Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

Uterine leiomyosarcoma metastatic to thyroid shown by 18F-FDG PET/CT imaging.

About one third of focal thyroid uptakes in a fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) study are malignant, the most frequent histological type being papillary carcinoma. Metastases to the thyroid account for approximately 7.5% of thyroid malignancies and come mainly from kidney, lung, head and neck, and breast cancers. We report the case of a 64-year-old woman presenting a fast growing thyroid nodule whose primitive or metastatic origin was not obvious, for which 18F-FDG PET/CT helped in the diagnostic process and in the later management of the patient. Histopathologic findings finally revealed a metastasis of uterine leiomyosarcoma.

Relationship between lymphoscintigraphy and clinical findings in lower limb lymphedema (LO): toward a comprehensive staging.

Although radionuclide lymphoscintigraphy (RNL) is widely used diagnostically for patients with lymphedema (LE), it has not been utilized for LE staging, which is still based upon clinical findings. The aim of this work is to establish whether the results of both conventional RNL and fusion imaging obtained from hybrid detectors may be used for a comprehensive clinicoimaging staging in LE. Radiolabeled nanocolloids (0.2 ml) were subcutaneously injected in 4,328 patients (23-78 years) with clinical lower limb LE and without venous disease. Patients were classified according to the ISL classification and had a minimal follow-up of 2 years. Images were taken 60 minutes after the injection as a whole body scanning and fusion images of functional SPET and anatomical CT. Clinical and RNL results were not in accordance, and a specific RNL staging was established. The association of clinical and functional staging yields a new method to grade LE patients, and this staging correlated with treatment efficacy. RNL is an important tool in lymphology, and its association with the clinical evaluation offers a new grading system which may be able to delineate patients with good prognosis, patients at risk for a complex decongestive physiotherapy (CDP) failure, and patients who may benefit from other therapeutic protocols.

Association of peripheral multifocal choroiditis with sarcoidosis: a study of thirty-seven patients.

OBJECTIVE: To assess the clinical spectrum of peripheral multifocal choroiditis (PMC) and its association with sarcoidosis. METHODS: Thirty-seven patients examined between November 1997 and November 2001 who met all diagnostic criteria for PMC were included in this retrospective study. Patients were assessed for the following signs of sarcoidosis: typical changes on chest radiography or computed tomography; predominantly CD4 lymphocytosis in bronchoalveolar lavage fluid; elevated serum angiotensin-converting enzyme levels; elevated gallium uptake; and noncaseating granuloma on biopsy. RESULTS: Most of the patients were female (30 of 37; 81%) and white (30 of 37; 81%). Mean +/- SD age at onset was 57.5 +/- 18.7 years. Seven (19%) of the 37 patients had biopsy-proven sarcoidosis and 18 patients (49%) with presumed sarcoidosis met at least 2 of the above-mentioned criteria for sarcoidosis but had normal biopsy results. Twelve patients (32%) had an indeterminate diagnosis. Patients with presumed sarcoidosis did not differ from those with proven sarcoidosis as regards the above-mentioned criteria, except for noncaseating granuloma, implying that more than two-thirds of patients (predominantly whites) had underlying sarcoidosis. Most patients with positive gallium scintigraphy had increased mediastinal uptake, as described in sarcoidosis. Patients with underlying sarcoidosis had more severe visual impairment due to cystoid macular edema (CME). Weekly methotrexate (0.3 mg/kg) seemed to control CME. CONCLUSION: White patients with PMC should be considered to have sarcoidosis. The identification of sarcoidosis in patients with severe ocular disease can help with therapeutic choices.

Somatostatin receptors 2 and 5 are the major somatostatin receptors in insulinomas: an in vivo and in vitro study.

Somatostatin (SRIF) receptors (sst) are present on normal pancreatic endocrine beta-cells. However, the use of SRIF analogs in the scintigraphic imaging of insulinomas and in the medical management of these tumors seems to be restricted to a subgroup of patients. The aim of this study was to determine the prevalence of sst expression in vitro and characterize sst subtype binding in insulinomas and its correlation with in vivo sst receptor scintigraphy (SRS). In vitro studies were performed on 27 insulinomas from 25 patients: 22 with benign and three with malignant tumors. Semiquantitative RT-PCR of sst mRNAs was performed for 20 of these insulinomas. Sst2 and sst5 were expressed in 70%, sst1 in 50%, and sst3 and sst4 subtypes only in 15-20% of the tumors. (125)I-Tyr(0)DTrp(8)SRIF(14) binding was assessed by quantitative autoradiography in 18 insulinomas, and competition experiments were performed with SRIF(14) and L797-591, L779-976, L796-778, L803-087, L817-818, selective agonists of the five sst subtypes, and BIM23244, a selective agonist of sst2 and sst5. Significant specific binding was observed in 72% of the insulinomas. Displacement experiments with ligands of higher affinity for each of the sst receptors revealed significant binding with the sst2 and sst5 ligands in 72%, sst3 in 44%, sst1 in 44%, and sst4 in 28% of cases. All insulinomas displaying sst2 binding were also sst5 sensitive. However, the ratio of sst5/sst2 displacement was variable and only equal to that for SRIF(14) in experiments with the sst2/sst5 agonist BIM23244. SRS was performed 10 times in nine patients; it detected 60% of the tumors, including metastases of a malignant insulinoma. All the tumors detected by SRS displayed high levels of (125)I-Tyr(0)DTrp(8)SRIF(14) binding. The mechanisms underlying the loss of expression of sst2/sst5 in a third of insulinomas remains to be determined, but this loss of expression may be involved in beta-cell dysfunction.

