Radioisotope synovectomy with rhenium186 in haemophilic synovitis for elbows, ankles and shoulders.

We have performed 221 radioisotope synovectomy (RS) in more than 150 children and young adults with haemophilia, age ranging 3-30 years (mean 15) in Ege Hemophilia Center, Izmir, Turkey for last 7 years. We always preferred to use Yttrium 90 (Y(90)) for knees; however, since 2005, we started using rhenium 186 (Re(186)) for medium-sized joints with respect to safety. In this article, we have evaluated long-term experience ranging from 6 months to 3 years (mean 18 months) with Re(186) for elbows (n = 35), ankles (n = 26) and shoulders (n = 2) in total of 63 RS procedures for 49 patients. Their age range was 3-30 years and mean age was 15.5. Two mCi of Re(186) intra-articularly injected for treating target joints and chronical synovitis. After RS, joint bleedings were decreased for all patients. The best results were obtained for all joints in patients with grade-II synovitis as like earlier experience with Y(90). Excellent rates (no bleeding) were observed in grade-II synovitis in 81% and 46% for elbows vs. 86% and 57% for ankles after 6 months and after 1 year follow-up of patients, respectively. In grade-III synovitis, excellent rates were 53% and 25% for elbows and 44% and 29% for ankles, respectively. In five joints for five patients, repeated injections were needed for better outcome. No adverse events such as radioisotope leakage, local inflamatory reactions or malignancy development were observed during and after RS. For medium-sized joints, RS with Re(186) seems to be either effective or safe treatment method. Our results confirm those previously published by others on the value of Re(186) synoviorthesis in medium-sized joints in haemophilia patients. After this experience, we changed our protocol and we use Re(186) for all medium-sized joints for treating chronical synovitis.

Integrated PET/CT for the evaluation of para-aortic nodal metastasis in locally advanced cervical cancer patients with negative conventional CT findings.

OBJECTIVE: The aim of this study was to evaluate the usefulness of integrated 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) for the detection of para-aortic nodal status and to test whether PET/CT change management strategy in locally advanced cervical cancer (LACC) patients with negative conventional CT findings. MATERIALS AND METHODS: Sixteen locally advanced (FIGO stage IIB-IVA) cervical squamous cancer patients with negative conventional CT findings were eligible to enter this prospective study. All patients underwent firstly PET/CT scans then extraperitoneal surgical exploration for para-aortic lymphadenectomy. Based on histopathologic confirmation, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the PET/CT for para-aortic lymph node metastasis were estimated. RESULTS: The median age was 48.7 (range 42-67). The accuracy, sensitivity, specificity, PPV and NPV of the PET/CT were 75%, 50%, 83.3%, 50% and 83.3%, respectively. The treatment was modified in four of sixteen (25%) patients; four patients received EFRT in combination with cisplatin chemotherapy instead of standard pelvic field radiotherapy in combination with cisplatin chemotherapy. CONCLUSION: Our results, despite our study group is small, suggest that PET/CT is an effective imaging technique in the evaluation of LACC with negative CT findings. It may help planning the management especially selecting radiation field. However, larger controlled studies are needed to recommend PET/CT as an alternative to pre-treatment surgical staging.

Long-term evaluation of radioisotope synovectomy with Yttrium 90 for chronic synovitis in Turkish haemophiliacs: Izmir experience.

Since 2001 we have performed 105 radioisotope synovectomy (RS) in 65 children and young adults, age ranging from 3 to 25 years with a average of 15 years in Ege University Hospital, Izmir, Turkey. One fourth of cases were below 10 years of age. All patients had severe haemophilia A and B. Ten patients (17 joints) had high responder inhibitor. We prefer to use Yttrium 90 for all joints (5 mCi for knees; 2 mCi for others). The knees were injected in 56 cases, elbows in 24 cases, ankles in 23 cases and shoulders in two cases. Steroid injections were not preferred as the principle drug of choice. Mean follow-up period after procedure was 2 years (range: 6 months to 3.5 years). All inhibitor patients had satisfactory results. The best results were obtained in elbows than knees and ankles. Excellent rates (no bleeding) were observed in grade-II synovitis 84% for knees, 93% for elbows and 50% for ankles. Because of the excellent and good response (bleeding reduction to 75%), rates were 100% for knees and elbows and 92% for ankles. In six cases, repeated injections were given at 6-month interval and all of them had good results. The grading of synovitis seems to be an important parameter than the age of the patient. Even in patients below 10 years of age, outcomes are not satisfactory in all joints with grade-III vs. grade-II synovitis (12% vs. 73%). No serious complications were observed during and after procedure except two cases. A mild and transient inflammatory reaction was observed in the ankle. There was a minimal radioisotope leakage to superficial skin in the elbow. RS seems to be a safe and effective treatment for chronic synovitis causing recurrent joint bleedings.

