FDG Positron Emission Tomography Scans Research Articles

Apoptotic and anti-vascular activity of imatinib in GIST patients

9001 Imatinib mesylate (IM) is a potent inhibitor of the Kit/platelet-derived growth factor receptor(PDGFR) tyrosine kinases. We are investigating the early mechanisms of anti-tumor activity of IM in GIST patients(pts) as measured by 18-fluorodeoxyglucose(FDG) positron emission tomography(PET) imaging. We hypothesize that early reductions in GIST FDG avidity after IM therapy are due to induction of tumor cell apoptosis and anti-vascular activity. Pts with planned resection of their GIST were treated with IM(600 mg/day) preoperatively. Perfusion computed tomography(CT) and FDG PET scans were performed before and after IM therapy for 3, 5, or 7 days. All pts underwent pre-IM biopsy followed by resection no more than 6 hours after completion of IM therapy. CT perfusion parameters included blood flow(BF) and blood volume(BV) of the whole tumor. PET imaging was used to assess the maximum standardized uptake value(SUV) of FDG. Paired tumor biopsies and resected tumors were examined using immunofluorescent laser scanning cytometry to quantify endothelial and tumor cell apoptosis, microvessel density(MVD), phospho-Kit and phospho-PDGFR. 10 GIST pts underwent PET, 7 had a decrease in SUV of greater than 30% while 3 had no decrease or no baseline FDG avidity. The PET responders had a decrease while non-responders had an increase in BF (-37.8% vs. +38.5%, P=.02). PET responders had a decrease in BV compared to the increase seen in non-responders (-29.5% vs +24%, P=.04). 4 responders to IM had a decrease in phospho-Kit in the tumor-associated endothelium(avg. -45%, P=.07) and tumor cell compartment(avg -52%, P=.13). These tumors displayed a 7-fold (P=.08) and 2.8 fold (P=.23) increase in endothelial and tumor cell death, respectively, and a 36% reduction in MVD after IM. The tumor with reduction in BF(-74%) and BV(-61%) displayed the greatest increase in endothelial cell death(.05% to 11%, p<0.05). The most significant reduction in MVD(-78%, P<.05) was observed in the tumor with the greatest reduction in FDG uptake(-85%). IM induces tumor cell apoptosis after brief IM therapy and may have anti-vascular effects on GISTs. We believe that inhibition of Kit activation in the tumor-associated endothelium by IM is a novel finding. No significant financial relationships to disclose.

18F]fluoro-2-deoxy-d-glucose ([18F]FDG) positron emission tomography imaging of thymic carcinoid tumor presenting with recurrent Cushing’s syndrome

We report a case of a young woman with Cushing's syndrome (CS), in whom although endocrine investigations and negative pituitary imaging were suggestive of ectopic ACTH secretion, the results of inferior petrosal sinus (IPS) sampling after coricotropin-releasing hormone (CRH) stimulation were suggestive of pituitary ACTH hypersecretion. (111)In-labelled octreotide and high-resolution computer tomography (CT) revealed a lesion possibly responsible for the ACTH source in the thymus. Thymectomy confirmed concomitant ectopic CRH and probable ACTH production by a thymic neuroendocrine carcinoma. After an 8-year remission period the patient developed a clinical and biochemical relapse. A high-resolution computed tomography (CT) scan of the thorax showed a 2-cm nodule in the thymic bed, which was positive on a [(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) positron emission tomography (PET) scan. However, a repeated thymectomy did not result in remission. A repeat [(18)F]FDG PET study showed persistent disease in the thymic bed and also uptake in the adrenals. The patient underwent bilateral adrenalectomy, which resulted in clinical remission. A further [(18)F]FDG PET scan 8 months later showed no progression of the thymic tumor and confirmed complete excision of the adrenals. This is a rare case of concomitant CRH and ACTH secretion from a thymic carcinoid tumor; the case illustrates the usefulness of functional imaging with [(18)F]FDG PET in the diagnosis, management and follow-up of neuroendocrine tumors.