Whole-body positron emission tomography using fluorodeoxyglucose in patients with metastases of unknown primary tumours (CUP syndrome).

The aim of this study was to evaluate the clinical performances of whole body 2-[18F]fluorodeoxyglucose positron emission tomography (FDG PET) imaging for the detection of the primary tumour in patients with metastases of unknown origin. Forty-one patients, without previous history of known cancer (18 women and 23 men; average age 64.1 years) with metastasis confirmed by histopathological analysis were included in a retrospective study. Results of PET were compared with those of techniques used in the current conventional diagnostic procedure. All known metastatic lesions were detected by PET. There were 26 true-positive and two false-negative results. Primary tumour remained undetermined in eight patients after conventional investigations and PET. PET was superior to conventional diagnostic procedure in 11 patients and led to modify treatment in 11 patients. Sensitivity of PET was superior than computed tomography in detecting abdominal primary tumours. FDG PET is useful in patients with unknown primary tumour because its sensitivity is good and it could modify the disease management. Otherwise, PET allows the evaluation of the extent of the disease and could be used to monitor treatment efficiency. Its contribution has to be evaluated particularly in patients with primary tumour with a specific treatment.

[Positron emission tomography in clinical oncology]. / Tomographie par émission de positons en oncologie clinique.

A NEW FORM OF MEDICAL IMAGING: Positron emission tomography (PET) is used for the non-invasive in vivo visualisation of biochemical cell processes. It reveals the metabolic characteristics of neoplastic lesions and hence their identification by compensating the lack of lesion specificity of radiological techniques. VARIOUS INDICATIONS: Using the current oncology marker, 18F-fluorodeoxyglucose (FDG), excellent results with PET have been established at all stages of neoplasia, notably for the diagnosis of initial malignancy and the identification of residual lesions and early detection of relapses. Moreover, the fact that the whole of the body can be explored makes PET the tool of choice in the control of the extension and operability of cancers. With the close correlation between imaging and the metabolism of the lesions, PET is the earliest and most precise for assessing the effects of treatment. LIMITS AND PERSPECTIVES: The existence of benign inflammatory FDG binding should lead to the development of markers of other metabolisms directly linked to cell proliferation. The lack of anatomical reference points characteristic of PET does not permit the precise localisation of the lesions detected and could be corrected by combining, in a single apparatus, the PET camera and an X scan, the anatomical resolution of which is irreplaceable. This type of equipment represents the development of a new branch of medical imaging, oncological imaging.

Technetium-99m HMPAO-labeled leukocyte imaging compared with endoscopy, ultrasonography, and contrast radiology in children with inflammatory bowel disease.

BACKGROUND: The purpose of this study was to evaluate retrospectively the value of leukocyte-labeled scintigraphy, ultrasonography, and contrast radiography compared with endoscopy in children suspected of having inflammatory bowel disease (IBD). METHODS: Twenty-eight children (17 boys; mean age, 10.2 years) with IBD based on standard colonoscopic, histologic, and radiologic criteria (16 with Crohn's disease, 5 with ulcerative colitis, 5 with nonspecific colitis, I with granulomatous disease, and I with Beh,cet's disease) were included. Endoscopic, ultrasonographic, and contrast radiologic examinations were realized for 28, 23, and 19 children respectively. RESULTS: Sensitivity and specificity were 75% and 92% for leukocyte-labeled scintigraphy, 39% and 90% for ultrasonography, and 58% and 83% for contrast radiography. The authors noted discontinuous uptake for 14 of 15 true-positive results for patients with Crohn's disease and continuous uptake for 4 of 4 true-positive results for patients with ulcerative colitis. A negative correlation between scan activity index and Lloyd-Still clinical score was found for 11 patients with Crohn's disease (r = -0.77). CONCLUSIONS: Leukocyte-labeled scintigraphy, a noninvasive and reproducible technique, is a useful tool in the diagnosis and therapeutic strategy of IBD, and provides information on the presence, the intensity, and the extent of the disease, particularly in the terminal ileum. Leukocyte-labeled scintigraphy may not replace colonoscopy with biopsies for diagnosis confirmation. Its reliability seems higher than that of ultrasonography.

