Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee.

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.

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.

Assessment of chemotherapy-induced changes in bone sarcomas: clinical experience with 99Tcm-MDP three-phase dynamic bone scintigraphy.

The aim of this study was to evaluate the value of three-phase dynamic bone scintigraphy (TPBS) in the assessment of the response of bone sarcomas to pre-operative chemotherapy and to correlate serial scintigraphic changes with histological findings. The study group comprised 27 patients (osteogenic sarcoma, n = 20; Ewing's sarcoma, n = 5; malignant fibrous histiocytoma, n = 2) with a mean age of 19.2 years. All patients received 99Tcm-methylene diphosphonate TPBS before and after pre-operative chemotherapy. Each phase of the imaging procedure was interpreted qualitatively and quantitatively. The percentage of tumour necrosis was analysed on resection materials following surgery. Histologically, 12 patients were non-responsive (tumour necrosis less than 90%) and 15 patients were responsive (tumour necrosis more than 90%). A decrease in the tumour blood flow ratio and extension were the most notable findings in the responders. The mean change in the tumour blood flow ratio following therapy was 58.7 +/- 8.3% and 19.9 +/- 26.6% (P < 0.005) in responders and non-responders respectively. The accuracy of three-phase imaging and static bone scintigraphy was 88% and 74% respectively. Since bone scintigraphy is a valuable technique owing to its ability to detect distant metastases in clinically early disease, TPBS should be helpful in monitoring therapy effects without any additional cost or radiation dose.

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.

Correlation of 99mTc-sestamibi uptake with blood-pool and osseous phase 99mTc-MDP uptake in malignant bone and soft-tissue tumours.

Technetium-99m-sestamibi (99mTc-MIBI) imaging is a well-established modality in oncologic investigations. The current study aimed to investigate whether any relationship could be found between 99mTc-MIBI uptake and local perfusion in malignant bone and soft-tissue tumours. It also aimed to compare 99mTc-MIBI images with those of technetium-99m-methylene diphosphonate (99mTc-MDP) bone scintigraphy with regard to the activity distribution pattern, intensity and lesion extension. The study group included 24 patients with various bone and soft-tissue tumours. Three-phase bone scintigraphy and 99mTc-MIBI studies were performed within the same week before any surgical and therapeutic intervention. Images were evaluated visually and quantitatively using regions of interest (ROIs) over the lesion and adjacent normal tissue. The 99mTc-MIBI study was positive with varying degrees of uptake (range, 1.4-5.3). The mean 99mTc-MIBI uptake and 99mTc-MDP blood-pool and osseous phase activity ratios were 2.5 +/- 0.5, 2.8 +/- 1.0 and 5.5 +/- 4.0, respectively. The correlation between the 99mTc-MIBI uptake and blood-pool ratios was 0.70 (P<0.05). While activity distribution patterns were in agreement in 99mTc-MIBI and blood-pool images in the majority of cases, 99mTc-MIBI better delineated tumour viability and extension in five cases. In conclusion, 99mTc-MIBI accumulation shows a reasonable correlation with blood-pool uptake assuming the presence of multifactorial mechanisms in addition to local hyperaemia. Better delineation of tumour outlines and cellular activity seems to be an advantage of 99mTc-MIBI scintigraphy which may be helpful in the evaluation of musculoskeletal tumours.

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.

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.

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.

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.

False-negative scintigraphy with Tc-99m sestamibi in stage IV neuroblastoma.

Tc-99m sestamibi, originally developed for myocardial studies, has been used as a tumor-seeking agent. Recently, the agent also was reported to be a functional tracer to predict multidrug resistance-related p-glycoprotein expression in tumor tissue. The current report presents the authors' experience with sestamibi tumor scintigraphy in a neuroblastoma. Although I-131 MIBG tumor imaging and Tc-99m MDP bone scanning accurately demonstrated the extent of the disease, Tc-99m sestamibi showed no accumulation in primary and metastatic foci. Lack of sestamibi uptake was initially thought to be suggestive of failure to respond to chemotherapy because of p-glycoprotein expression. However, the patient responded well to chemotherapy and complete remission was achieved. The failure of Tc-99m sestamibi to detect a neuroblastoma and the lack of sestamibi accumulation in the tumor may not always be related to chemotherapy resistance.

Thallium-201 uptake in myositis ossificans. Potential pitfall in diagnosis.

Myositis ossificans is primarily a disorder of adolescents or adults, whereby an area of muscle mass undergoes progressive ossification. Its radiographic and scintigraphic appearances have been well documented. In this paper, a case of histopathologically demonstrated myositis ossificans in the proximal thigh with unexpected TI-201 accumulation was presented.

The role of 99mTc-MIBI scintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response.

The occurrence of multidrug resistance (MDR), which is in part due to the overexpression of P-glycoprotein (Pgp), is a major problem in neoadjuvant therapy of malignant musculoskeletal tumours. The aim of this study was to investigate the role of technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy for functional imaging of the MDR1 phenotype in patients with musculoskeletal sarcomas. We aimed to compare 99mTc-MIBI uptake and washout kinetics with the expression of Pgp and with chemotherapy response. Twenty-five patients (16 males and 9 females, aged between 8 and 65 years) with malignant musculoskeletal tumours were studied. After injection of 555-740 MBq 99mTc-MIBI, dynamic flow images of the involved area were obtained for 3 min, and planar images were acquired at 10 min and 1 h. From the dynamic images, a tumour perfusion index (TPI) was obtained using Patlak-Rutland analysis. Tumour to background (T/B) ratios of both early and delayed images and percent wash-out rate (WR%) of 99mTc-MIBI were calculated. Immunohistochemical analysis of Pgp was performed on biopsy specimens and the degree of expression was graded according to a semiquantitative scoring system, from 0 to 6. After neoadjuvant therapy, tumour response was assessed by examining the ratio of viable cells and by detecting percent necrosis. Scintigraphic results were compared with Pgp status and therapy response. Irrespective of the Pgp status, all patients showed significant perfusion and 99mTc-MIBI uptake in early images. There was not a significant correlation between T/B ratios of early and delayed images and Pgp expression. We observed a positive correlation between WR% and Pgp status (r=0.61, P<0.01), and the wash-out rate of 99mTc-MIBI was significantly higher in patients with high Pgp expression than in those with a low Pgp score (33% +/- 9% vs 17% +/- 9%). Therapy response was determined in 21 of 25 patients, and in only 5 of 21 cases was the percent necrosis more than 90%. Neither Pgp expression rate nor WR% was found to show a significant correlation with percent necrosis in the bulk tumour specimens. In conclusion, the initial uptake of 99mTc-MIBI in bone and soft tissue sarcomas did not correlate with Pgp expression. A relationship was found between the wash-out rate of 99mTc-MIBI and the Pgp score, with a significant difference in WR% being observed between patients with high and patients with low Pgp expression.