Stereotactic hypofractionated radiation therapy for stage I non-small cell lung cancer

We reviewed our initial institutional experience with the use of stereotactic hypofractionated radiation therapy (SFRT) in patients with stage I non-small cell lung cancer (NSCLC). Thirty patients with inoperable stage I non-small cell lung cancer due to a severe chronic obstructive pulmonary disease (COPD) and/or chronic heart disease (Eastern Cooperative Oncology Group (ECOG) performance status of 0-2) were treated between December 2000 and October 2003 with SFRT in curative intent. Infiltration of locoregional lymph nodes and distant metastases were ruled out by computerized tomography (CT) scan of the brain, thorax, and abdomen, and by whole body FDG-positron emission tomography scan in all patients. Total RT doses ranged from 24.0 to 37.5 Gy, given in 3-5 fractions to the 60% isodose encompassing the planning target volume. Immobilization was carried out by a vacuum couch and a low-pressure foil. The clinical target volume was the tumor as it appeared in lung windowing on lung CT scan. Organ movements (caused by breathing; range, 6-22 mm) and reproducibility of patient positioning in the couch (range, 3-12 mm) were calculated by sequential CT and orthogonal films. The individual values were taken into account as a safety margin for the definition of the planning target volume (PTV). The median follow-up of living patients is 18 months (range, 6-38 months). As maximum response, there were 10 (33%) complete responses (CRs) and 14 (47%) partial responses (PRs), resulting in a total response rate of 80%. Stable disease was observed in 6 (20%) patients, while no patient experienced progressive disease. During follow-up, 2 (7%) local recurrences were observed (after 17 and 18 months, respectively). Of 5 (17%) patients who developed distant metastasis, 1 patient developed it in liver (3 months), another one in brain (6 months), and another one in the lung (36 months), while 2 patients developed it in mediastinal lymph nodes (after 8, and 11 months, respectively) only. Of 9 (30%) patients who have died, only 3 (10%) died of cancer, while 6 (20%) died of cancer-unrelated or unknown causes. Acute side effects were mild and affected 9 (33%) patients during the RT course (fatigue being the most frequent one in 6 patients). There were 22 acute events occurring in 19 (63%) patients during the first 3 months post-SFRT, the most frequent one being pneumonitis observed in 14 (46%) patients. However, there was only one (3%) grade 3 acute toxicity and no patient experienced greater than grade 3 toxicity during this study. One (3%) patient experienced rib fracture as the late event. SFRT is a feasible and safe treatment method in inoperable patients with stage I NSCLC having reduced lung capacity. Longer follow-up is necessary to get robust data on late toxicity as well as survival.

Rapid Response to Treatment of Multiple Myeloma Detected with FDG PET Scanning in Multiple Myeloma - Early Results from Total Therapy III.

Fluorodeoxyglucose Positron Emission Tomography (PET) scanning can rapidly detect and quantify changes in tumor metabolism. We present early results from the first 47 patients enrolled in Total Therapy III for multiple myeloma using PET scanning and correlating with serum M protein. Since we have previously demonstrated that diffuse uptake patterns do not have prognostic significance, we have limited our assessment of these 47 patients to those with one or more PET-defined focal lesions (FL) at baseline who have had at least one follow-up PET scan (25 patients). Of this group of 25, 10 have had a second follow-up scan. These whole body PET scans were performed at baseline and at time points corresponding to immediately after two cycles of VDT-PACE, landmarks LMK1 and LMK2. Patients with complete resolution of FL on PET are considered to be in PET-CR. We find that 17/25 (68%) had a decrease in number of FL from baseline to LMK1 and 8/10 (80%) had a decrease in number of FL from baseline to LMK2. In addition, 6/25 (24%) were in PET-CR by LMK1 and 3/10 (30%) in PET-CR by LMK2. Similarly, a decrease in serum M-protein was seen in 16/25 (64%) from baseline to LMK1 and in 8/10 (80%) from baseline to LMK2.At baseline, 10 patients had serum M protein levels of 0.01 g/dl or less. Of these, 8 (80%) had PET-defined focal lesions, demonstrating PET's ability to monitor tumor metabolism in the face of hypo- or non-secretory disease. Of these, 7 have been enrolled sufficient time to have a second PET scan, with 6/7 (86%) demonstrating a continuing decrease in number of FL in response to treatment. At baseline, PET detected 5 of 47 patients with extramedullary disease (EMD), a finding of severe adverse prognostic significance at baseline. Of these patients, all had FL at baseline PET and all had decreasing number of FL on first follow-up PET scan (two have had a second follow-up scan, one improving and one PET-CR). One of these patients with EMD is nonsecretory.From these data, we conclude that functional imaging with PET scanning offers important and unique information about early tumor response that improves patient management by demonstrating rapid change in response to treatment that not only parallels serum M-protein response but which also is reliable in hypo- or non-secretory disease as well as in detection and monitoring of extramedullary tumor, an ominous condition that is particularly difficult to detect in the hypo- or non-secretory patient.

