Enhanced uptake of 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone treatment: potential for increasing delivery of therapeutic agents.

Following androgen ablation therapy, skeletal metastases from prostate cancer appear in some instances to show an increase in 99Tcm-methylene diphosphonate (99Tcm-MDP) uptake. Such a phenomenon could represent a mechanism to increase delivery of bone-seeking therapeutic agents to skeletal metastatic sites. The aim of this study was to characterize more precisely the potential increase in 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone therapy. Baseline bone scans were performed within 1 week of onset of hormone therapy in patients with stage D2 prostate cancer followed by multiple repeat bone scans for up to 4-6 weeks. The count density within metastatic lesions was divided by the average count density from several areas of normal bone to obtain a lesion to normal bone uptake ratio (L/N) for each lesion in each scan. Altogether, 61 skeletal metastases were identified on bone scans from five subjects. Eighty-four percent (51/61) of these lesions showed an increase in 99Tcm-MDP activity relative to normal bone following initiation of hormone therapy with a mean peak increase of 39%. Thirty-nine of these 51 metastatic lesions showed maximum uptake at 3 weeks post-onset of hormone treatment. From our findings, it appears that approximately 3 weeks following initiation of hormone blockade, most skeletal metastases from prostate cancer will demonstrate significantly enhanced 99Tcm uptake relative to normal bone. Consequently, it may be possible to improve the uptake and effectiveness of therapeutic bone-seeking radiopharmaceuticals by administering these agents following hormone therapy in patients with prostate cancer metastases.     

Bone-scan-like pattern with 99Tcm(V)-DMSA scintigraphy in patients with osteomalacia and primary hyperparathyroidism

The aim of this study was to assess the role of 99Tcm(V)-dimercaptosuccinic acid (99Tcm(V)-DMSA) scintigraphy in the evaluation of patients with metabolic bone disease. The study group comprised eight women aged 17-72 years, six with osteomalacia and two with primary hyperparathyroidism. Six patients were imaged scintigraphically before their treatments were started, whereas the other two underwent treatment during the time of examination. All six patients who had not previously been treated had prominent skeletal 99Tcm(V)-DMSA uptake, revealing a bone-scan-like pattern. In the two patients receiving medical therapy, their 99Tcm(V)-DMSA scans revealed a normal physiological distribution. Many of the fracture and pseudofracture sites detected on bone scans were also discerned with 99Tcm(V)-DMSA scintigraphy. Our results suggest that 99Tcm(V)-DMSA scintigraphy might have the potential as a screening method in patients with metabolic bone disease.     

Uptake of 99Tcm-MDP in lung metastasis from osteosarcoma: clinical and animal studies

Bone scintigraphy was performed in 17 patients with previously known lung metastases of osteosarcoma. 99Tcm-MDP uptake was observed in all primary bone lesions but lung metastatic lesions were positive in only six patients (35%). 99Tcm-MDP uptake by lung metastases was significantly correlated with bone and osteoid formation in the metastatic lesions and preoperative serum ALPase values. These clinical observations were confirmed by using nude mice transplanted with human lung metastatic osteosarcoma. 99Tcm-MDP scintigraphy appears to be useful for detecting lung metastases of osteosarcoma only in a selected group of patients.     

The role of 99mTc(V)-DMSA scan as compared to 99mTc-MDP and CT scans in imaging the primary tumor and metastases of osteosarcoma

The oncophilic complex of technetium-99m labeled pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) has been successfully used for the detection of primary and metastatic medullary thyroid cancer and for imaging various soft tissue tumors like lung, brain and prostate cancer. In this article, the role of 99mTc(V)-DMSA in the diagnosis of the primary tumor and metastases of osteosarcoma patients as compared to the 99mTc-MDP scan and the CT scan was studied. Twenty-eight patients with bone disease were referred to the Nuclear Medicine Department of Saint Savas Oncology Hospital in Athens from the Orthopedics Department of the same Hospital. From them, 18 (Group A) had osteosarcoma, 7 (Group B) osteomyelitis and 3 (Group C) bone fractures. The final diagnosis was made after fine needle aspiration biopsy. All patients were subjected to the 99mTc(V)-DMSA scan, the standard bone scan (99mTc-MDP) and CT scan. Group A patients showed a selective uptake of 99mTc(V)-DMSA in the primary tumor region. No abnormal 99mTc(V)-DMSA uptake was observed in the patients of Groups B and C. The 99mTc(V)-DMSA scan was found to be superior to the 99mTc-MDP and the CT scans in identifying metastases of osteosarcoma. Sensitivity was 100%, 86% and 98% respectively.     