Self-radioiodination of iodogen.

Iodogen (1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglucoluril) is commonly used for the radioiodination of proteins as an oxidative agent. The oxidative character of iodogen is not clear, but the two carbonyl groups in its structure probably have an essential role in its oxidizing character. In this study, the self-radioiodination of iodogen has been examined. It was observed that about 10-20% of the initial iodine radioactivity was consumed for the self-radioiodination of iodogen itself. On the other hand, the radioiodinated iodogen removed by ethyl alcohol from the iodogen-coated tubes showed clearly that no thyroid uptake was observed and that it was rapidly cleared out from the whole body of a rabbit administered with the radioiodinated iodogen by injection via the ear vein.

Labeling of penicillamine di sulfide with technetium-99m.

Complex forming conditions of Penicillamine di sulfide with 99mTc have been specified. Labeling of penicillamine di sulfide with 99mTc by direct reduction with SnCl2 did not give favorable good results while the 99mTc complex of penicillamine can be easily obtained. Ligand exchange reaction with 99mTc-gluconate was attempted and a 95% labeling efficiency was obtained. Radiopharmaceutical potential of 99mTc-PADS (99mTc-Penicillamine di sulfide) has been investigated with a gamma camera in rabbits and the complex was found to be uptaken mostly by the liver and kidneys.

The role of 99Tcm-tetrofosmin myocardial perfusion scintigraphy in the assessment of patients with previous myocardial infarction: a comparative study with 201Tl.

The aim of this study was to determine the utility of 99Tcm-tetrofosmin cardiac imaging in patients with previous myocardial infarction and with significant coronary artery disease (CAD) compared with that of 201Tl cardiac imaging. Sixteen patients (14 males, 2 females) were studied by same-day exercise-rest 99Tcm-tetrofosmin imaging and exercise, rest and reinjection 201Tl cardiac imaging. For each study, semi-quantitative visual analysis was performed in 20 segments using a 4-point scale. The regional distribution and defect reversibility with the two tracers were compared with the results of coronary angiography. A total of 320 segments were analysed. There was a statistically significant concordance between the numbers of fixed and reversible segments in both studies in myocardial segments supplied by totally occluded coronary arteries (Group 1), as well as in segments supplied by significantly stenosed coronary vessels (Group 2). The exercise and rest uptake of both 99Tcm-tetrofosmin and 201Tl in myocardial segments supplied by totally occluded coronary arteries with poor collateral flow was significantly lower compared with segments supplied by totally occluded coronary arteries with efficient collateral flow (P < or = 0.05). When the uptake of both tracers was analysed according to each major vascular territory, the mean exercise and rest uptake grades of 99Tcm-tetrofosmin and 201Tl were similar. There was also no significant difference in defect reversibility between the two tracers. Discordant results were observed in the territory of the right coronary artery in Group 1 (mean exercise grade of 99Tcm-tetrofosmin = 2.26 +/- 0.7 and of 201Tl = 1.92 +/- 0.8; P < or = 0.001) and in Group 2 (mean grade of 99Tcm-tetrofosmin = 0.79 +/- 0.65 and of 201Tl = 0.95 +/- 0.65; P < or = 0.05). The results of the present study indicate that the overall diagnostic utility of 99Tcm-tetrofosmin in the identification of individual stenosed vessels is comparable with 201Tl in both patients with totally occluded coronary arteries and those with significantly stenosed vessels. The regional distribution of both tracers was lower in myocardial segments supplied by totally occluded coronary arteries with poor collateral flow.

Detection of metastatic bone lesions in patients with prostate carcinoma: 99Tcm-monoclonal antibody imaging.

