Detection of 99mTc-sestamibi uptake in brown adipose tissue with SPECT-CT.
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Biomedical subjects
Publications and source records attributed to Tarik Belhocine.
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Cutaneous melanoma is one of the most deadly malignancies. Although it accounts for approximately 4% of all cancer cases, it ac-counts for approximately 79% of skin cancer-related deaths. In the past few years, the nuclear medicine platform used in the management of melanoma has extended to biochemical and structural imaging. In clinical practice, integrated positron emission tomography/CT devices allow anatomic and metabolic characterization of meta-static disease in a single study. Similarly, more accurate localization of sentinel nodes in a 3-D space now is feasible with hybrid single photon emission CT/CT system. In translational research, [18F]fluorodeoxyglucose probes have been designed to optimize the detection of melanoma tumor sites in vivo.
The clinical added-value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG PET) in the management of oncology patients is increasingly documented. In the present review, we discuss both the benefits and the limitations of 18FDG PET in different cancers. Considering the literature data and our own experience, we also indicate the best clinical approach to optimize the use of metabolic imaging in oncology.
Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer with neuroendocrine differentiation. We studied the potential value of 18FDG PET in the management of MCC. Eleven patients with MCC were examined by 18FDG PET and PET-CT for staging purpose (n=4) or for detection of recurrence (n=7). Qualitative and quantitative interpretation of PET studies was performed routinely. 18FDG PET observations were compared to clinical and radiological findings. In 6 patients, PET findings were also compared to histology. In 7 patients, the 18FDG tumor uptake was compared to the MCC proliferative activity expressed by the Ki-67 index. 18FDG PET was contributive in 10/11 MCC patients. In 7 patients, 18FDG PET detected focal lesions or a disseminated stage of the disease including dermal, nodal and visceral metastases. In 3 patients, a normal 18FDG PET confirmed complete remission of disease. Most MCC patients exhibited highly 18FDG-avid sites suggestive of increased glucose metabolism. This imaging pattern was related to a high proliferative activity (Ki-67 index >50%). In 1 patient with a weakly proliferative nodal MCC (Ki-67<10%), a false negative result was yielded by metabolic imaging. In 4/11 patients, 18FDG PET revealed an unsuspected second neoplasm in addition to MCC. It is concluded that whole-body 18FDG PET may be useful in the management of MCC patients. However, a normal 18FDG PET aspect cannot rule out MCC with low proliferative activity.
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In recent years, the imaging of drug-induced apoptosis has become one of the centers of interest in experimental and clinical research. In particular, the accurate monitoring of chemosensitivity as well as the early prediction of chemoresistance in response to various pro-apoptotic interventions are critical requirements for the best management of oncology patients. The use of technetium [(99m)Tc]-labeled annexin V on animal and human models of cancers provides a proof of principle for the feasibility of a non-invasive, in vivo detection of an apoptotic signal and then for the early assessment of tumor response in the course of chemotherapy. Although promising, however, the initial clinical data point out on the technical limitations that are still to be resolved in terms of tumor-to-background ratio and optimal timing for the imaging of apoptosis. In the present review article, we report the results of animal studies aimed to the evaluation of apoptotic peaks following chemotherapy. In the light of these basic research works, we analyze the profiles of radiolabeled annexin V uptake over time as observed in clinical trials. We then discuss possible new imaging strategies designed to optimize the visualization of apoptotic changes within tumor tissues using the [(99m)Tc]-labeled annexin V. We also suggest longer lived forms of radiolabeled annexin V designed to better understand the temporal patterns of apoptotic tumor response, which in turn, may help to capture the best time-window for the imaging of cell death.
