of treatments are prospected.

Antisense imaging of colon cancer-bearing nude mice with liposome-entrapped 99m-technetium-labeled antisense oligonucleotides of c-myc mRNA.

AIM: To investigate the feasibility for antisense imaging of the colon cancer with liposome-entrapped 99 m-technetium labeled antisense oligonucleotides as tracers. METHODS: Fifteen mer single-stranded aminolinked phosphorothioate antisense oligonucleotides of c-myc mRNA were labeled with 99mTc-pertechnetate, then purified and finally entrapped with liposomes to form the labeling compounds, liposome-entrapped 99mTc-labeled antisense oligonucleotides. The LS-174-T cells (colon of adenocarcinoma cell line) were incubated with the labeling compounds to test the uptake rates of LS-174-T cells. Later on, a model of 30 tumor bearing nude mice was constructed by inoculating with 5 x 10(6) of LS-174-T cells at right flank of each nude mouse. About 10 d later, the model were administered by intravenous injection of the liposome-entrapped 99mTc-labeled antisense oligonucleotides. Then some of the tumour bearing nude mice were sacrificed at 0.5, 1, 2, and 4 h after intravenous injection, and proper quantity of liver, spleen, tumor, etc. was obtained. The tissues were counted in a gamma counter, and after correction for decay and background activity, expressed as a percentage of the injected dose. The others whose anterior and posterior whole-body scans were obtained at 1, 1.5, 2, 4, 6 and 24 h with a dual-head bodyscan camera equipped with parallel-hole low-energy collimaters. The ratios of radioactive counts in tumor to that in contralateral equivalent region of abdomen were calculated. RESULTS: The uptake rates of LS-174-T cells for liposome-entrapped 99mTc-labeled antisense oligonucleotides increased as time prolonged and reach the peak (17.77 +/- 2.41%) at 7 h. The biodistributions showed that the radioactivity in the tumor (13.46 +/- 0.20%) of injected dose was the highest at 2 h of intravenous injection of liposome-entrapped 99mTc-labeled antisense oligonucleotides, and then decreased sharply to 4.58 +/- 0.45% at 4 h. The tumor was shown clearly in the whole-body scan at 2 h of intravenous injection. The ratios, radioactive counts in tumor to that in contralateral equivalent region of abdomen (1.7332 +/- 0.2537), was the highest one at 2 h after intravenous injection of liposome-entrapped 99mTc-labeled antisense oligonucleotides. CONCLUSION: The liposome-entrapped 99mTc-labeled antisense oligonucleotides deserve being developed into radiopharmaceutics for the colon cancer imaging.

[Experimental research into the inhibitory effect of 131I-recombinant human epidermal growth factor on the growth of breast cancer in vivo].

This experiment was designed to study the effect of 131I-recombinant human epidermal growth factor (131I-rhEGF) on the growth of tumor in nude mice loaded with human breast cancer. Bioactivity of 131I-rhEGF and uptake of 131I-rhEGF in breast cancer tissue were verified using biodistribution experiment of 131I-rhEGF in the nude mice loaded with human breast cancer. The effect of 131I-rhEGF on the growth of tumor was assessed via the growth experiment of tumor in the nude mice loaded with human breast cancer. The ultrastructural change of the tumor cell treated with 131I-rhEGF was observed under transmission electron microscope, and the pathological change of the tumor tissue treated with 131I-rhEGF was detected by biopsy. The results showed that the tumor tissue of nude mice bearing human breast cancer obviously takes in 131I-rhEGF; that intravenous administration and intratumoral administration of 131I-rhEGF both obviously inhibit the growth of tumor, the inhibition rates (82.00% and 80.70%) being remarkably higher than that of 131I (7.49%) and that of 131I-HSA (6.91%) (P<0.05); and that intravenous and intratumoral administration of 131I-rhEGF both obviously damage and kill tumor cells. Therefore, 131I-rhEGF can inhibit the growth of human breast cancer cell in nude mice; it is a potential receptor-mediated radioactivity targeting drug for treating breast cancer.