^99mTc（V）—DMSA骨显像诊断骨转移瘤的临床价值

目的：评价99mTc（V）－DMSA显像在骨转移瘤诊断中的意义。材料和方法：对91例疑骨转移瘤患者行99mTc（V）DMSA全身显像，并与99mTc-MDP全身骨显像及其它检查对比。结果：74例证实存在骨转移瘤者，99mTc．MDP骨显像均显示异常放射性浓聚，99mTc（V）-DMSA显像72例显示了与99mTc-MDP显像某些相同部位的放射性浓聚，2例99mTc（V）DMSA显像阴性。17例骨良性病变，99mTc－MDP骨显像显示轻度异常放射性浓聚，而99mTc（V）-DMSA显像却未见异常的放射性浓聚。结论：99mTc（V）－DMSA诊断骨转移瘤的特异性比99mTc-MDP骨显像高，在骨良恶性肿瘤鉴别诊断中具有重要的临床价值。     

24-Hour/4-hour ratio of technetium-99m methylene diphosphonate uptake in patients with bone metastases and degenerative bone changes

The uptake of [99mTc]MDP in metastatic lesions of the vertebrae was compared with the uptake in normal vertebrae. The ratio of these lesion-to-nonlesion uptakes at 4 and 24 hr was called the 24-hr/4-hr ratio (TF ratio). A similar ratio was measured for lesions in the spine due to degenerative bone disease. Lesions in vertebrae with degenerative bone disease and treated metastases had a significantly lower TF ratio than lesions in vertebrae with untreated bone metastases. These findings suggest that the TF ratio might be a reliable method for separating metastatic lesions from degenerative changes in the vertebral column, and could be especially useful in cancer patients whose bone scans demonstrate a single lesion in the spine.     

Comparison of99mTc(V)-DMSA,201Tl and99mTc-MIBI imaging in the follow-up of patients with medullary carcinoma of the thyroid

Radionuclide scanning with tumour-seeking agents such as pentavalent technetium-99m dimercaptosuccinic acid [^99mTc(V)-DMSA], thallium-201 and technetium-99m sestamibi (MIBI) has been reported to be useful in the detection of medullary thyroid carcinoma (MTC). We undertook a study in 14 MTC patients to determine the comparative imaging potential of²⁰¹Tl, MIBI and^99mTc(V)-DMSA in the detection of recurrent or metastatic MTC. All patients underwent total thyroidectomy and had persistently elevated serum calcitonin levels after the surgery. Scintigraphic studies were carried out 20 min after the injection of 111 MBq of²⁰¹Tl or 555 MBq of MIBI and 2 h following the injection of 370 MBq of^99mTc(V)-DMSA. All scintigraphic findings were correlated with contemporaneous CT or MRI studies. CT, MRI and bone scans showed 42 (26 bone, 16 soft tissue) metastatic sites in 11 of the 14 patients. In the remaining three patients no lesions were detected during diagnostic evaluation.^99mTc(V)-DMSA showed all of the soft tissue metastases but could not show two bone lesions. On the other hand, MIBI imaging was false-negative in 22 (52%) sites and²⁰¹Tl was false-negative in 34 (80%) sites. Overall, lesion detection sensitivities for^99mTc(V)-DMSA, MIBI and²⁰¹Tl were 95%, 47% and 19% respectively. We conclude that^99mTc(V)-DMSA is clearly superior to MIBI and²⁰¹Tl in the follow-up of MTC patients.     