STUDY OBJECTIVES: To study the ability of positron emission tomography (PET) using 18-fluorodeoxyglucose (FDG) to distinguish between benign and malignant disease in exudative pleural effusions and pleural thickening. DESIGN: Prospective study of 98 consecutive patients presenting with either pleural thickening or an exudative pleural effusion. SETTING: Department of pulmonary medicine of a university hospital. METHODS: FDG-PET was performed on each subject before invasive procedures were used to determine the etiologic diagnosis. FDG-PET data were analyzed by visual interpretation. RESULTS: Sixty-three of 98 patients were found to have malignant pleural disease after histologic analysis. Sixty-one of 63 patients with histologically confirmed malignant disease showed FDG uptake within the area of pleural thickening. Uptake was graded as intense in 51 cases and moderate in 10 cases. Only two patients with malignant pleural disease did not show increased FDG uptake. FDG-PET imaging showed an absence of FDG uptake, and correctly classified 31 of 35 benign lesions. For the remaining four lesions, intense FDG uptake was seen in one case of parapneumonic effusion, while moderate and localized uptake was observed in one parapneumonic, one tuberculous, and one uremic pleurisy. The sensitivity of the method to identify malignancy was 96.8% with a negative predictive value of 93.9%, while its specificity was 88.5% and its positive predictive value was 93.8%. CONCLUSIONS: Our results suggest that FDG-PET is an effective tool for differentiating between benign and malignant pleural diseases.
Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)FDG PET) plays a major role in the management of oncology patients. Owing to the singular properties of the glucose tracer, many patients suffering from non-malignant diseases such as inflammatory or infectious diseases may also derive clinical benefit from the appropriate use of metabolic imaging. Large vessel vasculitides such as giant cell arteritis and Takayasu arteritis are other examples that may potentially extend the field of (18)FDG PET indications. The purpose of the present article is to assess the feasibility of metabolic imaging in vasculitis on the basis of the current literature data. In particular, the clinical context and the (18)FDG imaging patterns seen in patients with large vessel vasculitis are analysed in order to identify potential indications for metabolic imaging.
In nuclear medicine, [18F]-fluorodeoxyglucose positron emission tomography (18FDG PET) and lymphatic mapping and sentinel lymphadenectomy (LM/SL) may significantly improve the staging of primary cervical cancers. Indeed, the disease progresses in a 'level by level' fashion to regional nodes through the lymphatic channels, and also to extra-nodal sites via the hematogenous stream. Additionally, the sub-optimal efficacy of routine radiological protocols, while new combined therapies are proving to be more efficient, stresses the need for alternative staging procedures. Current data suggest that LM/SL accurately reflects the regional lymph node status in early stage cervical cancers, and thus could avoid unnecessary complete lymphadenectomies. Also, whole body 18FDG PET may provide valuable insights on extra-pelvic and distant tumor spreading, with a significant impact on treatment choices. If these promising results are confirmed on large controlled trials, LM/SL and 18FDG PET imaging could be incorporated in the routine staging work-up of primary cervical cancers.
RATIONALE: Induction of apoptosis in sensitive tumor cells is the main mechanism of action of chemotherapy agents in human cancers. Also, the assessment of drug-induced apoptosis soon after chemotherapy may be an early predictor of treatment efficacy. PATIENTS AND METHODS: A phase I/II study was prospectively conducted in 15 patients presenting with proven lung cancers (n = 10), breast cancers (n = 2), and lymphomas (n = 3) to assess the value of the (99m)Tc-radiolabeled recombinant human (rh) Annexin V for imaging apoptosis immediately after completion of the first course of chemotherapy. Early Annexin V findings post-chemotherapy (day+1, day+2) were also compared to the tumor status at 6 to 12 weeks post-treatment. RESULTS: All lung and lymphoma patients with an increased tracer uptake post-treatment (n = 8) had either partial or complete tumor response. Five patients with no tracer uptake had progressive disease. However, two breast cancers had a response to treatment, although no significant tracer uptake was observed. Tumor response and survival time were significantly correlated with the (99m)Tc-labeled Annexin V uptake. No serious events related to tracer administration were noted. CONCLUSION: : Preliminary results of this pilot study demonstrate the feasibility of the 99mTc-labeled Annexin V uptake for the in vivo imaging of apoptosis after one course of chemotherapy. If confirmed on larger series, these promising results may open new perspectives in the management of oncology patients.