[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.

[Evaluation of efficacy of 153Sm-EDTMP in patients with painful bone metastases of breast cancer].

OBJECTIVE: To explore the therapeutic efficacy of 153Sm-EDTMP in treating painful bone metastases from breast cancer. METHODS: Seventy-six patients with painful bone metastases from breast cancer entered the study and were treated by intravenous administration of 153Sm-EDTMP in two doses. RESULTS: Overall, 65 of 76 patients (85.52%) experienced prompt pain relief; among them 25 patients (32.89%) felt complete remission and 40 patients (52.63%) met with moderate remission. Follow-up imaging examinations were performed after each course of treatment. Complete metastatic foci disappearance was achieved in 6 cases and partial metastatic foci disappearance or regression was achieved in 16 cases, so the global effective rate was 28.95%. No major adverse effects were observed, and hematological toxicity did not exceed grade 3 in accordance to the World Health Organization criteria. CONCLUSION: 153Sm-EDTMP is safe and effective for fast palliation of painful bone metastases and for inhibition of metastatic foci from breast cancer.

[Comparison of the radioiodine thyroid uptake of diagnostic dose and therapeutic dose in patients with hyperthyroidism].

OBJECTIVE: To compare early kinetics of diagnostic dose 131I with that of therapeutic dose. METHODS: Thyroid Uptake Ratio (TUO) measurements of diagnose method on SPECT in 108 patients after oral administration 131I. RESULTS: The TUO of diagnostic dose was similar to that of therapeutic dose at 24 hours after the patients had take 131I (P > 0.05). CONCLUSION: Radioiodine thyroid uptake of diagnostic dose is consistent with that of therapeutic dose at 24 hours after oral administration of 131I.

[Study on the antisense inhibition effect of liposome-mediated radiolabled antisense oligonucleotides of c-myc mRNA].

OBJECTIVE: To ascertain whether liposome-mediated antisense oligonucleotides could inhibit the cancer cells from growing and the oncogene from expressing. METHODS: The antisense, sense and scrambled oligonucleotides for c-myc mRNA, each containing 15 bases, were synthesized elsewhere and were labeled with 99m-technetium (99mTc-DNA). Some of them were encapsulated with liposome. Then the 99mTc-DNA and the 99mTc-DNA entrapped with liposome were transfected into colon cancer cells, LS-174-T, with different radioactivity concentrations. At different time after transfection the uptake rate of cells was measured, and the reflow rate was detected at 18 h. Inhibition effect on cellular growth was tested by MTT colorimetric experiment and on the expression of c-myc by flow cytometry. RESULTS: The cellular uptake rate increased gradually after transfection within 5 hours, and that of liposome-mediated 99mTc-DNA was significantly higher than that of 99mTc-DNA. The reflow rate and fluorescence intensity of oncoprotein were 39.51 percent and 2.9860 +/- 0.3733 for antisense oligonucleotides, 44.12 percent and 4.2600 +/- 0.2218 for sense oligonucleotides, and 63.92 percent and 5.2620 +/- 0.8562 for mismatched oligonucleotides. The reflow rate and fluorescence intensity of liposome-entrapped 99mTc-labeled antisense oligonucleotide were significantly lower than those of sense and scrambled oligonucleotides. CONCLUSION: The liposome-mediated 99mTc-labeled antisense oligonucleotides could prohibit the cancer cells from growing and the oncogene from expressing.

[Preparation of liposome-mediated 99m-technetium-labeled antisense oligonucleotides of c-myc mRNA].

