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1.
<Superscript>68</Superscript>Ga-labelled DOTA-derivatised peptide ligands   总被引:4,自引:4,他引:0  
68Ge/68Ga generators provide cyclotron-independent access to positron emission tomography (PET) radiopharmaceuticals. We describe a system which allows the safe and efficient handling of 68Ge/68Ga generator eluates for labelling of DOTA-derivatised peptide ligands. The system comprises concentration and purification of the 68Ga eluate as well as labelling and purification steps for peptides, and can be used with different 68Ge/68Ga generator types. The suitability and efficiency were tested with two different DOTA-derivatised somatostatin derivatives and a DOTA-derivatised bombesin derivative. Amounts of 10–20 nmol of the peptides were sufficient and resulted in labelling yields of 50% for all peptides. The built-in safety precautions have proven to be appropriate in allowing use of the method for routine clinical applications. The system was set up and operated in a hot lab by personnel with no previous experience in the preparation of PET radiopharmaceuticals.  相似文献   

2.
Purpose Although positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) is a promising imaging modality for bone infections, the technique may still give false-positive results due to unspecific uptake in healing bone. This experimental study compared 18F-FDG and 68Ga in PET imaging of osteomyelitis and normal bone healing.Methods A diffuse osteomyelitis model of the tibia was applied in the rat (n=50). Two weeks after operation, PET imaging with 18F-FDG and 68Ga was performed, followed by peripheral quantitative computed tomography (pQCT) and radiography. Osteomyelitis was verified by quantitative bacteriology. In addition to in vivo imaging, ex vivo measurements of tissue radioactivity were performed to verify uptake of the tracers.Results Compared with controls with normal bone healing, the osteomyelitic tibias showed increased SUV ratios (i.e. radioactivity ratios between the operated and non-operated sides) for both 18F-FDG (1.74±0.37) and 68Ga (1.62±0.28) (P<0.001). Ex vivo measurements also showed increased tracer accumulation in the infected bone (P=0.003 for 18F-FDG and P<0.001 for 68Ga). The intensity of 68Ga uptake reflected pathological changes of osteomyelitic bones measured by pQCT. The uptake of 18F-FDG, however, did not show as close a correlation with the anatomical changes. The healing bones without infection exhibited slightly elevated uptake of 18F-FDG (SUV ratio 1.16±0.06), but 68Ga did not accumulate in the healing bone, as judged on the basis of both in vivo imaging (SUV ratio 1.02±0.05) and ex vivo measurements (SUV 0.92±0.21) (P=0.003 and P=0.022 compared with 18F-FDG uptake, respectively).Conclusion This study suggests the feasibility of 68Ga PET imaging of bone infections. However, further studies are needed to clarify the value of 68Ga PET for clinical purposes.  相似文献   

3.

Purpose

Development of a gallium-68-labeled renal tracer can be a good substitute for Tc-99m, a known SPECT tracer. In this study, effort was made to develop 68Ga-ethylenecysteamine cysteine (68Ga-ECC).

Methods

Ga-ECC was prepared using generator-based 68GaCl3 and ethylenecysteamine cysteine (ECC) at optimized conditions. Stability of the complex was checked in human serum followed by partition coefficient determination of the tracer. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min.

Results

Ga-ECC was prepared at optimized conditions in 15 min at 90 °C (radiochemical purity ≈97 ± 0.88 % ITLC, >99 % HPLC, specific activity: 210 ± 5 GBq/mM). 68Ga-ECC was a water-soluble complex based on partition coefficient data (log P; −1.378) and was stable in the presence of human serum for 2 h at 37 °C. The biodistribution of the tracer demonstrated high kidney excretion of the tracer in 10–20 min. The SUVmax ratios of the liver to left kidney were 0.38 and 0.39 for 30 and 90 min, respectively, indicating high kidney uptake.

Conclusion

Initial biodistribution results showed significant kidney and urinary excretion of the tracer comparable to that of the homologous 99mTc compound. The complex could be a possible PET kidney imaging agent with a fast imaging time.  相似文献   

4.

