Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating 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 article was 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. These guidelines were prepared 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 Committee.

UNLABELLED:In vitro studies have demonstrated that (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) is a transport substrate of multidrug resistance (MDR)-related proteins. The aim of this clinical study was to evaluate whether (99m)Tc-MIBI scintigraphy was a functional imaging tool for in vivo detection of multidrug resistance-associated protein (MRP) expression in osteosarcoma and to investigate the role of MRP and (99m)Tc-MIBI imaging to predict the clinical outcome. We also examined whether the scintigraphic parameters would help to distinguish the functional capacity of P-glycoprotein (Pgp) and MRP.METHODS:Twenty-four patients with a diagnosis of osteosarcoma were studied before neoadjuvant chemotherapy. Tumor-to-background ratios of both early (10 min) and delayed (1 h) images and the percentage washout rate (WR%) of (99m)Tc-MIBI were calculated. Immunohistochemical analysis of MRP and Pgp was performed on biopsy specimens, and the response to preoperative chemotherapy was assessed by histopathologic examination.RESULTS:Fifteen of 24 osteosarcoma samples in our series (62.5%) showed significant expression of MRP. The level of MRP expression was significantly correlated with the WR% of (99m)Tc-MIBI (r = 0.58, P = 0.003), and the WR% of (99m)Tc-MIBI was significantly faster in patients with high MRP expression than in those with a low MRP score (P = 0.007). The clearance rate of (99m)Tc-MIBI was significantly slower in tumor samples with negative or low expression of both Pgp and MRP (16% +/- 6.2%) when compared with osteosarcomas with high expression of both proteins (31.7% +/- 8.7%) (P = 0.001). There was not a significant difference between the WR% of (99m)Tc-MIBI in tumors with coexpression of both proteins and in tumors with high expression of either Pgp or MRP. Both the rate of MRP expression and the WR% of (99m)Tc-MIBI were significantly correlated with response rate.CONCLUSION:Our results suggest that the WR% of (99m)Tc-MIBI is correlated with MRP expression. Both the WR% of (99m)Tc-MIBI and MRP expression are correlated with therapy response. (99m)Tc-MIBI can be used as a general probe for functional imaging of both Pgp and MRP; however, it is not capable of differentiating the functional status of either MDR-related glycoprotein.

Twenty-five patients were treated for osteosarcoma of the extremity at Ege University Hospital. Eight of them were metastatic. All patients received cisplatin, doxorubicin, ifosfamide, and methotrexate preoperatively. Twenty-three patients underwent surgery at around week 15 (11-18 weeks). All but one underwent limb-sparing surgery. While good responders continued to receive the same drugs, poor responders were given the same regimen before 1996, but high-dose ifosfamide alone after 1996. For all patients the projected event-free survival (EFS) rates were 63.5% at 2 years and 53% at 5 years. The projected overall survival (OS) rates were 72% at 2 years and 62% at 5 years. For nonmetastatic patients, 5-year EFS and OS rates were 67% as compared with metastatic patients (25 and 50%)( p = .01 for EFS; p > .05 for OS). The results show that nonmetastatic patients with osteosarcoma of the extremity have favorable prognosis on this therapy regimen, allowing a high rate of limb-sparing surgery.

Technetium-99m-sestamibi (Tc-99m-MIBI) imaging is a well-established modality in oncologic investigations. The current study aimed to investigate whether any relationship could be found between Tc-99m-MIBI uptake and local perfusion in malignant bone and soft-tissue tumours. It also aimed to compare Tc-99m-MIBI images with those of technetium-99m-methylene diphosphonate (Tc-99m-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 Tc-99m-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 Tc-99m-MIBI study was positive with varying degrees of uptake (range, 1.4-5.3). The mean Tc-99m-MIBI uptake and Tc-99m-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 Tc-99m-MIBI uptake and blood-pool ratios was 0.70 (P<0.05). While activity distribution patterns were in agreement in Tc-99m-MIBI and blood-pool images in the majority of cases, Tc-99m-MIBI better delineated tumour viability and extension in five cases. In conclusion, Tc-99m-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 Tc-99m-MIBI scintigraphy which may be helpful in the evaluation of musculoskeletal tumours. ((C) 2001 Lippincott Williams & Wilkins).

In this study, we investigated prospectively the diagnostic role of Tc-99(m)-MIBI for staging and for predicting the therapeutic response of stage nr neuroblastoma compared wth I-131-MIBG imaging and Tc-99(m)- MDP bone scintigraphy. Nine patients (4 girls and 5 boys aged 1-7 years) with suspected or proven stage IV neuroblastoma were studied with Tc-99(m)-MIBI at initial diagnosis and after 12-18 months of multidrug therapy. After the injection of 80 MBq.kg(-1) Tc-99(m)-MIBI, early (10 min) and delayed (1 h) images were obtained. The data were correlated with I-131-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 I-131-MIBG scintigraphy. None of the primary lesions demonstrated significant Tc-99(m)-MIBI accumulation. Sestamibi was positive in 16 of 41 MIBG-avid metastatic lesions. After six courses of multidrug chemotherapy, 30 I-131-MIBG-avid neuroblastoma metastases that were Tc-99(m)-MIBI-negative at the time of diagnosis still did not show significant sestamibi accumulation. Follow-up demonstrated that all lesions that were Tc-99(m)-MIBI-avid at the time of diagnosis remained negative. Of these 16 lesions, seven were positive for I-131-MIBG accumulation with no reduction in size, and nine showed resolution after therapy. New metastatic foci detected by MIBG scintigraphy did not accumulate Tc-99(m)-MIBI. Clinical evaluation of patients with no Tc-99(m)-MIBI uptake in primary and secondary sites of neuroblastoma confirmed that they were resistant to multidrug chemotherapy. AII Tc-99(m)-MIBI-positive lesions, irrespective of clinical outcome, demonstrated significant clearance of tracer on the delayed images. We conclude that Tc-99(m)-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. ((C) 1999 Lippincott Williams & Wilkins).

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.

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.

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 (99T)c(m)-methylene diphosphonate TPBS before and after pre-operative chem otherapy. 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 moan 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. ((C) 1999 Lippincott Williams & Wilkins).

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 201T1 cardiac imaging. Sixteen patients (14 males, 2 females) were studied by same-day exercise-rest 99Tcm-tetrofosmin imaging and exercise, rest and reinjection 201T1 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 201T1 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 ≤ 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 201T1 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 201T1 = 1.92 ± 0.8; P ≤ 0.001) and in Group 2 (mean grade of 99Tcm-tetrofosmin = 0.79 ± 0.65 and of 201T1 = 0.95 ± 0.65; P ≤ 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 201T1 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.