Iranian Journal of Nuclear Medicine
Volume:23 Issue: 2, Summer-Autumn 2015

Knee joints are commonly involved with various inflammatory and non- inflammatory rheumatic diseases. Radiosynovectomy is being used as a local therapeutic option to alleviate pain and swelling in involved joints. The present study evaluated the effectiveness of radiosynovectomy for treatment of chronic knee synovitis. Through a search of Medline and SCOPUS with (Radiosynovectomy OR radio-synovectomy OR "radio synovectomy" OR "radiation synovectomy" OR radiosynoviorthesis OR radio-synoviorthesis OR synoviorthesis OR "radiochemical synovectomy" OR "radioisotope synovectomy") AND (Re-188 OR Y-90 OR Sm-153 OR P-32) as key words, 9 RCTs were enrolled in the analysis. The outcomes of interest were odds ratio and risk difference of improvement in the radiosynovectomy group compared to the control group. Odds ratio and risk difference for Sm-153 plus corticosteroid subgroup was 1.959[0.571-6.725, P=0.285] and 14.9% [-17.1%-47%, P=0.362] respectively. The subgroup of Y-90 plus corticosteroids showed pooled odds ratio and risk difference of 2.366[0.779-7.188, P=0.129] and 23.9% [-1.7%-49.4%, P=0.67] and in the subgroup Y-90 alone were 0.851[0.356-2.036, P=0.717] and -2.3% [-23.3%-18.7%, P=0.829], respectively. Combination of Y-90 colloid or Sm-153 with corticosteroids in radiosynovectomy have higher response rate compared to each of radioisotope or corticosteroid therapy alone.

Porphyrins are interesting derivatives with low toxicity, tumor avidity and rapid wash-out suggested as potential radiopharmaceuticals in radiolabeled form. In this work we report, synthesis, radiolabeling, quality control, stability, partition coefficient determination and biodistribution studies of 153Sm-5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (153Sm-4-MPP) in wild-type rats. [153Sm]-4MPP was prepared using [153Sm]SmCl3 and 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (H2-4MPP) for 18 h at 80-90°C. Stability of the complex was checked in final formulation and in presence of human serum for 24 h. The biodistribution of the labeled compound in vital organs of wild-type rats was studied. A detailed comparative pharmacokinetic study performed for 153Sm cation and [153Sm]-4-MPP up to 24h. The radiochemical purity of [153Sm]-4MPP was reported >97±2% and >99±0.5% by ITLC and HPLC, respectively. The specific activity was 220-230 MBq/mmol. The calculated partition coefficient for the compound was (log P=-1.09). The complex is mostly cleared from the circulation through kidneys and liver. The kidney:blood and kidney:muscle ratios 24 h post injection were 14.75 and 42.4, respectively. kidney/liver ratio was almost constant at all time intervals (0.6). [153Sm]-4MPP was prepared at the optimized conditions and suitable characteristics. Further investigations such as biological studies of this agent on tumor-bearing models are needed.

Differentiation between infection and sterile inflammation is one of the most difficult medical problems and is relevant in many clinical situations. Scintigraphy with radiolabeled antibiotics, еspecially labeled fluoroquinolones, is a promising tool for diagnosing bacterial inflammation. We have attempted to synthesize 99mTc-norfloxacin and studied its properties in experiment. In present study we labeled norfloxacin with 99mTc, determined its radiochemical purity by thin-layer chromatography procedure, compared the bactericidal activity of 99mTc-norfloxacin and unlabelled norfloxacin by disk diffusion, performed in vitro binding assays and evaluated the feasibility of 99mTc-norfloxacin to image soft-tissue infections in rat modal of thigh muscle infection. Scintigraphy was performed at 30 min, 90 min and 18 h post injection. Abscess –to–normal-site ratios were calculated. In this study 99mTc-norfloxacin with high radiochemical purity and low colloid content was synthesized. Disk diffusion method showed that 99mTc-norfloxacin retains bactericidal properties of unlabelled norfloxacin. In vitro binding studies demonstrated small degree of the tracer binding with S. aureus and ability of 99mTc-norfloxacin to bind with killed as well as alive bacteria. Uptake of the tracer was clearly visible in infected muscles and not visible in sterile inflammed muscles. The 99mTc-norfloxacin retains bactericidal properties of unlabelled norfloxacin. The tracer demonstrated small degree of S. aureus binding both with killed as well as alive bacteria. Studies which were performed in vivo in rats with a model of thigh muscle infection showed good ability of the radiopharmaceutical to image the infection.

Meningioma is usually a benign brain tumor, but sometimes with aggressive course. The aim of this study was to assess the ability of 201Tl Brain SPECT to differentiate the pathologic grade of meningioma preoperatively. Thirty lesions in 28 patients were evaluated in this study. Early (20 minutes) and late (3 hours) brain SPECT images were performed and early uptake ratio (EUR), late uptake ratio (LUR) and retention index (RI) were calculated. All patients were operated and pathologic grade of tumors were defined according to World Health Organization grading system. SPECT results were compared in different pathologic groups. Data analysis clarified no significant difference of EUR in benign and aggressive meningioma (P=0.2). However LUR and RI were significantly higher in aggressive tumors (P=0.001 and P=0.02, respectively). According to our data Tl-201 Brain SPECT with early and late imaging has 80% sensitivity and specificity to differentiate malignant from benign meningioma.