Introduction

68Ga is a positron-emitting nuclide that has significant imaging potential given that, unlike cyclotron-produced 18F, the isotope can be produced on-site utilizing a 68Ge/68Ga generator. We recently synthesized a novel bone-seeking agent by coupling a bisphosphonate with the 68Ga chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). This study presents a first report on the potential of this 68Ga bone-seeking radiopharmaceutical in the detection of bone metastases.

Methods

4-Amino-1-hydroxybutylidene-1,1-bisphosphonate was conjugated with 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]pentanedioic acid, yielding 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]-5-[(4-hydroxy-4,4-diphosphonobutyl)amino]-5-oxopentanoic acid (NOTA-BP). 68Ga-labeled NOTA-BP ([68Ga]NOTA-BP) was prepared by complexation of NOTA-BP with [68Ga] gallium chloride and evaluated in in vitro experiments, biodistribution experiments and micro-positron emission tomography (PET) imaging experiments.

Results

The labeling of NOTA-BP with 68Ga was completed by heating for 10 min. [68Ga]NOTA-BP was determined to have a radiochemical purity of over 95%, a high affinity for hydroxyapatite and a high stability in plasma. In in vivo biodistribution experiments, [68Ga]NOTA-BP demonstrated high bone uptake potential. Compared with 99mTc-labeled methylene diphosphonate ([99mTc]MDP) and [18F]fluoride, [68Ga]NOTA-BP exhibited faster blood clearance and a higher bone-to-blood ratio. In addition, mouse model bone metastasis was detected by micro-PET imaging at 1 h postinjection of [68Ga]NOTA-BP.

Conclusion

We have developed a novel 68Ga-radiolabeled bone-seeking agent. This [68Ga]NOTA-BP complex was found to have a high bone affinity and rapid blood clearance, and may thus prove to be useful as a bone-seeking agent for clinical PET.  相似文献   

5.
Summary Fifty-two patients with active brain tumors and 8 patients with brain lesions from surgical treatment and/or radio-and/or chemotherapy of their brain tumors were examined by positron emission tomography (PET) using (68Ga)-EDTA in addition to conventional X-ray computed tomography (XCT). All patients with active brain tumors showed abnormal uptake of radioactivity in the tumor region, while all treated patients had normal PET scans. Site and shape of abnormal radioactivity accumulation were in good agreement with the tumor as demonstrated by XCT. Small tumors had a tendency to appear larger in PET than in XCT, while tumors with a mean largest diameter of more than 50.7 mm in XCT usually appeared smaller in PET. Despite considerable overlap to tumor classes with respect to their degree of tracer uptake a highly significant decreasing order of tumor-sagittal sinus ratios of radioactivity (TSR) was found, malignant gliomas ranking highest (median TSR 0.634), followed by meningiomas (median TSR 0.522) and metastases (median TSR 0.391), benign gliomas showing the least uptake (median TSR 0.307). These findings suggest that PET with (68Ga)-EDTA has a high sensitivity supplementing XCT in the diagnosis of brain tumors, and may be helpful in early detection of recurrent tumor growth after therapy.  相似文献   

6.
Three 68Ge/68Ga generators have been evaluated over a period of 1 yr; the systems were compared with respect to 68Ga elution profiles and yields, parent 68Ge breakthrough levels, amounts of chemical contaminants present in the generator eluate, and the ease of 68Ga-radiopharmaceutical production. An ionic 68Ga/68Ga generator utilizing a tin dioxide column eluted with 1 M HCl was found to be the most suitable for preparation of 68Ga-labeled compounds for use in conjunction with positron emission tomography. Model studies suggest that the use of 68Ga for labeling limited amounts of a chelating group, such as proteins or antibodies attached to bifunctional chelates, may require preliminary purification of the radionuclide via extraction.  相似文献   