99Tcm-citrate: a new bone imaging radiopharmaceutical

99Tcm-citrate has been shown to incorporate irreversibly in the skeleton with a biodistribution different to that on a conventional bone scan. The aims of this study were to confirm the bone-imaging properties of 99Tcm-citrate, to identify the variabilities influencing its skeletal uptake, to compare its uptake in bone with that of 99Tcm-MDP and to assess its possible role in bone scintigraphy. Appropriate animal and human studies (n = 45) were conducted. The 3 h lesion-to-bone ratio of 99Tcm-citrate was compared with that of 99Tcm-MDP in more than 150 lesions, including osteoblastic sites (Group A), lesions undergoing treatment or healing (Group B), and degenerative or old healed lesions (Group C). The uptake ratio was classified as concordant (< 20% variation), mildly discordant (20-50% variation) or significantly discordant (> 50% variation). Animal experiments showed most bone uptake of 99Tcm-citrate when prepared at a pH of 6.0-6.5. The two radiopharmaceuticals appeared to compete for bone uptake, suggesting related but different sites of bone accumulation. The 99Tcm-citrate/99Tcm-MDP uptake ratio in Group A was concordant (mean +/- S.D. = 0.92 +/- 0.15), while Group C lesions had a significantly lower 99Tcm-citrate/99Tcm-MDP uptake ratio (0.34 +/- 0.24, P < 0.01). A comparison of Group B lesions showed wide variation in intensity and area of involvement in many lesions (uptake ratio < 0.5 or > 1.5 in 13 of 30 sites). We conclude that 99Tcm-citrate has a different site of bone localization than phosphonates, possibly in the organic matrix. Although its skeletal uptake is lower than that of 99Tcm-MDP, it may have better specificity in differentiating osteoblastic from degenerated or healed bony lesions, and therefore be useful in predicting healing of bone secondaries, fractures or osteomyelitic lesions.     

The role of 99Tcm-sestamibi scintigraphy in the staging and prediction of the therapeutic response of stage IV neuroblastoma: comparison with 131I-MIBG and 99Tcm-MDP scintigraphy

In this study, we investigated prospectively the diagnostic role of 99Tcm-MIBI for staging and for predicting the therapeutic response of stage IV neuroblastoma compared with 131I-MIBG imaging and 99Tcm-MDP bone scintigraphy. Nine patients (4 girls and 5 boys aged 1-7 years) with suspected or proven stage IV neuroblastoma were studied with 99Tcm-MIBI at initial diagnosis and after 12-18 months of multidrug therapy. After the injection of 80 MBq.kg-1 99Tcm-MIBI, early (10 min) and delayed (1 h) images were obtained. The data were correlated with 131I-MIBG scans, bone scintigraphy, ultrasound, computed tomography and/or magnetic resonance imaging, and bone marrow biopsy. Eight of nine primary tumours and 41 metastatic lesions were detected by 131I-MIBG scintigraphy. None of the primary lesions demonstrated significant 99Tcm-MIBI accumulation. Sestamibi was positive in 16 of 41 MIBG-avid metastatic lesions. After six courses of multidrug chemotherapy, 30 131I-MIBI-avid neuroblastoma metastases that were 99Tcm-MIBI-negative at the time of diagnosis still did not show significant sestamibi accumulation. Follow-up demonstrated that all lesions that were 99Tcm-MIBI-avid at the time of diagnosis remained negative. Of these 16 lesions, seven were positive for 131I-MIBG accumulation with no reduction in size, and nine showed resolution after therapy. New metastatic foci detected by MIBG scintigraphy did not accumulate 99Tcm-MIBI. Clinical evaluation of patients with no 99Tcm-MIBI uptake in primary and secondary sites of neuroblastoma confirmed that they were resistant to multidrug chemotherapy. All 99Tcm-MIBI-positive lesions, irrespective of clinical outcome, demonstrated significant clearance of tracer on the delayed images. We conclude that 99Tcm-MIBI has no role in the staging of neuroblastoma. Sestamibi is a well-documented transport substrate for P-glycoprotein-related multidrug resistance and serial imaging may provide prognostic information on the therapeutic value of chemotherapy.     

A computer assisted comparison of 99Tcm-methylene-diphosphonate and 99Tcm-pyrophosphate bone imaging.

