Biokinetics of 111In-DTPA-D-Phe(1)-octreotide in nude mice transplanted with a human carcinoid tumor

The long time biokinetics of the radiolabeled somatostatin analogues 111In-DTPA-D-Phe(1)-octreotide was studied in nude mice transplanted with the human carcinoid tumor, GOT1. The results were compared with those from the patient with the original tumor. This patient has been diagnosed and later treated with 111In-DTPA-D-Phe(1)-octreotide. The animals received about 2 MBq 111In-DTPA-D-Phe(1)-octreotide (0.1 microg) by injection into a tail vein. The animals were killed 0.5 h-14 d after injection of the radiopharmaceutical. Tumor tissue and normal tissues were collected and weighed and measured for 111In activity. The 111In uptake in the tumor was higher than in all normal tissues except the kidneys. The tumor-to-normal-tissue activity concentration, TNC, increased with time for all normal tissues studied. These data were similar to those observed for the original tumor in the patient. The similar biokinetics for 111In-DTPA-D-Phe(1)-octreotide in the tumor-bearing mice and the patient makes this animal model suitable as a model for evaluation of therapy of somatostatin receptor (sstr) expressing tumors with radiolabeled somatostatin analogues. Furthermore, the increase with time of TNC both in mice and the patient indicates that long-lived radionuclides are preferred for therapy with radiolabeled somatostatin analogues.     

Biodistribution of [111In-DTPA-D-Phe1]-octreotide in dogs: uptake in the stomach and intestines but not in the spleen points towards interspecies differences

The purpose of the present study was to establish the tissue distribution in abdominal organs and the excretion of radioactivity after intravenous administration of [(111)In-DTPA-D-Phe(1)]-octreotide in healthy dogs. In five Beagle dogs computed tomography and single photon emission computed tomography (SPECT) at 24 h after injection of [(111)In-DTPA-D-Phe(1)]-octreotide revealed accumulation of radioactivity in the kidneys, gall bladder, gastric fundus and cardia, intestinal tract, but not in the spleen. These findings were confirmed by in vitro scintigraphy of single abdominal organs. This also demonstrated accumulation of radioactivity in the pancreas and located the radioactivity in the gastrointestinal tract primarily in the wall itself. In vitro autoradiography with (125)I-[Tyr(3)]-octreotide on tissue samples in two dogs revealed sst receptors in the medullary part of the kidney, the basal two-thirds of the gastric mucosa of the cardia and fundus, Peyer's patches and neural plexus of the gastrointestinal tract. No sst receptors were demonstrated in the liver, spleen, and pancreas. These results differ to findings in man, where there is uptake in the spleen but not in the stomach, most likely caused by interspecies variations in sst receptor subtype expression.     

Therapy using labelled somatostatin analogues: comparison of the absorbed doses with 111In-DTPA-D-Phe1-octreotide and yttrium-labelled DOTA-D-Phe1-Tyr3-octreotide

OBJECTIVE: We estimated the absorbed doses for (111)In-DTPA-D-Phe(1)-octreotide and (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide in the same patients in order to compare the potential effectiveness (tumour dose) and safety (kidney and red marrow dose) of these drugs for peptide-targeted radiotherapy of somatostatin receptor positive tumours. METHODS: Six patients with neuroendocrine tumours underwent quantitative (111)In-DTPA-D-Phe(1)-octreotide SPECT and (86)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scan at intervals of 1 week. All studies were performed with a co-infusion of amino acids for renal protection. PET and SPECT were reconstructed using iterative algorithms, incorporating attenuation and scatter corrections. Tissue uptakes (IA%) were measured and used to calculate residence times. Absorbed doses to tissues were estimated and the maximal allowed activity, defined as either the activity delivering 23 Gy to the kidneys (MAA(K)) or 2 Gy to the red marrow (MAA(RM)), was calculated and the resulting tumour absorbed doses were computed. RESULTS: For the MAA(K) the mean absorbed dose to the red marrow was lower for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (1.8+/-0.9 Gy vs. 6.4+/-1.6 Gy; P<0.001). The median absorbed dose to tumours for the MAA(K) was two-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide as compared to (111)In-DTPA-D-Phe(1)-octreotide (30.1 vs. 12.6 Gy; P<0.05). The median absorbed dose to tumours estimated for the MAA(RM) was 10-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (35.1 Gy vs. 3.9 Gy; P<0.05). CONCLUSIONS: This direct intra-patient comparison confirms that the use of (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide is more appropriate for therapy of somatostatin receptor bearing tumours. When using (111)In-DTPA-D-Phe(1)-octreotide, the red marrow represents the major critical organ; this can result in significant toxicity if high activities have to be administered to obtain efficient tumour irradiation.     