7.
A 70-year-old gentleman with a history of Gleason score 7 (3 + 4) prostate adenocarcinoma was treated with radical prostatectomy with clear surgical margins. Postoperatively his prostate specific antigen was undetectable. However, his prostate specific antigen was slowly rising and he was referred for a 68Galium-Prostate Specific Membrane Antigen (PSMA) PET/CT scan. Findings were suggestive of local prostatic cancer recurrence with no evidence of nodal or distant metastasis. An incidental PSMA avid focus was noted in the left frontal lobe, inseparable from the left frontal bone laterally. Subsequent MRI findings were consistent with meningioma. Meningioma is the most common primary brain tumor and may be a cause of false positive prostate cancer metastasis due to 68Ga-PSMA uptake.  相似文献   

8.
Although prostate cancer can metastasize to any part of the body, isolated testicular metastasis is very rare and only few cases have been reported so far. Here we present a case of 65-year-old male patient, known case of prostate adenocarcinoma, referred for 68Ga-PSMA PET/CT scan, post radiotherapy, and androgen deprivation therapy, for rising serum PSA levels. He was found to have an isolated testicular metastasis on the scan. This report highlights the importance of 68Ga-PSMA PET-CT scan in detecting these unusual and rare sites of metastasis from prostate cancer.  相似文献   

9.
Tumor-induced osteomalacia (TIO) is a rare disease that manifests with paraneoplasic syndrome and overproduction of fibroblast growth factor 23 (FGF23), leading to renal phosphate wasting and hyperphosphaturia, eventually leading to acquired hypophosphatemic osteomalacia. Diagnosis of this disease is often challenging because of the small size of the lesion, which can be localized in bone or soft tissue anywhere in the body. Detecting these occult mesenchymal tumors (OMT) is of great importance as they are potentially curable after tumor resection. The purpose of this case series is to provide some insight into the diagnosis and localization of OMT associated with osteomalacia, particularly using functional imaging with Ga68-DOTA peptide PET/CT scans.  相似文献   

10.
A method for producing carrier free 66Ga (T1/2:9.4h; +) by 4He bombardment of natural copper targets is presented. 66Ga is formed by means of the 63Cu (4He, n) 66Ga reaction. Production yields are given in the 17.5 to 8 MeV 4He energy range. Chemical purification of 66Ga from the copper target is described. The only radionuclidic impurity found in the final product was 67Ga. Albumin colloids from commercially available kits designed for use with 99mTc could easily be labeled with 66Ga and employed for studies of the lymphatic system by positron emission tomography.  相似文献   

11.
Objective68Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N, N′, N″-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68Ga-NGUL in healthy volunteers and the lesion detection rate of 68Ga-NGUL in patients with prostate cancer.Materials and MethodsWe designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68Ga-NGUL (2 MBq/kg; 96–165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared.ResultsAll 12 participants (six healthy adults aged 31–32 years and six prostate cancer patients aged 57–81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68Ga-NGUL PET/CT or conventional imaging. Among them, 68Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions.Conclusion68Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68Ga-NGUL is a valuable option for prostate cancer imaging.  相似文献   

12.
目的 评估68Ga-FAPI-04 PET/CT检查在肝胆肿瘤患者中的内照射剂量及生物分布。方法 本研究纳入因肝脏占位于北京协和医院接受PET/CT检查的6例患者,经静脉注射68Ga-FAPI-04(170.57 ±14.43) MBq后分别于第3、10、15、20、30和60 min进行全身显像。观察显像剂的生物分布;手动勾画感兴趣区;所有靶器官的内照射剂量应用OLINDA/EXM软件计算。结果 68Ga-FAPI-04在肝脏内放射性本底消退较快,在肿瘤组织内放射性摄取较为稳定,病灶平均SUVmax在注射后20 min达到最大(13.87 ±2.55);病灶平均靶本比逐渐升高,在注射后30 min达到最大(10.09 ±8.17)。1次68Ga-FAPI-04 PET/CT扫描的全身有效剂量为(0.020 ±0.002) mSv/MBq,吸收剂量最高的器官是膀胱壁,为(0.146 ±0.035) mSv/MBq。结论 68Ga-FAPI-04与18F-FDG全身有效剂量相近;肿瘤摄取快速,肝脏背景低,且不受血糖水平影响,有望成为潜在的肝胆肿瘤PET/CT显像药物。  相似文献   

