Papillary thyroid microcarcinoma / 生物医学工程学杂志

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 / 生物医学工程学杂志

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.

Pharmacokinetics of injection of iodine-131 labelling MEI-TUO-XI monoclonal antibody in human body / 生物医学工程学杂志

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 / 生物医学工程学杂志

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.

Development of hypothyroidism therapy with thyroid hormone / 生物医学工程学杂志

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.

Radiobiological effect of 131I radiolabeled recombinant human epidermal growth factor on nude mice with human breast cancer / 生物医学工程学杂志

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.

Therapy for Graves' ophthalmopathy / 生物医学工程学杂志

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.

Experimental research into the inhibitory effect of 131I-recombinant human epidermal growth factor on the growth of breast cancer in vivo / 生物医学工程学杂志

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.

Preparation of liposome-mediated 99m-technetium-labeled antisense oligonucleotides of c-myc mRNA / 生物医学工程学杂志

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.

The primary applications of ¹⁵³Sm-EDTMP plus chemotherapy in the treatment of bone metastasis of lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To study the clinical effects of ¹⁵³Sm-EDTMP plus chemotherapy in the treatment of bone metastasis of lung cancer.</p><p><b>METHODS</b>One hundred and ten lung cancer patients with one metastasis [male 82 and female 28, aged from 32 to 76 yrs; squamous cell carcinoma 28, adenocarcinoma 27, small cell lung cancer (SCLC) 7, mix type 41, alveolar carcinoma 7] who did not undergo an operation were entered into this study. The patients were divided into 3 groups: ¹⁵³Sm-EDTMP therapy only (37 cases), ¹⁵³Sm-EDTMP plus chemotherapy after 3 days (42 cases), 30 days after chemotherapy plus ¹⁵³Sm-EDTMP (31 cases). The dosages of ¹⁵³Sm-EDTMP ranged from 1 111 to 2 660 MBq. The patients with SCLC were adapted CCNU, MTX and CTX; those with non-small cell lung cancer (NSCLC) were adapted MMC, VCR and DDP. Statistic analysis of the data was performed by Chi-square test.</p><p><b>RESULTS</b>Total pain relief rate for ¹⁵³Sm-EDTMP only was 89.2% , for ¹⁵³Sm-EDTMP plus chemotherapy was 92.8%, and for chemotherapy plus 153 Sm EDTMP was 90.3% . The foci disappeared in 9 cases with ¹⁵³Sm-EDTMP only, in 12 cases with ¹⁵³Sm-EDTMP plus chemotherapy, and in 9 cases with chemotherapy plus ¹⁵³Sm-EDTMP. The 1 year survival rate was 29.7%(11/37) by 153 Sm only, 40.5%(17/42) by 153 Sm plus chemotherapy, 38.7%(12/31) by chemotherapy plus ¹⁵³Sm-EDTMP.</p><p><b>CONCLUSIONS</b>¹⁵³Sm-EDTMP plus chemotherapy is effective in the treatment of bone metastasis of lung cancer.</p>

Samarium-153-EDTMP bone uptake rate and its relation to therapeutic effect / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 ).</p><p><b>CONCLUSIONS</b>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.</p>

Treatment of patients with Graves' ophthalmopathy by immunosuppressive agent and 99Tc-MDP / 生物医学工程学杂志

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.