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Evaluation of 188Re-HEDP efficacy in metastatic bone pain palliation therapy
Davood Beiki1, Babak Fallahi1, Maryam Tajik1, Peiman Haddad2, Amir Mohammad Arefpour2, Hamidreza Mirzaei3, Armaghan Fard-Esfahani1, Alireza Emami-Ardekani1, Mohammad Eftekhari1
1Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran
2Department of Radiation Oncology, Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Iran
3Radiation Oncology Department, Cancer Research Center, Shohada-e-Tajrish Hospital, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
Objective: Bone metastases are the most common cause of cancer-related pain in various primary malignant tumors, most often, breast and prostate. 188Re-hydroxyethylidene diphosphonate (188Re-HEDP) is a new and less expensive bone seeking radiopharmaceutical with favorable physical characteristics of the radionuclide such as short half life of 16.9h, maximal β energy of 2.1 MeV with a 15% γ-component of 155 keV and easily available from an in-house 188W/188Re generator. The aim of this study is to evaluate the therapeutic efficacy and safety profile of bone palliative therapy following administration of 188Re-HEDP.
Materials and Methods: Seventeen patients (7 men, 10 women; mean age, 57.1±13.3 years) with painful metastatic bone lesions were included in the study. Before and after treatment with 1 mCi/kg of 188Re-HEDP, the patients were followed at weekly intervals for the first months and every two weeks thereafter for as long as four months using standardized sets of questions including Karnofsky index and ECOG (Eastern Cooperative Oncology Group) performance status. Hematologic profiles were recorded before therapy and weekly for 8 weeks after treatment.
Results: Significant pain relief was found in 68.8% of our patients. Decreased from 8.34±2.10 to 5.55±2.45 at visual analogue scale was observed 4 weeks after the treatment. The osteoblastic lesions (breast and prostate) showed rather similar response to the treatment. Mean platelet counts decreased in 6th week and returned to baseline level in 8th week. Mean leukocyte counts in 6th week were lower than baseline (4913±2210/ml vs. 6502±2410/ml; p=0.02) and one patient showed grade III leukopenia without any serious complication.
Conclusions: 188Re-HEDP is an effective radiopharmaceutical in metastatic bone pain palliation. Side effects include mild and transient thrombocytopenia and leucopenia and no life threatening side effect is observed.
Synthesis and preliminary evaluation of a new 99mTc labeled substance P analogue as a potential tumor imaging agent
Davood Beiki1, Mostafa Erfani2, Saeed Mozaffari1, Fariba Johari Daha2,
Farzad Kobarfard3, Saeed Balalaie4, Babak Fallahi1
1Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran 2Nuclear Science Research School, Nuclear Science and Technology Research Institute (NSTRI), Atomic Energy Organization of Iran (AEOI), Tehran, Iran
3Department of Medicinal Chemistry, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
4Peptide Chemistry Research Center, K. N. Toosi University of Technology, Tehran, Iran
Objective: Neurokinin 1 receptors (NK1R) are overexpressed on several types of important human cancer cells. Substance P (SP) is the most specific endogenous ligand known for NK1Rs. Accordingly, a new SP analogue was synthesized and evaluated for detection of NK1R positive tumors.
Materials and Methods: [6-hydrazinopyridine-3-carboxylic acid (HYNIC)-Tyr8-Met(O)11-SP] was synthesized and radiolabeled with 99mTc using ethylenediamine-N,N'-diacetic acid (EDDA) and Tricine as coligands. Common physicochemichal properties of radioconjugate were studied and in vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. In vivo biodistribution in normal mice and in tumor bearing nude mice bearing tumor xenografts was also assessed.
Results: The cold peptide was prepared in high purity (>99%) and radiolabeled with 99mTc at high specific activities (84-112GBq/µmol) with an acceptable labeling yield (>95%). The radioconjugate was stable in vitro in the presence of human serum and showed 44% protein binding to human serum albumin. In vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 ± 0.22 % with the ratio of 60.21 ± 1.19 % for its specific fraction and increasing specific internalization during 4h. Receptor binding assays on U373MG cells indicated a mean Kd of 2.46 ± 0.43 nM and Bmax of 14325 ± 904 DPM/8×105cells 128925 ± 8145 sites/cell. In vivo investigations determined the specific tumor uptake in 3.36 percent of injected dose per gram (%ID/g) for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated.
Conclusions: This new radiolabeled peptide could be a promising radiotracer for detection of NK1R positive primary or secondary tumors.
Evaluation of a new 99mTc-Bombesin analog in differentiation of malignant from benign breast tumors
Davood Beiki1, Babak Fallahi1, Fatemeh Karami1, Ahmad Kaviani2, Iraj Harirchi2, Ramesh Omranipour2, Mostafa Erfani3, Saeed Farzanefar1, Armaghan Fard-Esfahani1, Alireza Emami-Ardekani1, Mohsen Saghari1, Mohammad Eftekhari1
1Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran
2Department of Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
3 Nuclear Science and Technology Research Institute, Atomic Energy Organization of Iran (AEOI), Tehran, Iran
Objective: The gastrin releasing peptide receptor (GRPR) is overexpressed in a variety of common human tumors. Radiolabeled bombesin analogues have exhibited high binding affinity for these receptors. The aim of this study was to assess the value of a new 99mTc-bombesin analog in the differentiation of malignant from benign breast tumors.
Materials and Methods: 99mTc-bombesin scans were performed in 17 patients with breast tumor. Post-injection of 20 mCi 99mTc-bombesin, planar dynamic images of chest were acquired. SPECT/CT images of the chest were also obtained. Subsequently, whole-body planar scans were carried out by one- and four hours of radiotracer injection. Definite diagnosis was based on excisional biopsy and histopathological examination.
Results: Thirteen patients demonstrated breast carcinoma and 8 patients were diagnosed as benign lesions. 11 out of 13 patients with breast carcinoma showed radiotracer uptake in the breast lesion. Nine out of 13 patients with breast carcinoma showed axillary lymph node involvement from which only two revealed radiotracer accumulation in the axillary lesion. All patients with benign lesions revealed negative scan. Delayed planar whole body images showed no additional diagnostic information in comparison to one-hour images. The sensitivity, specificity, PPV and NPV of 99mTc-bombesin scan were 84.6%, 100%, 100% and 80%, respectively.
Conclusions: Our data suggest that 99mTc-bombesin SPECT imaging could be useful in detection of primary breast cancer.
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