13.
Purpose  The success of 68Ga-labeled peptides for positron emission tomography of neuroendocrine tumors is mainly depending on the complex chemistry of this radioisotope. 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), the chelator of choice has however limitations if its application is expanded to heat-sensitive proteins. Recombinant antibodies like single chain Fv or diabodies belong to this class of proteins. They are suited to provide imaging contrast despite the short-lived 68Ga because of their rapid blood clearances and nanomolar affinities. The heterobifunctional agent N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC) was chosen as an alternative ligand because this agent is complexing [68Ga]Ga3+ much faster than DOTA at ambient temperatures. Materials and methods  A versatile technology for HBED-CC conjugation of proteins and 68Ga-labeling has been developed. This included HBED-CC–tetrafluorophenol (TFP) ester synthesis, coupling to the antibody at various pH and complexation reactions performed in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer under different conditions. Results  The synthesis of the monoreactive 2,3,5,6-tetrafluorophenolate of HBED-CC at a carboxyl group not participating in complex formation used [Fe(HBED-CC)] for ester formation. The removal of Fe3+ from purified (HBED-CC)TFP ester was achieved with RP18 cartridge technology. The conjugation chemistry was performed with mAb425 which binds to the epidermal growth factor receptor (EGFR). This protein was used for optimizing purposes only. The influence of complexation parameters like temperature, pH, reaction time, and HBED-CC/antibody ratio on the biological activity of this model antibody was investigated. Furthermore, the outcome of this labeling procedure on the biological activity of a recombinant diabody (50 kDa) was studied. Conclusion  It is known that small HBED-CC/antibody ratios are prerequisites for minimal interference of labels with antigen-binding domains. Here, the coupling of about one HBED-CC per antibody proved to be sufficient for efficient 68Ga labeling, pointing to the successful application of 68Ga for molecular imaging with small recombinant proteins.  相似文献   

14.

Purpose

To evaluate the diagnostic performance of 68Ga-DOTATATE 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), 18F-FDG PET/CT and 131I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma.

Materials and Methods

Seventeen patients (male = 8, female = 9; age range, 13–68 years) with clinically proven or suspicious metastatic pheochromocytoma or paraganglioma were included in this prospective study. Twelve patients underwent all three modalities, whereas five patients underwent 68Ga-DOTATATE and 131I-MIBG without 18F-FDG. A composite reference standard derived from anatomical and functional imaging findings, along with histopathological information, was used to validate the findings. Results were analysed on a per-patient and on per-lesion basis. Sensitivity and accuracy were assessed using McNemar’s test.

Results

On a per-patient basis, 14/17 patients were detected in 68Ga-DOTATATE, 7/17 patients in 131I-MIBG, and 10/12 patients in 18F-FDG. The sensitivity and accuracy of 68Ga-DOTATATE, 131I-MIBG and 18F-FDG were (93.3 %, 94.1 %), (46.7 %, 52.9 %) and (90.9 %, 91.7 %) respectively. On a per-lesion basis, an overall of 472 positive lesions were detected; of which 432/472 were identified by 68Ga-DOTATATE, 74/472 by 131I-MIBG, and 154/300 (patient, n = 12) by 18F-FDG. The sensitivity and accuracy of 68Ga-DOTATATE, 131I-MIBG and 18F-FDG were (91.5 %, 92.6 % p < 0.0001), (15.7 %, 26.0 % p < 0.0001) and (51.3 %, 57.8 % p < 0.0001) respectively. Discordant lesions were demonstrated on 68Ga-DOTATATE, 131I-MIBG and 18F-FDG.