脂质体介导的99Tcm-反义寡聚核苷酸在荷瘤裸鼠体内分布及显像研究

目的研究脂质体介导的99Tcm-反义寡聚核苷酸在荷瘤裸鼠体内的分布及反义显像诊断结肠癌的可能性,为反义显像和反义治疗的临床应用提供实验依据.方法制作荷瘤裸鼠模型,每只小鼠尾静脉注射约0.30MBq脂质体包裹的99Tcm-反义寡聚核苷酸,于不同时间眼眶静脉采血后处死小鼠,测定不同组织中及标准源的放射性计数.荷瘤裸鼠尾静脉注入脂质体介导的99Tcm-反义寡聚核苷酸(30～90mg),于注射后不同时间显像,观察其在肿瘤组织的浓聚情况,并以脂质体介导的99Tcm标记的正义和无义寡聚核苷酸为对照.结果胃、网状内皮系统和肿瘤组织放射性浓聚较高,其次为心和血,余组织中放射性分布较少.肿瘤组织中放射性在2h时达到高峰,以后迅速降低.在2h时,脂质体介导的99Tcm-反义寡聚核苷酸能清晰显示肿瘤部位,而对照组则不能.结论脂质体介导的99Tcm-反义寡聚核苷酸可用于结肠癌的诊断,但临床应用前还需进行大量的研究.     

111In-DTPA-D-Phe1-octreotide binding and somatostatin receptor subtypes in thyroid tumors.

The purpose of this study was to evaluate the potential for therapy of thyroid tumors using the radiolabeled somatostatin (SS) analog octreotide. METHODS: Concentrations of 111In activity in human thyroid tumors and normal thyroid tissue and blood samples were determined 1-15 d after intravenous injection of 111In-diethylenetriaminepentaacetic acid-Phe1-octreotide. The results were compared with SS receptor (sstr subtype profile (by Northern blot analysis) and the relative expression of the second subtype, sstr2 (by ribonuclease protection assay, RPA). The true tumor volumes in lymph node metastases from 1 patient were estimated. In total, tissues from 68 patients were included in the study. RESULTS: The highest tumor-to-blood ratio (T/B) for medullary thyroid carcinoma (MTC) was 360; for follicular adenoma (FA), 190; for Hurthle cell adenoma (HCA), 140; and for Hurthle cell carcinoma (HCC) and papillary carcinoma (PC), 70. The corresponding value was 7-18 for normal thyroid tissue, with higher values for colloid goiter (8-48) and thyroiditis (7-120). A high T/B was related to a large fraction of tumor cells in lymph node metastases. T/Bs were higher for the tumor samples with expression of sstr2 at Northern blot analysis than for those without. All thyroid tumor types regularly expressed sstr1, sstr3, sstr4, and sstr5. sstr2 was expressed in most MTC tumors but was not detected in FA or PC and was irregularly expressed in HCA and HCC. However, RPA analysis detected sstr2 in all tumors studied. CONCLUSION: Despite the lack of sstr2 at Northern blot analysis in most of the thyroid tumors studied, high T/Bs were in general found when compared with corresponding values for normal thyroid tissue. The sometimes extremely high ratios are promising and indicate a possibility of using radiolabeled octreotide for radiation therapy of sstr-positive tumors in the future.     

Improved tumor localization of 111In labeled monoclonal antibody with chelator administration to host nude mice

Administration of calcium disodium edetate (EDTA) substantially increased the tumor:muscle ratios of nude mice injected with ¹¹¹In labeled monoclonal antibody injection of mice bearing the BRO human melanoma, but not earlier. The tumor:muscle ratios decreased during this time for animals not receiving chelator. Contemporaneously, EDTA treated mice lost whole body radioactivity more rapidly than did their untreated counterparts, suggesting that ¹¹¹In which had dissociated from the antibody-DTPA-radiometal complex was chelated and excreted. These results suggest that effective chelator treatment might improve tumor localization of radioactivity after injection of ¹¹¹In labeled antibodies.     

Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector

Intraoperative tumour detection has been used in many applications. The examined tumour forms have varied and different detector systems and radiopharmaceuticals have also been used. The aim of this study was to evaluate and compare the ability of an NaI(Tl) scintillation detector to detect primary tumours and metastases in patients with different endocrine tumour types (e.g. carcinoid tumours, endocrine pancreatic tumours and thyroid tumours) and in patients with breast carcinoma or benign thyroid lesions, on the basis of their somatostatin receptor expression after i.v. injection of ¹¹¹In-DTPA-D-Phe¹-octreotide. Thirty patients were injected with ¹¹¹In-DTPA-D-Phe¹-octreotide intravenously. Scintigraphic images were taken 1 day after injection of the radiopharmaceutical, and surgery was performed 1-7 days post injection. An NaI(Tl) scintillation detector was used for intraoperative tumour detection. Tissue samples were collected during surgery for determination of ¹¹¹In activity concentration and histopathological examination. The scintigraphic images were positive in 29 out of 30 patients. Intraoperative tumour detection was successful in 43 of 66 collected biopsies: 10 out of 11 for carcinoid tumours, 7 out of 10 for medullary thyroid carcinoma (MTC) and 14 out of 22 for breast cancer. On the basis of our findings we conclude that intraoperative tumour detection with ¹¹¹In-DTPA-D-Phe¹-octreotide using this NaI(Tl) detector can be successful especially for carcinoid tumours and endocrine pancreatic tumours, due to the relatively high activity concentrations in these tumour types, but is less successful in other forms of thyroid cancer, including MTC, and breast cancer. For successful intraoperative detection, the detector characteristics are also very important, and further improvement of the detector systems is required to increase the sensitivity and specificity.     

Detection of somatostatin receptor-positive tumours using the new 99mTc-tricine-HYNIC-D-Phe1-Tyr3-octreotide: first results in patients and comparison with 111In-DTPA-D-Phe1-octreotide

Indium- 111 labelled DTPA-D-Phe1-octreotide (DTPA-OC, OctreoScan) has been introduced into clinical routine for the detection of somatostatin receptor (SSTR)-positive tumours, which are predominantly of neuroendocrine origin. Potential further applications in other SSTR-positive cancers (e.g. small cell lung cancer, breast cancer, melanoma) have been limited mainly by the restricted availability and the high radionuclide costs. Previous attempts to introduce technetium-99m labelled analogues of octreotide have not been very successful in terms of the labelling procedure, in vivo biodistribution and/or tumour detection capabilities. The aim of this study was to assess the performance of the new 99mTc-labelled analogue HYNIC-D-Phe1-Tyr3-octreotide (HYNIC-TOC), using tricine as co-ligand, for the detection of SSTR-positive tumours in patients in comparison with 111In-DTPA-OC. Overall, 13 patients were examined using 99mTc-tricine-HYNIC-TOC. Twelve patients had proven SSTR-positive tumours, while one patient presented with an SSTR-negative tumour. In 9 of the 13 patients both tracers (99mTc-tricine-HYNIC-TOC and 111In-DTPA-OC) were used. Serial whole-body scans, spot views and/or single-photon emission tomography studies were performed. Images were qualitatively and semi-quantitatively (ROI analyses) evaluated. The biodistribution of 99mTc-tricine-HYNIC-TOC in patients showed high physiological uptake in kidneys, moderate uptake in liver and spleen and little uptake in the gut. The tracer showed predominantly renal and negligible hepatobiliary excretion. Known SSTR-positive tumour sites showed rapid and intense tracer accumulation. 99mTc-tricine-HYNIC-TOC demonstrated rapid tissue uptake within the first hour after injection and had basically no significant clearance (<20%) from normal or tumour tissue thereafter. In contrast, 111In-DTPA-OC showed continuous clearance from normal tissues as well as renal and very little hepatobiliary excretion. Nevertheless, the patterns of accumulation of 99mTc-tricine-HYNIC-TOC in tumours and normal organs were comparable to those of 111In-DTPA-OC. A lesion-by-lesion comparison showed comparable tumour detection capabilities in intrahepatic tumour sites and superior capabilities of 99mTc-tricine-HYNIC-TOC in respect of extrahepatic lesions. In conclusion, 99mTc-tricine-HYNIC-TOC shows promise as a tracer for SSTR imaging, given its favourable clinical characteristics (specific and high receptor affinity, good biodistribution, renal excretion, low radiation exposure, high imaging quality, on-demand availability) and cost-effectiveness. 99mTc-tricine-HYNIC-TOC allows earlier diagnosis (10 min-4 h) compared with 111In-DTPA-OC (4-24 h).     