Detection of occult disease in breast cancer using fluorodeoxyglucose camera-based positron emission tomography.

An isolated increase of blood tumor marker CA 15.3 in breast cancer is considered a sensitive indicator for occult metastatic disease but by itself is not sufficient for initiating therapeutic intervention. We investigated the potential of camera-based positron emission tomography (PET) imaging using [18F]-fluorodeoxyglucose (FDG) to detect clinically occult recurrences in 132 female patients (age, 35-69 years) treated for breast cancer, all presenting with an isolated increase in blood tumor marker CA 15.3 without any other evidence of metastatic disease. FDG results were correlated to pathology results or to a sequentially guided conventional imaging method. One hundred nineteen patients were eligible for correlations. Positive FDG scans were obtained for 106 patients, including 89 with a single lesion and 17 with 2 or more lesion. There were 92 true-positive and 14 false-positive cases, 10 of which became true positive within 1 year. Among the 13 negative cases, 7 were false negative and 6 were true negative. Camera-based PET using FDG has successfully identified clinically occult disease with an overall sensitivity of 93.6% and a positive predictive value of 96.2%. The smallest detected size was 6 mm for a lymph node metastasis (tumor to nontumor ratio, 4:2). FDG camera-based PET localized tumors in 85.7% of cases suspected for clinically occult metastatic disease on the basis of a significant increase in blood tumor marker. A positive FDG scan associated with an elevated CA 15.3 level is most consistent with metastatic relapse of breast cancer.

Somatostatin receptor in breast cancer and axillary nodes: study with scintigraphy, histopathology and receptor autoradiography.

UNLABELLED: We conducted a prospective analysis of somatostatin receptor scintigraphy using (111)In radiolabeled pentetreotide, a somatostatin analog, in patients with breast cancer in the aim to visualize the primary tumor and axillary or parasternal metastatic extension because some malignant breast tumors express somatostatin receptors (SS-R) in 50%, approximately. An analysis of SS-R was performed by autoradiography. PATIENTS AND METHODS: Thirteen patients with clinically suspected breast tumors (T1, T2), and at least one palpable axillary node (N1) were included. In vivo planar scintigrams were acquired 1, 4, and 24 h after subcutaneous, then after intravenous injections (24 h delay between injections). Improved (111)In-pentetreotide uptake in invaded nodes after subcutaneous injection was hypothesized. Ex vivo scintigrams of surgical specimens were also acquired immediately after tumor resection and axillary dissection. Pathological examination and receptor autoradiography were performed on all surgical specimens. RESULTS: Among 11 pathologically proven malignant tumors (9 ductal and 2 lobular carcinomas), only four were scintigraphically visible although six expressed SS-R receptors in vitro. Among six pathologically proven malignant nodes, four expressed SS-R, including two visualized scintigraphically. Scintigrams acquired after subcutaneous injections were less sensitive than after intravenous injections. There were no false positive. False negatives occurred in cases with small tumors with low-density or heterogeneously distributed SS-R. There was no significant difference by histological type or prognostic factors. CONCLUSION: Somatostatin receptor scintigraphy does not appear to be sensitive enough to evaluate axillary node extension of breast cancer or even to confirm the presence of tumoral tissue, and this whatever the administration route for (111)In-pentetreotide.

Imaging radiation induced muscular necrosis with antimyosin-scintigraphy and computed tomography.

Radiations accidents involving high exposures require accurate assessment of radiation dose for correct surgical or medical management. Techniques involving computed tomography and antimyosin-antibody scintigraphy were evaluated in an experimental model of acute localized irradiation overexposure to 192Ir. Ten rabbits were exposed to a single dose of 192Ir gamma irradiation (120 Gy) on the back (right iliospinal muscle). Computed tomography and antimyosin-antibody scintigraphy results were compared with those in four control animals. Planar scintiscans (posterior views) were performed 48 h post-injection of antimyosin-antibody each week for 2 mo after exposure. An antimyosin uptake was observed in irradiated muscle five weeks after exposure and correlated with computed tomography and histopathology results, showing muscle necrosis. Biodistribution assessed at 7 and 9 wk post exposure confirmed antimyosin-antibody accumulation in damaged muscle. A semi-quantitative analysis of a region of interest over the uptake area in the irradiated muscle (on the right side) and a contralateral non-irradiated region of interest used as control showed that uptake was significantly higher in irradiated animals than in control animals (p < 0.02). Antimyosin-antibody scintiscans used in nuclear cardiology to explore ischemic heart disease, myocarditis or heart transplant rejection could be realized to assess the extent of muscle necrosis after trauma or radiation induced injury.