Bone scintigraphy has been shown to be sensitive in determining bone involvement in patients with malignancy, but it does not allow the assessment of bone marrow lesions in early disease. The aim of this study was to detect bone marrow invasion using 99Tcm-labelled monoclonal antigranulocyte antibody (AgMoAb) in patients with prostate carcinoma. We studied 56 patients whose mean (+/- S.D.) age was 67 +/- 7 years. The mean prostate-specific antigen level was 6.1 ng ml-1 (normal range 0-5 ng ml-1). Twelve patients were in stage A, 16 in stage B, 17 in stage C and 11 in stage D. Six patients had been receiving chemotherapy and four patients radiotherapy before scanning. Bone scans were obtained 2 h after the intravenous injection of 555 MBq 99Tcm-methylene diphosphonate (99Tcm-MDP). Within a week, bone marrow imaging was performed 4 and 24 h after the injection of 555 MBq 99Tcm-AgMoAb. Metastatic bone lesions were detected on the 99Tcm-MDP scans of 14/56 (25%) patients, of whom one was in stage A, two in stage B, four in stage C and seven in stage D. Hypoactive lesions in bone marrow were detected in 25/56 (45%) patients, of whom two were in stage A, five in stage B, seven in stage C and 11 in stage D. Bone marrow metastases were confirmed in six patients by computed tomography (CT) and magnetic resonance imaging (MRI) and in two patients by marrow aspiration biopsy. A false-positive immune scintigram was found in three patients previously receiving radiotherapy or chemotherapy. We suggest that 99Tcm-AgMoAb scintigraphy is a sensitive procedure for the detection of bone marrow lesions. However, the reason for false-positive and false-negative results should be considered and CT, MRI and marrow biopsy should be performed when clinically necessary.

Synthesis and iodine-125 labelling of glucuronide compounds for combined chemo- and radiotherapy of cancer.

Some types of cancer cells have high levels of beta-glucuronidase activity. This enzyme is able to deglucuronidate a variety of glucuronide derivatives on the cell membrane. Either O- or N-glucuronides can be selectively incorporated into the cancer cells. If the aglycone is cytotoxic, the glucuronide can potentially be used as a selective anti-cancer drug in cancers with high levels of beta-glucuronidase activity. Nevertheless, in vitro studies carried out by various investigators have shown that the cytotoxicities of several glucuronides in cancer cells are not sufficiently high for their use as effective anti-cancer drugs. For this reason, we have synthesized glucuronide compounds radiolabelled with iodine-125 combining the radiotoxicity of this Auger electron emitter with the chemotoxicity of the aglycone portion of the glucuronide.

Acute alternating hemiplegia. A case report.

Acute alternating hemiplegia in childhood is a rare disorder characterized by onset before 18 months of age and frequent attacks of alternating paralysis. In this case report, a 20-month-old boy having the diagnosis of acute alternating hemiplegia is presented. The diagnosis was based on clinical features. The frequency and severity of the hemiplegic attacks decreased following flunarizine therapy. In this case, cerebral perfusion was investigated during ictal and interictal periods. Tc-99m HMPAO-Brain single photon emission computed tomography (SPECT) revealed normal cerebral perfusion in ictal periods and hypoperfusion in interictal periods.

Is 201Tl a reliable agent in tumour imaging?

Thallium-201 (201Tl) imaging has been widely used to differentiate post-therapy reactions from residual viable tumour or local recurrence. However, the ability of 201Tl to discriminate between tumour and post-therapy changes with superimposed infection/inflammation is unclear. This experimental study investigated the localization of 201Tl in infected/inflamed tissues. Twenty-four rats infected with Staphylococcus aureus and 10 rats injected with a standard volume of saline solution (SS) into the thigh muscles were studied. Twenty-four ours after microorganism or SS administration, 18 MBq 201Tl was injected intravenously. Images were recorded at 20 min and 3 h post-injection. The increased tracer uptake was evaluated qualitatively and quantitatively by calculating the ratios (L/C) derived from regions of interest drawn over the lesion and the contralateral thigh muscle. After the imaging procedure, histopathological examination was also performed. Whereas the control group showed no abnormal accumulation of activity, the infected rats demonstrated markedly increased activity, especially on the 20 min images. The mean L/C ratios for the 20 min and 3 h images for the infected rats were 2.18 +/- 0.20 and 1.52 +/- 0.04, respectively (P < 0.0005). In conclusion, positive uptake due to an infective process may limit the use of 201Tl in studies monitoring response to tumour therapy. Although delayed imaging may help to overcome this limitation, further investigations among a large series of patients are required in order to improve the reliability of 201Tl imaging in oncology.

Accumulation of 99Tcm-polyclonal immunoglobulin in different stages of infection: an experimental study.