P-糖蛋白对荷瘤裸鼠体内摄取18F-FDG的影响

目的 研究Bcap37及Bcap37/MDR1荷瘤裸鼠在依克立达(GH20918)干预前后的18F-FDG摄取变化,在活体内评价P-gp对18F-FDG摄取的影响.方法 分别用人乳腺癌Bcap37细胞及转MDR1基因的Bcap37(Bcap37/MDR1)细胞建立荷瘤裸鼠模型.荷瘤裸鼠培F-FDG microPET动态采集:10只荷瘤裸鼠(Bcap37及Bcap37/MDR1荷瘤裸鼠各5只)经尾静脉给予7.4 MBq 18F-FDG,给药后立即采集,共采集90 min,得到各个时间段的动态显像图,绘制ROI的TAC.隔日相同采集及处理方法,尾静脉给予含GF120918(按体质量2.0 mg/kg)的18F-FDG 7.4 MBq,获得GF120918干预后肿瘤组织18F-FDG摄取的TAC,观察GF120918干预前后TAC的变化.另取10只荷瘤裸鼠(Bcap37及Bcap37/MDR1荷瘤裸鼠各5只),行18F-FDG microPET静态显像,并比较GF120918干预前后肿瘤组织的SUV mean的变化.数据分析采用两样本t检验.结果 Bcap37荷瘤裸鼠肿瘤组织在GF120918干预前后的TAC差异元统计学意义,GF120918可明显增加Bcap37/MDR1荷瘤裸鼠肿瘤组织平台期18F-FDG的摄取水平.荷瘤裸鼠静态microPET显像示,GF120918干预前后Bcap37及Bcap37/MDR1荷瘤裸鼠肿瘤组织的SUVmean分别为1.028±0.045、1.052±0.028和0.712±0.031、1.015±0.043,前者干预前后的SUVmean差异无统计学意义(t=1.792,P＞0.05),后者干预前后的SUVmean差异有统计学意义(t=3.365,P＜0.05).在无GF120918存在情况下,Bcap37荷瘤裸鼠肿瘤组织的18 F-FDG摄取要高于Bcap37/MDR1荷瘤裸鼠(t=3.952,P＜0.05);在给予GF120918后,两者间18F-FDG摄取水平差异无统计学意义(t=1.835,P＞0.05).结论 18F-FDG是P-gp的底物之一,18F-FDG联合GF120918可能是一种有效、无创检测肿瘤MDR的方法.     

Pharmacokinetic study of radiolabeled anti-colorectal carcinoma monoclonal antibodies in tumor-bearing nude mice

Monoclonal antibodies (MoAbs) 17-1A and 19-9, which specifically bind human colorectal carcinoma (CRC) cells, were tested for their usefulness in localizing colorectal tumors in nude mice. One of the ¹³¹I-labeled MoAbs and an irrelevant ¹²⁵I-labeled immunoglobulin of the same isotype were injected into nude mice simultaneously bearing a human CRC and a human melanoma. The percentage of the injected dose of antibody per gram of tissue, the CRC/tissue ratios of antibody distribution, and the localization indices were calculated at various time intervals (2 h to 9 days). For both MoAbs, labeling to a specific activity of 10 Ci/g by the iodogen method gave optimum immunoreactivity. The accumulation of MoAb 17-1A in CRC reached its maximum at 5 days and remained at this level for up to 9 days postinjection. For MoAb 19-9, which detects a circulating antigen shed by the tumor into the serum, the accumulation in the CRC was maximum at 24 h, and decreased thereafter. The CRC/organ ratios and localization indices for both MoAbs increased with time in the CRC tissue, but remained low and unchanged in the melanoma and normal tissues. Using F(ab)₂ antibody fragments, faster kinetics with earlier maximum accumulation, higher tumor/organ ratios, and better localization indices were achieved than with intact MoAbs. The data obtained was useful in defining parameters which must be considered before radiolabeled MoAbs are used in cancer patients for diagnostic purposes.     