The relation between patient Body Mass Index (BMI) and the external dose rate of thyroid cancer patients treated with 131I has been investigated. A total of 183 patients treated with 131I were selected randomly and divided according to their administrated activity into three groups: 3.7GBq, 5.5GBq and 7.4GBq. They were also stratified into three groups according to their BMI values namely normal, overweight and obesity. A telescopic radiation survey meter was used to measure the dose rate at 1 meter from patient neck level. The measurement was effectuated after 1, 24 and 48 hours post dose administration. Our findings showed that regardless the patient sex, age, and administrated dose, the external dose rate values in normal BMI range patient group were higher by 11% (as an average) as compared to overweight and obesity groups when the dose administrated was 150 and 200 mCi while it was higher by 49% for patient received 100 mCi. The BMI patient value may be taken into account in the radiation protection optimization process by the physicist during isolation period and general public after patient discharge.

This study was launched to evaluate the sensitivity and specificity of 99mTc-Ciprofloxacin to distinguish infection foci induced by staphylococcus aureus and inflammation lesions induced by carrageenan in the rat foot in comparison with 67Ga-Citrate scintigraphy. The labeling and quality control of 99mTc-Ciprofloxacin kits have been performed according to the manufacturer’s instructions. A total number of 40 adult, male NMRI rats were randomly divided into two equal groups, one group for 99mTc-Ciprofloxacin and the other group for 67Ga-Citrate scintigraphy. Every group was subdivided into two groups equally. Septic lesion was induced by Staphylococcus aureus. Aseptic inflammation lesion was induced by carrageenan in the rat foot in the other group. The 99mTc-Ciprofloxacin and 67Ga-Citrate scintigraphy studies have been performed to evaluate the efficacy of radiotracers. The images showed 67Ga uptake at the infection and inflammation sites. The infection foci could be visualized by 99mTc-Ciprofloxacin scintigraphy due to selective binding of ciprofloxacin to DNA gyrase of bacteria. The inflammation sites have been observed by non-specific uptake of 99mTc-Ciprofloxacin. None of both imaging studies have shown preferentially diagnosis of septic and aseptic inflammation lesions. The sensitivity, specificity and positive predictive value of both scintigraphic techniques were 100%, 50% and 50%, respectively. The 99mTc-Ciprofloxacin scintigraphy is sensitive for visualization of the lesion, but it could to discriminate between septic and aseptic inflammation lesions. Other modalities must be considered for interpretation of images obtained by 99mTc-Ciprofloxacin scintigraphy.

The gastrin releasing peptide (GRP) receptor is over expressed 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. 99mTc-bombesin scans were performed in 21 patients (45±21years) with breast tumor. Post-injection of 555-740 MBq 99mTc-bombesin, the dynamic imaging of the chest with 60 seconds for each frame up to 20 minutes was acquired. Subsequently, 360◦ image SPECTs of the chest was performed in 120 steps, 20 seconds per projection. In addition, whole-body anterior and posterior views were obtained 60 and 180 min after injection. Definite diagnosis was based on excisional biopsy and histopathological examination. 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. Our data suggest that this new 99mTc-bombesin analog could be useful in SPECT imaging of primary breast cancer.

Bone pain palliation therapy is a mandate in handling end-stage cancer patients. The development of new ligands with higher stability, better pharmacokinetics and lower unwanted tissue uptakes (liver and GI) is still ongoing. In this work Lu-177 labeled (3-amino-1-hydroxypropane-1, 1-di-yl) -bis- (phosphonate) (177Lu-pamidronate; 177Lu-PAM), and (3-amino-1-hydroxybutane-1, 1-di-yl) -bis- (phosphonate) (177Lu-alendronate; 177Lu-ALN) complexes were prepared successfully using related ligands and 177LuCl3 at 25ºC & 60ºC at various ligand: metal ratios for 60-360 min. Lu-177 chloride was obtained by thermal neutron irradiation (4 × 1013 n. cm-2s-1) of natural Lu2O3 samples. Radiochemical purities of 177Lu- complexes were checked by ITLC and HPLC. Stability studies of final preparation in the presence of human serum were evaluated along with protein binding studies as well as hydroxyapatite (HA) binding test. The biodistribution of 177Lu-complexes and 177LuCl3 in mice were determined for 7 d. The complexes were obtained in high radiochemical purity ITLC (>97%) and HPLC (>99. 9%). Satisfactory stability in presence of human serum and final formulations were obtained (»90% in 48 h). HA binding assay demonstrated >98% binding from 5-20 mg. The complex protein binding was about 50-58%. Biodistribution of both complexes demonstrated low bone uptake ratios at all time intervals, for far inferior to 177Lu-EDTMP.