In this experimental study, the utility of 99Tc(m)-polyclonal human immunoglobulin (99Tcm-HIG) for localizing acute and chronic phases of inflammatory lesions was investigated. Three groups of rats were inoculated with Staphylococcus aureus in the right thigh. Then, 24 h (group I, n = 12), 48 h (group II, n = 12) and 72 h (group III, n = 12) post-inoculation, the rats received 40 MBq 99Tcm-HIG into the jugular vein. In addition, two control rats were studied at 24 h after inoculation of sterile saline. Both visual and quantitative evaluations were undertaken. The acute and chronic stages of inflammation were determined by pathological examination. The mean ( +/- S.D.) lesion/contralateral uptake ratios at 4 and 24 h after 99Tcm-HIG injection were: group I, 1.22 +/- 0.1 and 2.12 +/- 0.16; group II, 1.15 +/- 0.08 and 2.25 +/- 0.16; group III, 1.06 +/- 0.09 and 2.08 +/- 0.14. In conclusion, the acute and chronic phases of infection showed non-significant differences in 99Tcm-HIG uptake ratios.

Cerebellar mutism: report of seven cases and review of the literature.

It is well known that degenerative disease, hemorrhage, infection, and neoplastic disease of the cerebellum can lead to speech disorder. Mutism after posterior cranial fossa surgery was first reported by Rekate et al. and Yonemasu in 1985. We review and analyze the cases of cerebellar mutism that are reported in the literature that is available in English. We found 39 reported cases that included details regarding mutism. We review and analyze a total of 46 cases, including those of our seven patients. The ages of the patient ranged from 2 to 61 years (mean, 10.4 yr). Ninety-one percent of the patients were children. The vermis was the site of the mass lesions in > 90% of the cases. The pathological findings of the lesions were as follows: 33 medulloblastomas, 7 astrocytomas, 4 ependymomas, 1 metastatic tumor, and 1 arteriovenous malformation. All mass lesions were considered to be large or very large. The latency for the development of mutism ranged from 0 to 6 days (mean, 1.7 d). The mutism lasted from 4 days to 4 months (mean, 6.8 wk). Dysarthric speech ensued after the mutism was resolved in 35 of 46 patients. Mutism was transient in all of the cases. Cerebellar mutism is a transient complication of posterior fossa surgery for midline mass lesions.

Clinical evaluation of metastases of malignant melanoma imaging with 99Tcm-glutathione and 99Tcm-anti-melanoma antibody: a comparative study.

The aim of this investigation was to test for the scintigraphic detection of metastases of malignant melanoma with a new radiopharmaceutical, 99Tcm-glutathione (99Tcm-GSH), in comparison with 99Tcm-anti-melanoma antibody (99Tcm-AMAb). Glutathione was labelled with 99Tcm by a Sn2+ reduction method with an efficiency of > 99% as determined by instant thin layer chromatography (ITLC). Anti-melanoma antibody was obtained as a kit from SORIN (Italy) and labelled with 99TcmO-4. Forty-three patients with a total of 55 biopsy-proven metastatic melanoma foci, 1 ocular melanoma and 20 benign pathologic foci, also confirmed by ultrasound, computed tomography and magnetic resonance imaging, were included in the study after giving their informed consent. Following the intravenous (i.v.) injection of 500 MBq 99Tcm-AMAb, scintigraphic images of the involved areas were obtained 6 h post-injection. Three days later, the same patients were given 500 MBq 99Tcm-GSH i.v. and images were obtained 6 and 24 h post-injection. The images were classified as positive (focal abnormal accumulation) or negative. Quantitative evaluation was also applied. Regions of interest were drawn over the involved areas and nearby soft tissues and the target-to-nontarget (T/NT) ratios obtained with 99Tcm-AMAb (T/NT: 1.92 +/- 0.2) and 99Tcm-GSH (T/NT: 1.84 +/- 0.2) were compared (0.1 < P < or = 0.3). The sensitivity (and specificity) of 99Tcm-AMAb and 99Tcm-GSH in the detection of malignant melanoma metastases were 91% (95%) and 84% (90%), respectively. Compared with 99Tcm-AMAb, the advantages of 99Tcm-GSH are lower levels of blood radioactivity, lower costs and easy in-house preparation. In conclusion, our results show that 99Tcm-GSH is a potentially useful radiopharmaceutical for the detection of metastases of malignant melanoma.

The release of isoconazole nitrate from different suppository bases: in-vivo release of drug labelled with 99mTc in rabbits.