Short Communication: 18F-FDG PET Early After Radiotherapy in Lymphoma Patients

The aim of this study was to evaluate the rate of postactinic inflammatory alterations that could lead to false-positive results in FDG-PET images, in a group of lymphoma patients studied with positron emission tomography (PET) early after the end of radiation therapy.Sixteen (16) consecutive patients were referred to our center for malignant lymphoma; 14 of 16 patients had a mediastinal bulky mass at diagnosis. Each patient underwent chemotherapy and then radiotherapy (RT): for clinical reasons, shortly after RT (range, 25-56 days; mean, 38.7 days) a FDG PET scan was required to evaluate the effect of therapy. We intravenously injected 370 MBq of 18F-FDG, and after 60-90 minutes we recorded images.Despite a relatively short time after RT, there was no pathological tracer uptake in 13 of 16 patients. In 3 cases, a mild increase in FDG uptake was observed, but no findings which would lead to a false-positive diagnosis. In 2 of 3 cases, postactinic pneumopathy was diagnosed (PET scan performed 51 and 52 days after RT); while in 1 patient, soft-tissue inflammation was present (PET scan performed 42 days after RT).Our data indicates that the rate of postactinic PET inflammatory alterations in lymphoma patients is not very high and appear to be not strictly linked to the elapsed time since the end of RT treatment.

18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer.

To prospectively evaluate the effect of adding whole-body (18)F-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) to conventional screening for distant metastases in patients with locally advanced breast cancer (LABC). All women with LABC referred for participation in the LABC Spinoza trial were considered eligible for this study. Patients were included if chest x-ray, bone scan, liver ultrasound, or computed tomography scan performed by the referring physician failed to reveal distant metastases. They underwent whole-body FDG PET scanning before therapy. Patients with subsequently proven distant metastases were switched to alternative forms of chemotherapy, hormonal therapy, or both. Among the 48 patients evaluated with PET, 14 had abnormal FDG uptake, and metastases were suspected in 12. After simple clinical evaluation (plain x-ray, history), 10 sites that were suggestive of abnormality remained. Further work-up revealed that four sites were metastases. Proven false positivity occurred in one patient with sarcoidosis. In the other five patients, the reason for abnormal FDG uptake (liver, lung, bone) remained unclear, and patients were treated as planned. Eleven months later, distant metastases were found in one patient at sites unrelated to the previous FDG uptake. The addition of FDG PET to the standard work-up of patients with LABC may lead to the detection of unexpected distant metastases. This may contribute to a more realistic stratification between patients with true stage III breast cancer and those who are in fact suffering from stage IV disease. Abnormal PET findings should be confirmed to prevent patients from being denied appropriate treatment.

P-429 FDG-positron emission tomography scanning(PET) in the staging and monitoring of small cell lung cancer(SCLC)

P-429 FDG-positron emission tomography scanning(PET) in the staging and monitoring of small cell lung cancer(SCLC)

Fluorodeoxyglucose positron emission tomography studies in diagnosis and staging of clinically organ-confined prostate cancer

Objectives. To determine the value of 18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) studies in the evaluation of patients with organ-confined prostate cancer. This imaging method has previously found little usefulness in localized prostate tumors because of excretion of the isotope into the urine, masking any lower urinary tract lesions. We evaluated this imaging modality using hydration, furosemide, and bladder emptying before the procedure to evacuate the nonspecific isotope in the urine. Methods. FDG PET scans were performed on 24 patients diagnosed with clinically organ-confined prostate cancer. No patient had received any prior treatments for the cancer. FDG PET scans were performed 1 hour after injection of 15 mCi of F-18 deoxyglucose. Patients were scanned from the base of the skull through the inguinal region (including the pelvis). Additional signal attenuation-corrected images of the inguinal region were acquired 30 minutes after intravenous injection of 40 mg of furosemide. The final diagnosis was made by histologic examination, correlative imaging studies, and/or clinical follow-up. Results. FDG PET studies were negative in 23 of the 24 organ-confined prostate cancers and the study was only faintly positive in 1 tumor (4.0% sensitivity). Conclusions. FDG PET is not a useful test in the evaluation of clinically organ-confined prostate cancer.