Comparison of 111In-DOTA-DPhe1-Tyr3-octreotide and 111In-DOTA-lanreotide scintigraphy and dosimetry in patients with neuroendocrine tumours

Purpose Somatostatin receptor scintigraphy with ¹¹¹In-DOTA-DPhe¹-Tyr³-octreotide (¹¹¹In-DOTA-TOC) and ¹¹¹In-DOTA-lanreotide (¹¹¹In-DOTA-LAN) has been used for staging of neuroendocrine tumours (NETs). However, the comparative diagnostic value of these radioligands on a lesion basis has not yet been established. The aim of this study was to compare the diagnostic capacity of ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy in patients with NETs, evaluating whether significant differences exist in lesion imaging with these radioligands. Furthermore, dosimetric data were compared. Methods Forty-five patients with NETs were investigated with ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy. Scintigraphic results were compared with those of conventional imaging and/or surgery in each patient, and also ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in 20 patients. Results ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy were true positive in 42/45 (93%) and 39/45 (87%) patients, and imaged 74/91 (81%) and 73/91 (80%) tumour lesions, respectively. ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN detected liver metastases in 21 and 14 patients, mediastinal metastases in seven and 11 patients, and bone metastases in two and seven patients, respectively. These radioligands revealed lesions not seen by conventional imaging in seven and eight patients, respectively, or by ¹⁸F-FDG-PET in eight and seven patients, respectively. The estimated tumour absorbed doses for ⁹⁰Y-DOTA-TOC were higher than those for ⁹⁰Y-DOTA-LAN in 14 patients, whereas the opposite was true in 12 patients. Conclusion Both ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN are suitable for imaging tumour lesions in patients with NETs and can detect lesions that may not be seen by conventional imaging and ¹⁸F-FDG-PET. Compared with ¹¹¹In-DOTA-LAN, ¹¹¹In-DOTA-TOC has a superior diagnostic capacity for liver metastases, but a lower diagnostic capacity for metastatic lesions in mediastinum and bone.     

32P-磷酸铬间质给药在荷人胰腺癌裸鼠的体内生物学分布及形态学表现

目的 研究^32P-磷酸铬(^32P胶体)瘤体间质给药治疗BALB／c—nu／nu裸鼠荷人胰腺癌(Pc-3)移植瘤时在体内相应组织中的分布、药代动力学特点及全身毒性反应。方法 51只荷瘤裸鼠，经瘤体给予不同剂量^32P胶体或尾静脉给药，分批处死，动态观察^32P胶体在裸鼠体内放射性分布和组织器官形态学表现，观察体重变化和计数WBC和PLT，测量瘤体表面放射性计数率。结果 ^32P胶体瘤体间质注射后其放射性计数率明显高于其他器官组织，器官组织放射性计数率瘤体给药明显低于尾静脉给药。增体给药有效半减期为13d。形态学检查显示给药后大部分Pc-3细胞被破坏，并出现分化较好的瘤细胞；肝、脾、肺及淋巴结等重要器官组织的辐射损伤为可逆性．未见明显骨髓抑制现象。结论 ^32P胶体瘤体间质给药是治疗胰腺癌安全、简便、有效的核素介入疗法。     