A total of 350 patient studies were carried out using clinical trials' batches of the Technetium (MDP) agent for bone scintigraphy (The Radiochemical Centre), and a commercially available Technetium pyrophosphate agent (CIS). The bone seeking properties of 99Tcm Sn-methylene-diphosphonate (MDP) and 99Tcm Sn-pyrophosphate (PYP) were evaluated by their comparative uptake in compact bone, cancellous bone and soft tissue using a region-of-interest technique. From these data uptake ratios were computed in order to correlate the values with (a) the amount of 99Tcm-MDP injected, (b) the time after injection and (c) the age of patients examined. All ratios derived with 99Tcm-MDP were superior to those using 99Tcm-PYP and were not dependent on the amount of 99Tcm-MDP injected. Uptake ratios determined for 99Tcm-MDP (1.5 h to 2.5 h after injection) were found to be higher than those for 99Tcm-PYP 2.5 to 3.5 h after injection. Soft tissue accumulation of 99Tcm-MDP, visible on scintiphotos, occurred only in 26% of cases but with 99Tcm-PYP, in 75% out of all cases studied. A decrease of cancellous bone/compact bone ratios with increasing age of the patients was found with both radiopharmaceuticals. This is most probably correlated with a diminished mass and/or surface of the cancellous bone in the elderly patient.     

Tc-99m(V) DMSA imaging. A new approach to studying metastases from breast carcinoma.

Combined Tc-99m MDP skeletal imaging and Tc-99m(V) DMSA whole body scans to detect metastases were performed during the follow-up of 30 patients who underwent surgery for breast carcinoma. Eight patients had normal Tc-99m MDP and Tc-99m(V) DMSA scans and were declared free of metastatic disease, further confirmed by no change in symptomatology over a 1-year follow-up period. Twenty-two patients had positive Tc-99m MDP scans with varied skeletal involvement. Tc-99m(V) DMSA scans showed matched areas of increased radiotracer concentration in bony metastases in 20 of these patients. Tc-99m(V) DMSA concentration was not seen in traumatic vertebral collapse or in coexistent osteoarthritic disease in vertebral metastatic involvement. Interestingly, Tc-99m(V) DMSA showed increased concentration in brain and liver metastases. Pentavalent Tc-99m(V) DMSA appears useful for detecting skeletal and soft-tissue metastases in breast carcinoma, and can improve the specificity of Tc-99m MDP bone scans in screening for bone metastases.     

肺癌、乳腺癌、食道癌远端骨转移特点的对比研究

目的 对比研究肺癌、乳腺癌、食道癌患者骨转移灶分布特点.方法　对肺癌、乳腺癌、食道癌患者454例进行 99Tcm-亚甲基二膦酸盐(99Tcm-MDP)SPECT全身骨显像,以上肢中远端和(或)骨盆、下肢部位发生骨转移为纳入条件,分析骨转移灶的分布特点及其在病种间的区别.结果 454例肿瘤患者中,上肢中远端和(或)骨盆、...     

The relation of radionuclide uptake by bone to the rate of calcium mineralization. II: Patient studies using 99Tcm-MDP

The relation of radionuclide uptake by bone and rate of calcification has been studied in normal vertebrae and in vertebral metastases from cancer of the prostate. Specifically, the determination of 99Tcm-MDP uptake by radionuclide scanning and the estimation of calcium concentration of trabecular bone by dual-energy computed tomography have provided the means of obtaining a relation between these parameters which was similar to that found in an animal model, in which the dependence of radionuclide uptake on the rate of mineralization was established. This relationship has enabled the experimental findings to be extrapolated to those in patient studies and has shown that in sclerotic bone lesions, the increase in 99Tcm-MDP uptake accompanying the progression of the metastases was proportional to the rate of calcification.     

Simple and reliable preparation of pentavalent 99Tcm-dimercaptosuccinic acid at alkaline pH without oxygen bubbling

We investigated a simple and reliable method for the preparation of 99Tcm-dimercaptosuccinic acid (99Tcm(V)-DMSA) without the addition of oxygen. The effect of pH, amount of reducing agent, and oxygen addition in the synthesis of 99Tcm(V)-DMSA were evaluated. At pH 9, we obtained a radiochemical yield of 95% +/- 1.2% within 10 min and a high stability until 7 h, with 92% +/- 1.5% radiochemical purity. However, at a pH lower than 9, the radiochemical yield was below 90% within 10 min, and a longer reaction time was needed to obtain a radiochemical yield above 90%. The addition of oxygen did not have an additional effect on the radiochemical yield or its stability at pH 9, whereas it increased the radiochemical yield of 99Tcm-(V)-DMSA at pH 7. It was noted that the smaller the amount of reducing agent used, the higher was the radiochemical yield obtained at pH 7. However, at pH 9, the radiochemical yield was not dependent on the amount of reducing agent. In conclusion, the synthesis of 99Tcm(V)-DMSA was more dependent on the pH of the reaction mixture than on the amount of reducing agent or the addition of oxygen. The adjustment of pH 9 was the easiest and most effective method for the synthesis of 99Tcm(V)-DMSA using a commercial kit for 99Tcm(III)-DMSA.     