The influence of the suppository bases on the in-vivo release of 99mTc-labelled isoconazole nitrate was investigated. The single-dose vaginal suppository formulations for local treatment of vaginitis were prepared by a fusion method using polyethylene glycols, Witepsol H15, Novata BD and Cremao. Prepared vaginal suppositories containing solid-labelled substance were applied to the vagina of rabbits and at 0, 2 and 24 h after administration, the amounts of radioactivity in the vagina were detected by the SPECT Gamma Camera and the release rates of the drug were calculated. The percent released was found to be in the following order; polyethylene glycol (PEG) 6000 > PEG 4000 > Witepsol > PEG 1500 > Novata BD > Cremao. The results obtained in both in-vitro and in-vivo studies indicated that the vaginal suppository of isoconazole nitrate prepared with polyethylene glycols could confidently be used in therapy.

Moyamoya disease in twins.

Tc-99m HMPAO SPECT was used to evaluate regional blood flow in one monozygotic twin who had angiographically proven moyamoya disease. Focal and global reduced regional cerebral perfusion were observed in both patients with Tc-99m HMPAO SPECT studies. There was good correlation between the localization and degree of regional cerebral blood flow abnormalities and the severity and stage of clinical symptoms on angiography. These results suggest that Tc-99m HMPAO SPECT is a useful method in the detection of hemodynamic abnormalities in moyamoya disease.

Evaluation of palpable breast masses with 99Tcm-MIBI: a comparative study with mammography and ultrasonography.

We evaluated the feasibility of 99Tcm-methoxyisobutylisonitrile (MIBI) as a tumour localizing agent in patients with palpable breast masses in comparison with mammography and ultrasonography (US). Forty-one patients with palpable masses were studied. An additional 12 women with no palpable breast anomaly also underwent 99Tcm-MIBI breast study. Multiple views were obtained and semiquantitative evaluation was applied. Mammography and US revealed all of the malignant breast masses but differential diagnosis of fibroadenomas could not be achieved. Twenty-five of 27 breast carcinomas were detected using 99Tcm-MIBI scintigraphy. Two patients with invasive lobular carcinoma showed absent MIBI accumulation. Eight of 14 axillary lymph-node metastases showed positive uptake (57%). Twelve of 14 patients with pathologically proven benign breast lesions did not demonstrate any MIBI accumulation. Focal MIBI uptake could be observed in two fibroadenomas. The sensitivity and the specificity of semiquantitative MIBI analysis were 93 and 86%, respectively. Subjective grading offered no additional help in the further differentiation of malignant breast masses. There was no significant difference between histopathological types of breast carcinomas and uptake grades. Our results indicate that 99Tcm-MIBI scintigraphy may provide additional information in the differentiation of malignant pathologies from benign lesions in patients with palpable breast anomalies.

The value and limitations of 201Tl scintigraphy in the evaluation of lung lesions and post-therapy follow-up of primary lung carcinoma.

In this study 201Tl planar scintigraphy and single photon emission computed tomography (SPECT) were performed in 92 patients with solitary lung lesions in order to distinguish malignant versus benign and metastatic masses and to evaluate the radiotherapy response of 15 primary lung carcinomas. Semiquantitative and quantitative analyses were carried out and the results were compared with histopathological diagnosis. The overall sensitivity, specificity and accuracy of semiquantitative analysis were 56, 71 and 58%, and quantitative evaluations were 88.8, 100 and 92%, respectively. Retention indexes (RI) derived from the early and delayed images were 2.9 +/- 1.3 for primary lung carcinomas, -2.78 +/- 0.9 for benign conditions and -2.3 +/- 1.5 for metastatic pulmonary lesions. 201Tl scintigraphy seems to be a sensitive modality for differentiating malignancies from benign conditions since the difference between those two pathologies is significant. However, this procedure has a limited value in distinguishing metastatic pulmonary lesions from benign pathologies, and in tissue characterization of primary lung carcinomas. On the other hand, a good correlation was observed between 201Tl lung scintigraphy and clinical diagnostic examination during postradiotherapy follow-up of inoperable pulmonary neoplasia.

Visualization of bone pathologies and lung cancer with 99mTc-glucose phosphate: a comparative study.

Glucose phosphate (GP) labelled with 99mTc was used to obtain scintigraphic images of bone lesions in one group of patients (n = 28) and of lung tumors in another (n = 35). All bone lesions detected by 99mTc-MDP were also demonstrated by 99mTc-GP; all lung tumors except 4 were detected by 99mTc-GP, the failure rate being about the same as that for 67Ga. The use of 99mTc-GP is preferable to that of 99mTc-MDP because the former does not accumulate in normal bone; the advantage of 99mTc-GP over 67Ga lies in its better physical characteristics and in the fact that the result of the study is available within a few hours rather than three days.