188Re-DTPA-DG的制备和荷瘤裸鼠实验研究

目的建立^188Re标记DTPA-脱氧葡萄糖（DG）的方法，观察其在荷瘤裸鼠体内分布和治疗效果。方法DTPA—DG的^188Re标记体系有氯化亚锡、葡萄糖酸钠，pH值5．5，反应体系温度为37％，反应3h，用纸层析法以生理盐水和丙酮作展开剂，测定标记物的放化纯及其在体外的稳定性。将标记物经荷乳腺癌MCF-7裸鼠尾静脉注射，于注射后1，4，8，12，24h显像。经尾静脉注射0．1ml 92．5GBq／L的^188Re—DTPA—DG，21d后观察疗效。结果^188Re—DTPA—DG的放化纯可达到95．0％。^188Re—DTPA—DG荷瘤裸鼠显像示肿瘤组织摄取高，病灶／健侧后肢对应部位放射性计数（T／NT）比值在12和24h分别为5．9和7．8。^188Re-DTPA-DG组裸鼠治疗21d后肿瘤体积[（823．6±50．58）mm^3]明显比生理盐水组[（1162．7±73．08）mm^3]小，2组间差异有统计学意义（P〈0．01），抑瘤率为29．2％。结论^188Re—DTPA—DG经荷瘤裸鼠尾静脉注射后可被肿瘤组织高选择性摄取，其对肿瘤生长抑制作用明显，可能成为肿瘤内照射治疗药物。     

Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide.

Scintigraphy with 123I-Tyr-3-octreotide has several major drawbacks as regards its metabolic behavior, its cumbersome preparation and the short physical half-life of the radionuclide. The use of another radiolabeled analog of somatostatin, 111In-DTPA-D-Phe-1-octreotide, has consequently been proposed. DTPA-D-Phe-1-octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA-D-Phe-1-octreotide is cleared predominantly via the kidneys. Fecal excretion of radioactivity amounts to only a few percent of the administered radioactivity. For the radiation dose to normal tissues, the most important organs are the kidneys, the spleen, the urinary bladder, the liver and the remainder of the body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In-DTPA-D-Phe-1-octreotide scintigraphic imaging of various somatostatin receptor-positive tumors was obtained 24 hr after injection. In the six patients studied, tumor localization with 123I-Tyr-3-octreotide and with 111In-DTPA-D-Phe-1-octreotide were found to be similar. However, the normal pituitary is more frequently visualized with the latter radiopharmaceutical. In conclusion, 111In-DTPA-D-Phe-1-octreotide appears to be a sensitive somatostatin receptor-positive tissue-seeking radiopharmaceutical with some remarkable advantages: easy preparation, general availability, appropriate half-life and absence of major interference in the upper abdominal region, because of its renal clearance. Therefore, 111In-DTPA-D-Phe-1-octreotide may be suitable for use in SPECT of the abdomen, which is important in the localization of small endocrine gastroenteropancreatic tumors.     

Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector.

Intraoperative tumour detection has been used in many applications. The examined tumour forms have varied and different detector systems and radiopharmaceuticals have also been used. The aim of this study was to evaluate and compare the ability of an NaI(T1) scintillation detector to detect primary tumours and metastases in patients with different endocrine tumour types (e.g. carcinoid tumours, endocrine pancreatic tumours and thyroid tumours) and in patients with breast carcinoma or benign thyroid lesions, on the basis of their somatostatin receptor expression after i.v. injection of 111In-DTPA-D-Phe1-octreotide. Thirty patients were injected with 111In-DTPA-D-Phe1-octreotide intravenously. Scintigraphic images were taken 1 day after injection of the radiopharmaceutical, and surgery was performed 1-7 days post injection. An NaI(T1) scintillation detector was used for intraoperative tumour detection. Tissue samples were collected during surgery for determination of 111In activity concentration and histopathological examination. The scintigraphic images were positive in 29 out of 30 patients. Intraoperative tumour detection was successful in 43 of 66 collected biopsies: 10 out of 11 for carcinoid tumours, 7 out of 10 for medullary thyroid carcinoma (MTC) and 14 out of 22 for breast cancer. On the basis of our findings we conclude that intraoperative tumour detection with 111In-DTPA-D-Phe1-octreotide using this NaI(T1) detector can be successful especially for carcinoid tumours and endocrine pancreatic tumours, due to the relatively high activity concentrations in these tumour types, but is less successful in other forms of thyroid cancer, including MTC, and breast cancer. For successful intraoperative detection, the detector characteristics are also very important, and further improvement of the detector systems is required to increase the sensitivity and specificity.     