Bone marrow immunoscintigraphy for the detection of skeletal metastases in patients with breast cancer

In this study, we evaluated the efficacy of bone marrow immunoscintigraphy (BMIS) for the detection of skeletal metastases in 23 patients with histologically confirmed breast cancer. All patients underwent whole-body BMIS 3-6 h after the intravenous injection of 0.20-0.33 mg of the intact anti-NCA 95 MAb BW 250/183 labelled with 259-555 MBq 99Tcm and a whole-body 99Tcm-MDP bone scan. In four patients, BMIS SPET of the lumbar spine was also performed. Serum alkaline phosphatase was determined in all patients and the level of human anti-mouse antibody (HAMA) in 16. Final diagnosis was confirmed by radiology and 2 years follow-up. Compared with the 99Tcm-MDP bone scan, BMIS demonstrated better specificity (88% vs 75%) and a better positive predictive value (92% vs 85%). There were no significant differences between BMIS and the bone scan in the detection of skeletal metastases (P > 0.05). In one patient with normal planar BMIS of the lumbar spine, SPET disclosed a metastatic lesion in the bone marrow. The correlation coefficient between BMIS and bone scan and between BMIS and serum alkaline phosphatase was r = 0.688 and r = 0.483 respectively. One patient developed a minor HAMA response after BMIS. Patients with diffuse increased activity of the skull on the bone scan had a significantly higher skull to whole body ratio on BMIS (P < 0.01). Thus BMIS can improve the specificity and positive predictive value of bone scanning in the detection of skeletal metastases, with a low HAMA response. Diffuse increased activity of the skull on bone scans could be explained by bone marrow extension. SPET scanning of the spine may improve the sensitivity of BMIS.     

The role of Tc-99m (V) DMSA scintigraphy in the diagnosis and follow-up of lung cancer lesions

Objective To define the role of Tc-99m (V) dimercaptosuccinic acid (DMSA) scanning in the detection of lung cancer (LC) and its metastases, and monitoring the response of LC lesions (LCL) to chemo/radiotherapy (TH). Methods Tc-99m (V) DMSA whole-body scans, planar thorax views, and thorax Single-photon emission computed tomography (SPECT) images were obtained both 30 min (early) and 5 h (late) after Tc-99m (V) DMSA administration in 12 small/nonsmall cell LC patients (11 men, 1 woman; mean age 59 years). Five patients also had bone scans. The same scintigraphic protocol was performed in 7 of 12 patients, 3 weeks after first-line TH. TH response was evaluated visually in all LCL and semiquantitatively in primary tumors (PT) of six patients, by comparing the tumor uptake ratios (TUR) of pre-TH and post-TH Tc-99m (V) DMSA SPECT [TUR = mean counts of region of interests (ROI) in PT/mean counts in contralateral ROI]. In seven patients, a 6-month survival was determined. Results Tc-99m (V) DMSA accumulated in 34 LCL (11 PT, 19 bone metastases, 1 suprarenal mass, 1 axillary node, 2 supraclavicular nodes). A total of 11 patients displayed Tc-99m (V) DMSA uptake in LCL and one patient did not show uptake. In six patients, SPECT imaging showed deeply located PT in the lung parenchyma better than planar views. In five patients, both planar and SPECT views revealed peripherally located PT in the lungs. Early scans showed 18 LCL and late scans displayed all the LCL. Nine bone metastases on pre-TH Tc-99m (V) DMSA scans revealed matched areas of increased Tc-99m methylene diphosphonate (MDP) uptake on bone scans; six bone metastases were additionally detected on Tc-99m (V) DMSA scans when compared with bone scans, and four bone metastases on Tc-99m (V) DMSA scans could not be compared with bone scans because bone scan was not performed. In one patient, Tc-99m (V) DMSA scans became positive for bone metastases on post-TH later than the bone scans for some of the bone metastases. Neither planar nor SPECT imaging showed mediastinal lesions defined on thorax CT in nine patients. On TH monitoring, 17 LCL showed diminished Tc-99m (V) DMSA uptake, one disappeared, four were unchanged, three displayed increased uptake, and five new lesions were established. Of the six patients, TUR in PT increased in two (one survived), decreased in one (exitus), was unchanged in two (two exitus) on post-TH scans, and PT totally disappeared in one (survived) patient. Conclusions Tc-99m (V) DMSA scans are useful in detecting LCL, except for those around the blood pool regions, making it a promising modality to monitor TH response. Obtaining a single fifth hour late Tc-99m (V) DMSA scan is appropriate. SPECT should be applied to all patients for the detection of deeply located lesions.     