Conclusions

Ga-DOTATATE PET/CT shows high diagnostic accuracy than 131I-MIBG scintigraphy and 18F-FDG PET/ CT in mapping metastatic pheochromocytoma and paraganglioma.  相似文献   

15.
Purpose  In clinical routine somatostatin analogue positron emission tomography/computed tomography (PET/CT) such as 68Ga-DOTA-Tyr-octreotide (DOTATOC)-PET/CT could substitute conventional 111In-Octreotide scintigraphy. Immunohistochemistry (IHC) for somatostatin receptor 2 (SSTR2) might be a tool to predict positivity of 68Ga-DOTATOC in patients where initial staging was not performed, e.g., in incidental findings. We therefore compared a score of SSTR2-IHC with the in vivo standard uptake value (SUV) of preoperative or prebiopsy 68Ga-DOTATOC PET/CT. Materials and methods  In 18 patients, 68Ga-DOTATOC PET/CT scans were quantified with SUV calculations and correlated to a cell membrane-based SSTR2-IHC score (ranging from 0 to 3). Results  Negative IHC scores were consistent with SUV values below 10. Furthermore, all score 2 and 3 specimens corresponded with high SUV values (above 15). Conclusion  SSTR2-IHC scores correlated well with SUV values and we propose to use SSTR2 immunohistochemistry in patients missing a preoperative PET scan to indicate 68Ga-DOTATOC-PET/CT as method for restaging and follow-up in individual patients.  相似文献   

16.
The measurement of cerebral blood flow (CBF) by continuous C15O2 inhalation has only been validated previously by indirect experimental protocols. In the present study using baboons, these measurements were compared directly with those obtained by injection of 68Ga-labelled serum-albumin microspheres in the left cardiac ventricle. Using a modified labelling technique, no elution of 68Ga occurred in vivo. Both methods provided similar regional CBF values, which could be described by a significant linear correlation ( =0.82 CBFmicrospheres+5.7; P<0.001). The validity of the labelled-microsphere-injection method was verified. The feasibility of stable in vivo labelling of 68Ga to serum-albumin microspheres provides a reference method for organ blood-flow measurements using positron-emission tomography.  相似文献   

17.
PURPOSE: (18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. AIM: The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. MATERIALS AND METHODS: Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). RESULTS: The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. CONCLUSIONS: Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.  相似文献   

18.
A method for labeling monoclonal antimyosin antibodies with66Ga is described. The radionuclide is a positron emitter (t1/2: 9.4 h) produced by means of the63Cu (4He, n)66Ga reaction. Purification of the66Ga from the copper target is described in detail. Monoclonal antimyosin antibodies are labeled with66Ga at a high yield (99%) by transcomplexation from an acetate buffer with the diethylenetriamine pentaacetic acid (DTPA)-labeled antibody and preliminary evaluated in two dogs for imaging of myocardial necrosis by positron emission tomography.  相似文献   

19.
A 56-year-old man presented to the emergency department with shortness of breath during the COVID-19 pandemic. Chest computed tomography angiography (CTa) showed bilateral peripheral ground-glass opacifications classified as CO-RADS 5, but no pulmonary embolism. To analyze the possibility of CTa-undetectable pulmonary microthrombi and to rule out cardiac perfusion abnormalities, we decided to perform a rubidium-82 (82Rb) PET/CT. 82Rb PET/CT imaging in this patient yielded uptake in the pulmonary areas of ground-glass opacification and showed corresponding findings between 82Rb PET/CT and CTa imaging without any signs of microthrombi despite the elevated d-dimer. Even in the areas of profound groundglass opacifications, the increased 82Rb uptake indicates that perfusion is adequate to acquire 82Rb uptake in the pulmonary cells. 82Rb PET/CT is a promising imaging technique and might extend the diagnostic potential of conventional nuclear and radiological imaging in detecting pulmonary microthrombi or other minor perfusion defects.  相似文献   

20.
67Ga scintigrams in a patient with malignant lymphoma before and after chemotherapy are presented. 67Ga did not accumulate in the mostly necrotic mass with some viable cells. Negative uptake of 67Ga might reflect necrosis of the tumor; however, it is difficult to detect some residual tumor cells. Therefore, negative uptake of 67Ga in the mass seen in X-ray CT may not be totally reliable evidence of eradication of viable tumor cells.  相似文献   

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