Positron emission tomography scanning in malignant melanoma

Several recent studies have demonstrated the low yield of anatomically based computed tomography scans in evaluating Stage III (American Joint Committee on Cancer) patients with malignant melanoma. The purpose of this study was to investigate the efficacy and clinical utility of functionally based positron emission tomography (PET) scans in the same patient population. A prospective evaluation of 106 whole body PET scans obtained after injection of 2-fluorine-18, 2-fluoro-2-deoxy-D-glucose (FDG) was performed in 95 patients with clinically evident Stage III lymph node and/or in-transit melanoma. Areas of abnormality on FDG PET scanning were identified visually as foci of increased metabolic activity compared with background, and all positive foci were assessed pathologically. In this patient population, there were 234 areas that were evaluated pathologically of which 165 were confirmed histologically to be melanoma. PET scanning identified 144 of the 165 areas of melanoma for a sensitivity of 87.3%. The 21 areas of melanoma that were missed included 10 microscopic foci, 9 foci less than 1 cm, and 2 foci greater than 1 cm. There were 39 areas of increased PET activity that were not associated with malignancy for a 78.6% predictive value of a positive test. Of the 39 false-positive areas (false-positive rate of 56.5%), 13 could be attributed to recent surgery, 3 to arthritis, 3 to infection, 2 to superficial phlebitis, 1 to a benign skin nevus, and 1 to a colonic polyp. Pathologic evaluation of the remaining false-positive areas failed to reveal a definitive etiology for their increased activity on PET scan. With the application of pertinent clinical information, the predictive value of a positive PET scan could be improved to 90. 6%. The specificity of PET scanning in this study was only 43.5% because very few prophylactic lymph node dissections were performed. Thirty-six of the total 183 abnormal areas (19.7%) on PET scanning proved to be unsuspected areas of metastatic disease. These findings led to a change in the planned clinical management in patients after 16 of the 106 PET scans (15.1%). FDG PET scanning can be helpful in managing patients with Stage III melanoma in whom further surgery is contemplated. Although false-positive areas are not uncommon, PET scans did change the management of patients 15% of the time. PET's inability to identify microscopic disease suggests that it is of limited use in evaluating patients with Stage I-II disease.

Incidental second primary in the breast detected by F-18 FDG positron emission tomography scan.

A 39-year-old women had multiple lung lesions on a follow-up chest radiograph after laparotomy and left cystectomy for an immature ovarian teratoma. Results of a work-up for metastases were normal, including beta human chorionic gonadotrophin and alpha-fetoprotein levels. An F-18 FDG positron emission tomographic (PET) whole-body scan performed to evaluate the possibility of pulmonary metastases showed no abnormality in the chest or pelvis. There was intense focal uptake in the left breast, however, suggesting an incidental second malignancy. Pathologic evaluation of the left breast mass showed infiltrating ductal cell carcinoma, for which she received chemotherapy. Histologic examination of the lung lesions showed a benign mature teratoma in one nodule and fibrosis in several of the others. In a patient with a neoplasm, F-18 FDG uptake on a whole-body scan may be unrelated to the primary tumor and could represent an incidental second malignancy.

Localized form of bronchioloalveolar carcinoma: FDG PET findings.

The aim of our study was to describe 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) findings of a localized form of bronchioloalveolar carcinoma and to compare those findings with other cell types of lung cancer. FDG PET was performed in 48 patients with lung cancer. The patients had carcinomas of various cell types: bronchioloalveolar carcinoma (n = 9), squamous cell carcinoma (n = 11), adenocarcinoma (n = 22), and other cell types (n = 6). Using FDG PET, we compared peak standardized uptake values among the various cell types of lung cancer. CT and pathologic findings for patients with bronchioloalveolar carcinoma were also reviewed. Overall, 48 malignant tumors showed a mean peak standardized uptake value of 8.0 +/- 4.1. The mean peak standardized uptake value was 3.5 +/- 2.2 for bronchioloalveolar carcinoma, 10.8 +/- 4.4 for squamous cell carcinoma, and 8.8 +/- 3.2 for adenocarcinoma. The mean peak standardized uptake value for bronchioloalveolar carcinoma was significantly lower than that for adenocarcinoma and squamous cell carcinoma (p < .001). On high-resolution CT scans, bronchioloalveolar carcinomas appeared as areas of ground-glass opacity (n = 4), as nodules (n = 2), as masses (n = 2), and as a ground-glass opacity plus consolidation (n = 1). On pathologic examination, bronchioloalveolar carcinomas were well differentiated, having moderate degrees of nuclear atypism, mild degrees of mitotic figure, desmoplasia, and necrosis. The localized form of bronchioloalveolar carcinoma shows significantly lower peak standardized uptake values than do other lung carcinomas. Thus, bronchioloalveolar carcinoma can be a potential cause of false-negative findings of malignancy on FDG PET scans. When bronchioloalveolar carcinoma is suggested, FDG PET results should be interpreted in combination with high-resolution CT findings.