Clinical evaluation of 99mTc(V)-dimercapto succinic acid (DMSA) for imaging medullary carcinoma of thyroid and its metastasis

^99mTc(V)-DMSA kits developed by the Radiopharmaceutical Division, Bhabha Atomic Research Centre, have been evaluated for potential use in scanning medullary carcinoma of the thyroid and its metastases. There were 15 patients with proved medullary carcinoma and 6 patients with other differentiated thyroid carcinoma. Amongst the 15 patients with medullary carcinoma, 12(80%) showed positive localisation either in the primary or one or more metastatic sites. None of the six patients with carcinoma other than medullary showed increased concentration of ^99mTc (V)-DMSA. Of the 37 known metastatic sites in 15 patients with medullary carcinoma, 24 showed concentration of ^99mTc (V)-DMSA (64.9%). In addition, ^99mTc(V)-DMSA concentration was seen in 14 sites where no evidence of metastasis was revealed. The incidence of ^99mTc (V)-DMSA concentration in soft tissue and bone metastasis was similar.Isopharm, Radiopharmaceutical Division, BARC, Bombay-400 705, India     

99Tcm-MDP SPECT/CT骨显像在绝经后女性骨质疏松性胸腰椎椎体骨折中的增益价值

目的研究99Tcm-MDP SPECT/CT骨显像及其半定量分析指标在绝经后女性骨质疏松性胸腰椎椎体骨折中的增益价值。 方法回顾性分析2012年11月至2016年10月因轻微外伤或日常活动导致胸腰背部疼痛而就诊,最终诊断为骨质疏松性胸腰椎椎体压缩性骨折的绝经后女性患者81例。选取SPECT/CT矢状位融合断层图像,利用ROI技术重复勾画病灶椎体（T）及与其相邻的正常椎体（NT）,并计算病灶椎体与正常椎体的放射性计数比值,即T/NT值。将所收集病例根据椎体是否在99Tcm-MDP SPECT/CT骨显像后进行手术分成两组,一组为手术组,包括行经皮穿刺椎体成形术及椎体球囊后凸成形术的患者,另一组为非手术组。对两组T/NT值采用两独立样本t检验进行统计学分析。 结果（1）手术组共计110个椎体,T/NT值为2.44±0.84;非手术组共计70个椎体,T/NT值为1.04±0.14,两组T/NT值的差异有统计学意义（t=13.654,P < 0.05）。（2）发现椎体以外骨折,包括肋骨骨折29例、椎体附件骨折2例、骶骨骨折2例、耻骨骨折1例。 结论99Tcm-MDP SPECT/CT骨显像及其半定量分析指标在指导绝经后女性骨质疏松性胸腰椎椎体压缩性骨折临床治疗方案的选择和其他部位是否有骨折的诊断中具有一定的参考价值。     