To explore the preparation method of liposome-mediated 99m-technetium-labeled antisense oligonucleotides of c-myc mRNA and lay foundations for antisense imaging and treatment, antisense oligonucleotides (DNA) with 15 bases and di-functional chelate, hydrazino nicotinamide derivatives, were synthesized. After DNA combined with chelate, they were labeled with 99m-technetium to form compounds, 99mTc-chelate-DNA (99mTc-DNA), and were purified through Sep-Pak reverse column(C18, Waters) by using methanol and water as eluent. The leaching curve was made; the labeling efficiency was calculated. The products were then encapsulated with cation liposome to form liposome-mediated 99mTc-DNA. The radiochemical purity and stability of the liposome-mediated 99mTc-DNA were tested through strip chromatography. The labeling efficiency was 63.37% +/- 3.51% at the radioactive concentration of 1480 MBq, 62.52% +/- 3.69% at that of 740 MBq, 59.82% +/- 5.12% at that of 592 MBq. There were no significant differences between these labeling efficiencies. The radiochemical purity was 96.47% +/- 3.01%. The liposome-mediated radiolabeled antisense oligonucleotides were stable after incubation with water or serum. Therefore liposome-mediated radiolabeled antisense oligonucleotides could be obtained through hydrazino nicotinamide derivatives as di-functional chelate and liposome as vector.

[Treatment of patients with Graves' ophthalmopathy by immunosuppressive agent and 99Tc-MDP].

The purpose of this study was to evaluate the efficacy of immunosuppressive agents, 99Tc-MDP and both of them in treating patients with Graves' ophthalmopathy(GO). The efficacy was evaluated by randomized controlled trial involving a total of 66 patients. In 22 patients treated with immunosuppressive agents, the general efficacy rate was 19/22, the incidence rate of serious side-effect was 8/22. In 20 patients treated with 99Tc-MDP, the general efficacy rate was 17/20, the incidence rate of serious side-effect was 2/20. In 24 patients treated with immunosuppressive agents and 99Tc-MDP, the general efficacy rate was 22/24, the incidence rate of serious side-effect was 2/24. The results suggested that in the treatment of Graves' ophthalmopathy, when satisfactory efficacy was obtained, the serious side-effect and 'rebound' of symptom could be avoided by using immunosuppressive agents in combination with 99Tc-MDP.

Samarium-153-EDTMP bone uptake rate and its relation to therapeutic effect.

OBJECTIVE: To evaluate the measurement of Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) bone uptake rate using whole-body scintigraphy and analyze the relationship between bone uptake rate and therapeutic effect. METHODS: Sixty-six patients with painful bony metastases from prostate (n = 15), lung (n = 20), breast (n= 18), nasopharyngeal carcinoma (NPC) (n=5), colon (n=2), kidney (n=2) and unknown cause (n=4) carcinoma were examined with whole-body scintigraphy 10 min and 5 h post administration of (153)Sm-EDTMP. Bone uptake rate was then calculated. (1 ) Complete response (CR): disappearance of > 2 metastases, Karnofsky Performance Score (KPS) increase > 20, moderate or complete remission of bone pain 7 d post injection of (153)Sm-EDTMP. (2) Partial response (PR): disappearance of 1-2 metastases, KPS increase 10-20, moderate remission of bone pain in 3 wk. (3) Non-response (NR): no disappearance or shrinkage of metastases, KPS increase < 10, no or slight remission of bone pain. RESULTS: The range of bone uptake rate in 66 patients was 31 .9% - 86.6% (mean = 56. 0%). The bone uptake rate in the CR group (17 cases, 25.7%), PR group (24 cases, 36.4%), and NR group (25 cases, 37.9%) was 52.4% - 86.6% (mean = 68.7%), 43.7% - 70.4% (mean = 58.3%), and 31.9%- 51 .5% (mean = 41 . 0%) respectively. Statistical analysis showed that there was a significant difference between the CR and PR groups ( t = 4.258, P = 0.001 ) as well as between PR and NR groups ( t = 8.48,P = 0.001 ). CONCLUSIONS: Using a simple and reliable whole-body scintigraphic technique to calculate prospectively the bone uptake rate, we have, for the first time in China, reported the relationship between bone uptake rate and therapeutic effect. This allows nuclear medicine physicians to calculate a safe and effective dose of (153)Sm-EDTMPin individual patients to palliate bone cancer pain without myelotoxicity.