We aimed to assess whether the vasodilator effect of oral dipyridamole on the left ventricular systolic function in patients with suspected CAD is different from that of intravenous (IV) dipyridamole using Tc-99m MIBI myocardial perfusion gated SPECT. Eighty-nine patients (17 M / 72 W; 61 ± 10 years) were enrolled in this study. The patients underwent a dipyridamole stress test for the gating study. Forty-one patients were given oral dipyridamole (OD), and 48 patients were given intravenous dipyridamole (ID). Each group was divided into two subgroups according to whether they had normal or abnormal myocardial perfusion scintigraphy (MPS) findings (reversible perfusion defect). A two-day dipyridamole pharmacologic stress-rest Tc-99m MIBI myocardial perfusion gated SPECT protocol was performed in all patients. The LV ejection fraction (EF), end diastolic volume (EDV) and end systolic volume (ESV) were calculated from the gated data. In the ID group, LV myocardial perfusion was normal in 28 cases and abnormal in 20 cases. In abnormal ID cases, a significant difference between rest and stress EDV was detected (P = 0.017). In the OD group, the LV myocardial perfusion was normal in 20 and abnormal in 21 cases. In the OD normal cases, the rest EF (P = 0.012) and EDV (P = 0.029) were significantly different from the stress cases. The effect of ID test continues during gated SPECT and results in LV diastolic dysfunction in patients with abnormal myocardial perfusion. Oral administration is also highly effective for detecting real myocardial ischemia that causes LV systolic and diastolic dysfunction.

The classical triad of McCune-Albright syndrome (MAS) consists of polyostotic fibrous dysplasia (FD), skin hyperpigmentation (café-au-lait spots), and endocrine dysfunction, frequently seen in females as precocious puberty. Etiology is genetically based and is explained by mosaicism of activating somatic mutations of the alpha-subunit of Gs protein. Clinical presentation is varied and is dependent on the particular distribution of affected cells, causing a broad spectrum of endocrine and non-endocrine manifestations. Typical endocrinopathies are precocious puberty, hyperthyroidism, growth hormone excess, hyperprolactemia, and hypercortisolism. Manifestations usually occur during infancy and childhood. We present 2 classical cases of MAS with rare association of cerebral and endocrine dysfunction (unilateral Graves’ disease with contralateral thyroid hemi agenesis). The first case is an adult onset MAS with hyperparathyroidism and schizophrenia; this association is hitherto unreported in literature. Literature search showed that mutations in the Gsα gene may be associated with the pathogenesis of schizophrenia which is similar to the underlying factor in MAS. The second is a child exhibiting classical MAS with hyperthyroidism (unilateral Grave's disease) which is common but is associated contralateral thyroid hemiagenesis.

Gliomas account for almost 80% of primary malignant brain tumors in adults. Magnetic Resonance imaging (MRI) is still the gold standard for diagnosis of brain tumors and brain 99mTc-tetrofosmin Single Photon Emission Computed Tomography (99mTc-tetrofosmin-SPECT) has been established as a useful tool for their evaluation. Fluorine-18–2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) provides non-invasive information for staging, clinical assessment and prognosis of glial tumors. We report 2 cases of patients with brain lesions described on MRI suspected for malignancy, however 99mTc-tetrofosmin-SPECT that didn’t show any lesion, 18F-FDG PET/CT revealed radiotracer uptake that supported the hypothesis of malignant gliomas, confirmed later by biopsy. Our cases confirm 18F-FDG PET/CTmay be useful for differentiating common enhancing malignant brain tumors and is recommended when differential diagnoses are difficult to narrow using MRI and 99mTc-tetrofosmin-SPECT. 18F-FDG PET/CT can be used to characterize their aggressiveness and to detect a more feasible site for a stereotaxic biopsy. It yields supplementary non-invasive information to conventional imaging useful in the clinical decision-making.

Osteitis fibrosa cystica is the classic patognomonic form of skeletal disease in hyperparathyroidism that characterizes with decreased cortical bone thickness compared to increased cancellous bone. We present a case of 52-year old female patient with osteolysis of the left calf on radiographic images. The bone scan detected multiple focal pathological accumulations in the skull, left tibia, both femurs and in the left ischium. The scan was indicative of secondary multiple skeletal metastases. Because the patient had no previous history of primary malignant disease, metabolic bone disease was suspected and also confirmed after i.v application of 99mTc-MIBI. The scan was in favor of parathyroid adenoma with bone complication (osteitis fibrosa cystica). Neck ultrasonography revealed hypoechoic oval mass below the left lower thyroid lobe that suggested the possibility of parathyroid adenoma. An increased ionized calcium level and PTH confirmed the diagnosis of primary hyperparathyroidism. Parathyroidectomy with radioguided surgery was performed. Hyperparathyroidism is a curable disease and a clinician should always bear in mind a metabolic bone disease when performing a nuclear bone scan where multiple bone lesions are detected (a hallmark of metastatic disease).