99Tcm-DTPA-环九肽用于前列腺癌骨转移白细胞介素11受体显像的实验研究

目的 建立99Tcm标记白细胞介素11（IL11）类似物环九肽,即环状肽半胱氨酰-甘氨酰-精氨酰-精氨酰-丙氨酰-甘氨酰-甘氨酰-丝氨酰-半胱氨酸[c（CGRRAGGSC）]的方法,探讨标记物用于前列腺癌骨转移IL11受体（IL11R）显像的可行性.方法 采用间接法,用99Tcm标记c（CGRRAGGSC）制备99Tcm-DTPA-环九肽[99Tcm-DTPA-Bz-NH-SA-c（CGRRAGGSC）,简称99Tcm-DTPA-IL11RR].利用纸层析法及高效液相色谱（HPLC）测定标记率和稳定性.将99Tcm-DTPA-IL11RR（0.74 MBq/只）经正常ICR小鼠尾静脉注射后,观察其在小鼠体内生物学分布,计算血、脑、心、肝、脾、肺、肾、胃、小肠、肌肉、甲状腺、骨骼、胰腺每克组织百分注射剂量率（%ID/g）.γ显像动态（5只小鼠）观察99Tcm-DTPA-IL11RR在荷人PC-3前列腺癌骨转移瘤BALB/c裸鼠模型体内0.5,1,2,4,6,8和24 h表现,与99Tcm-亚甲基二膦酸盐（MDP）骨显像比较,采用感兴趣区（ROI）法计算99Tcm-DTPA-IL11RR显像肿瘤/对侧正常骨骼放射性（T/NT）比值,并用此2种显像剂进行裸鼠骨折模型显像比较.进行体内竞争抑制显像（3只荷瘤裸鼠）,观察标记物生物学活性.对计量资料数据行单因素方差分析.结果 99Tcm-DTPA-IL11RR标记率90.7%,HPLC即时测放化纯为（99.57±0.09）%,室温放置1,2,3,4,6,8和24 h,放化纯依序为（99.29±0.18）%,（98.95±0.78）%,（98.67±0.11）%,（96.53±0.91）%,（95.20±0.70）%,（88.38±0.22）%和（36.17±1.29）%.标记物经正常ICR小鼠尾静脉注射后主要经肾排泄,各时相重要组织脏器普遍摄取较低,肌肉和脑最低,4 h骨骼、肝摄取达峰值,分别为（1.910±0.109）和（0.366±0.030）%ID/g.注射后24 h体内放射性消失.模型鼠γ动态显像示脊柱骨髓、四肢关节髓腔轻度显影,体内放射性清除迅速;瘤灶放射性持续摄取,4 h最明显,延续至6～8 h;24 h全身影像极淡.以ROI法测量的模型鼠0.5,1,2,4,6,8和24 h T/NT比值分别为1.17±0.17,2.20±0.29,3.20±0.15,3.67±0.23,13.61±0.85,9.45±0.37和3.33±0.30（F=621.54,P＜0.05）.骨折模型99Tcm-MDP显像示骨折处放射性摄取,99Tcm-DTPA-IL11RR显像未见摄取.体内竞争抑制实验示环九肽对瘤体显像具有抑制作用.结论 99Tcm-DTPA-IL11RR标记率高,稳定性好,有望成为前列腺癌等富含IL11R的骨转移特异分子靶向显像剂.     

99Tcm-HMIBP的生物学特性及与99Tcm-MDP的骨显像比较

目的 通过99Tcm-1-羟基-2-(1-甲基咪唑-2-基)乙烷-1,1-二膦酸(HMIBP)和鲫99Tcm-亚甲基二膦酸盐(MDP)的骨显像质量比较,评价99Tcm-HMIBP作为骨显像剂的可能性.方法 制备HMIBP冻干药盒,对HMIBP及SnCl2-2H2O含量、放化纯、药盒pH值及在4℃下的稳定性等进行了研究.测定99Tcm-HMIBP在正辛醇/水相中的分配系数(P)及血浆蛋白结合率,计算血药清除动力学方程参数.同时研究了HMIBP的半数致死剂量(LD50).新西兰兔静脉注射99Tcm-HMIBP和99Tcm-MDP后同步显像比较.结果 99Tcm-HMIBP药盒含HMIBP 5 mg,SnCl2·2H2O 0.05 mg,药盒pH值为5,标记率和放化纯均为98%;在4℃下放置180 d后标记率为96%.在pH值为7.0和7.4时,P值分别为0.0125和0.0054,血浆蛋白结合率为44.77%.小鼠血药清除动力学方程为C=3.0979 e-0.0721t+0.1250 e-0.0076.HMIBP的LD50为8.2 mg/kg.兔骨显像表明,99Tcm-HMIBP和99Tcm-MDP在3 h时均可获得清晰的图像.结论 99Tcm-HMIBP生物学性能优良,显像效果与99Tcm-MDP相当,可能成为集显像与治疗于一体的骨显像剂.