USPIO-PEG-sLeX 分子探针在裸鼠鼻咽癌移植瘤模型 MRI 的初步研究

目的：通过超顺磁性氧化铁(USPIO)螯合唾液酸化酶 X(sLeX )形成靶向内皮细胞黏附分子-1(ELAM-1)的特异性磁共振成像的分子探针(USPIO-PEG-sLeX ),并探讨其在鼻咽癌移植瘤的应用价值。方法利用物理沉积方法合成 USPIO 纳米颗粒,通过 PEG 修饰形成 USPIO-PEG-sLeX 。裸鼠鼻咽癌移植瘤模型分为实验组和对照组,分别经尾静脉注入 USPIO-PEG-sLeX 和USPIO-PEG 前后进行 MR T2 mapping 成像,比较分析注射对比剂前后移植瘤的 T2值变化。结果USPIO-PEG-sLeX 具有良好表征。对照组和实验组的鼻咽癌移植瘤的平扫 T2值差异无统计学意义(P >0.05),增强扫描后2组的 T2值下降,2组的 T2值差异有统计学意义(P <0.05);实验组的强化率更低,2组的强化率差异有统计学意义(P <0.05)。实验组中瘤体与肌肉的强化率差异有统计学意义(P <0.05)。结论USPIO-PEG-sLeX 纳米磁性颗粒有望作为鼻咽癌 ELAM-1表达的靶向对比剂,在非创伤动态监测 ELAM-1的表达方面具有良好的潜在应用前景。     

I-labelling of an internally Se-labelled monoclonal antibody—Biodistribution in tumour-bearing nude mice

A monoclonal antibody, C215, was first internally labelled with ⁷⁵Se-methionine and then labelled with ¹²⁵I. The biodistribution of the dual-labelled [¹²⁵I][⁷⁵Se]C215 was studied in tumour-bearing nude mice killed 3 days after injection. The biodistribution of the dual-labelled [¹²⁵I][⁷⁵Se]C215 was compared with the biodistribution of single-labelled [¹³¹I]C215 and [⁷⁵Se]C215. Iodine-labelled antibodies seem to be damaged during iodination, affecting the disappearance rate and tumour uptake. There were no signs of dehalogenation of circulating antibodies or antibodies taken up in the tumour.     

Distribution and stability of [111In]bleomycin and its fractions in tumor-bearing mice

The tissue distributions in glioma-bearing mice given injections of [¹¹¹In]bleomycin (BLM) indicated that tumor concentrations and ratios of tumor to blood, muscle and brain for [¹¹¹In]BLM-B₂ and -A₂ were higher than those for unfractionated [¹¹¹In]BLM. Autoradiographs of electrophoretic gels of urine containing [¹¹¹In]BLM or one of its fractions differed from those containing ¹¹¹InCl₃ [¹¹¹In]BLM and its fractions (A₂ and B₂) were found to be stable in vivo. The fractions may be more useful in the clinic than [¹¹¹In]BLM.     

Effect of DTPA on biodistribution of 111In-labeled monoclonal antibody in tumor-bearing mice]

To reduce the high background liver radioactivity in immunoscintigraphy using 111In-labeled monoclonal antibody (In-MoAb), we investigated the effect of diethylenetriaminepentaacetic acid (DPTA) on the in vitro stability of In-MoAb in human serum and the biodistribution of In-MoAb in tumor-bearing mice. In-MoAb was incubated for four days in human serum at 37 degrees C (pH 7.4) in a humidified atmosphere at 5% CO2. The serum sample was analyzed by high performance liquid chromatography every day. Indium-111 gradually transferred from the conjugate to the fraction of transferrin. When DTPA was added to the serum, radioactivity in this fraction disappeared completely and moved to the fraction of DTPA. The daily administration of DTPA to the mice after injection of In-MoAb reduced radioactivity in the normal tissues, especially in the liver after the second day, and improved tumor to normal tissue ratios. Scintigraphic examination also revealed apparent decrease of the liver radioactivity in the mice administered DTPA. These results indicate that 111In dissociated from the conjugate is one of the causes of nonspecific accumulation in the liver and it is possible to decrease this accumulation by the daily administration of DTPA.