The aim of this study was to assess the usefulness of fluorine-18 fluoro-2-deoxy- D-glucose positron emission tomography (FDG PET) in the post-therapy surveillance of endometrial carcinomas. Forty-one fully corrected whole-body PET studies were performed in 34 women with previously treated endometrial cancers as a part of their follow-up programme. In 28 studies, FDG PET was indicated to localise a recurrence suspected at the control visits on the basis of clinical examination and/or radiological abnormalities (chest X-ray, CT or MRI) and/or elevated tumour marker levels (CA125, CEA). Another 13 studies were performed as a simple surveillance procedure. Overall, in 26 studies PET detected recurrent disease, which was confirmed either by histology ( n=7) or by clinical and radiological outcomes ( n=19). In 88% of the cases, the PET findings confirmed recurrence suggested by routine follow-up. In the remaining 12% of cases, PET detected asymptomatic recurrences that were unsuspected at the control visits. Whole-body PET accurately localised the site of confirmed recurrences as being above and below the diaphragm in 50%, only below the diaphragm in 35% and only above the diaphragm in 15%. In one patient, however, PET missed microscopic lung metastases shown on thoracic CT, and in three studies, metabolic imaging results were not confirmed. In 11 of 12 negative PET studies, no subsequent clinical or radiological recurrences were observed with a median follow-up of 10 months. Overall, the results of PET agreed well with the final diagnosis (Cohen's kappa coefficient =0.78). In 9/26 patients (35%) with confirmed recurrences, the PET findings significantly altered the treatment choice by detecting either clinically or radiologically unsuspected distant metastases. The sensitivity, specificity, diagnostic accuracy and positive and negative predictive values of FDG PET imaging in the post-therapy surveillance of endometrial carcinomas were 96%, 78%, 90%, 89% and 91%, respectively. Indeed, the high likelihood ratio for a positive test result (4.5) and the low likelihood ratio for a negative test result (0.05) demonstrated the clinical utility of metabolic imaging in "ruling in" disease as well as "ruling out" recurrence. In conclusion, whole-body FDG PET appears useful in the post-therapy surveillance of endometrial cancers, both for the accurate localisation of suspected recurrences and for the detection of asymptomatic recurrent disease.
OBJECTIVE: The objective of this study was to assess the contribution of [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG PET) imaging in the management of cervical cancer. METHODS: Fully corrected whole-body PET was performed in 60 patients (pts) with proven cervical cancer. In pretreatment staging, 22 pts underwent PET in addition to routine protocol including International Federation of Obstetrics and Gynecology (FIGO) staging and pelvic magnetic resonance imaging (MRI). Eighteen of them had pelvic lymphadenectomy. After treatment, PET was performed in 38 pts routinely followed up by clinical and radiological examinations. Results of PET and routine protocols were compared to final diagnoses, including histological findings in 31 pts and clinical outcomes in the other cases. Median follow-up time was 12 +/- 7.3 months. RESULTS: In all but 2 patients (FIGO stage IA), both PET and MRI detected the primary tumor. In 6 pts, MRI alone noted loco-regional tumor spread but PET localized 9 unsuspected extrapelvic nodal sites (6 para-aortic, 2 mediastinal, and 1 supra-clavicular). However, PET missed 8 microscopic pelvic nodal metastases. In 18% of the patients, PET staging significantly influenced the treatment choices. In follow-up, PET accurately diagnosed a recurrent disease in 13 pts with falsely negative or equivocal conventional imaging (CI). Ten patients with a negative PET were still in complete remission after a minimal follow-up time of 12 months. Overall, the agreement of PET with final diagnosis was significantly better than that of routine protocol (P < 0.05). CONCLUSIONS: Whole-body (18)FDG PET appears useful in the management of cervical cancer, in particular for staging extrapelvic metastases or optimally detecting a recurrence. MRI is better indicated for evaluating the loco-regional status of the disease.
PRIMARY PURPOSE: The staging of regional nodes by means of sentinel node detection has been shown to accurately detect subclinical nodal metastases from cutaneous melanoma. On the other hand, the oncological applications of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG PET) are, nowadays, firmly established. However, the sensitivity of such metabolic imaging for staging the regional nodes in primary melanoma remains debatable. We prospectively assessed the actual value of PET for detecting sentinel node metastases in 21 consecutive patients presenting with early-stage melanoma. MATERIALS AND METHODS: Twenty-one melanoma patients scheduled for lymphatic mapping and sentinel lymphadenectomy underwent fully corrected whole-body PET using 18FDG. In all cases, the disease was initially classified as either stage I or II, from the latest version of the American Joint Committee on Cancer staging system. The sentinel node detection was systematically performed within the week following the PET scan. Serial sections of the sentinel nodes were analyzed by both conventional pathology and immunohistochemical staining. Metastatic sentinel nodes were also assessed for the size of tumor deposits and the degree of nodal involvement (focal, partial, or massive). The median follow-up time was 12 months. RESULTS: Six of the 21 patients (28.5%) had an involved sentinel node. PET was positive in only one case with a sentinel node >1 cm. In the five other cases, the sentinel nodes missed by PET were <1 cm with focal and/or partial involvements. One patient, free of regional nodal metastases in both sentinel node detection and PET imaging, had, however, a same-basin recurrence 3 months later. In another case, PET had one false positive result. Overall, the sentinel detection of subclinical nodal metastases had a sensitivity of 86%. PET detected only 14% of sentinel node metastases. CONCLUSIONS: Sentinel node detection remains the procedure of choice for detecting subclinical lymph node involvement from primary cutaneous melanoma. Owing to its limited spatial resolution, PET appears insufficiently sensitive to identify microscopic nodal metastases. As a practical consequence, metabolic imaging is not recommended as a first-line imaging strategy for staging regional lymph nodes in patients with stage I or II melanoma.
PURPOSE: Many anticancer therapies exert their therapeutic effect by inducing apoptosis in target tumors. We evaluated in a Phase I study the safety and the feasibility of (99m)Tc-Annexin V for imaging chemotherapy-induced apoptosis in human cancers immediately after the first course of chemotherapy. EXPERIMENTAL DESIGN: Fifteen patients presenting with lung cancer (n = 10), lymphoma (n = 3), or breast cancer (n = 2) underwent (99m)Tc-Annexin V scintigraphy before and within 3 days after their first course of chemotherapy. Tumor response was evaluated by computed tomography and (18)F-fluoro-2-deoxy-D-glucose positron emission tomography scans, 3 months in average after completing the treatment. Median follow-up was 117 days. RESULTS: In all cases, no tracer uptake was observed before treatment. However, 24-48 h after the first course of chemotherapy, 7 patients who showed (99m)Tc-Annexin V uptake at tumor sites, suggesting apoptosis, had a complete (n = 4) or a partial response (n = 3). Conversely, 6 of the 8 patients who showed no significant posttreatment tumor uptake had a progressive disease. Despite the lack of tracer uptake after treatment, the 2 patients with breast cancer had a partial response. Overall survival and progression-free survival were significantly related to tracer uptake in treated lung cancers and lymphomas (P < 0.05). No serious adverse events were observed. CONCLUSIONS: Our preliminary results demonstrated the feasibility and the safety of (99m)Tc-Annexin V for imaging apoptosis in human tumors after the first course of chemotherapy. Initial data suggest that early (99m)Tc-Annexin V tumor uptake may be a predictor of response to treatment in-patients with late stage lung cancer and lymphoma.