Vulnerability to tardive dyskinesia development in schizophrenia: An FDG-PET study of cerebral metabolism

An understanding of the development of tardive dyskinesia (TD) may require prospective studies assessing the relationship of brain function measures to behavior. This study was undertaken to determine whether predisposition to the development of TD is related to abnormalities of cerebral 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) measures in schizophrenia. A group of 42 patients without TD underwent FDG PET scanning for measuring cerebral metabolism as well as neuropsychological evaluation and magnetic resonance imaging. Patients were assessed longitudinally for TD development. Eight patients developed TD within 3 years. They were matched to eight patients without TD. Glucose metabolic rates and region/ whole brain ratios were examined in 38 regions of interest per hemisphere. Whole brain metabolism did not differ between the two groups. However, relative hypermetabolism in temporolimbic, brainstem, and cerebellar regions and hypoactivity in parietal and cingulate gyrus were found in the patients who later developed TD in contrast to those who did not. The groups were matched on clinical measures and had similar neuropsychological and neuroanatomic testing results. Thus, differences in the metabolic activity of specific brain regions are associated with vulnerability to TD development.

Positron emission tomography to stage suspected metastatic colorectal carcinoma to the liver

Accurate detection of recurrent colorectal carcinoma remains a clinical challenge. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (18FDG) is an imaging technique that allows direct evaluation of cellular metabolism. 18F-fluorodeoxyglucose PET was compared to computed tomography (CT) and CT portography for staging metastatic colorectal carcinoma. Twenty-four patients previously treated for colorectal carcinoma who had suspected recurrence to the liver underwent an 18FDG PET scan of the entire body. All patients had either a CT scan of the abdomen (n = 17), a CT portogram (n = 18), or both (n = 11). The final diagnosis was obtained by tissue pathology in 19 patients and clinical follow-up in 5 patients. A total of 60 suspicious lesions were identified. Of the 55 intrahepatic lesions, 39 were malignant and 16 were benign. Of the 5 extra-hepatic lesions, 4 were malignant. The 18FDG PET imaging had a higher accuracy (93%) than CT and CT portography (both 76%) in detecting metastatic disease to the liver, and detected unsuspected extrahepatic recurrence in 4 patients. Although the sensitivity of 18FDG PET (90%) was slightly lower than that of CT portography (97%), the specificity was much higher (100% versus 9%), including postsurgical sites. 18FDG PET altered surgical plans in 6 (25%) of 24 patients. 18FDG PET is extremely useful in staging patients with suspected metastatic colorectal carcinoma to the liver.

Identification of early recurrence of primary central nervous system tumors by [18F]fluorodeoxyglucose positron emission tomography

As aggressive neurosurgery and adjuvant therapy have become standard care for most patients with primary central nervous system (CNS) tumors, limitations of posttreatment neuroimaging techniques have become more apparent. Interpretation of computed cranial tomography (CT) and magnetic resonance imaging (MRI) in patients with brain tumors is complicated by changes related to surgery, corticosteroids, radiation, and chemotherapy. We investigated the role of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (FDG-PET) in these difficult diagnostic situations by obtaining FDG-PET scans in 5 patients following temporal lobectomy for epilepsy, in 5 patients with recurrent anaplastic gliomas before and after corticosteroid therapy, and in 5 patients after the development of histologically confirmed radionecrosis. We also obtained postoperative FDG-PET scans in 32 consecutive patients undergoing initial resection of a primary brain tumor. Our results indicate that glucose uptake as detected by FDG-PET scanning with [18F]fluorodeoxyglucose is not increased in the postoperative period; is not affected by steroid therapy; and accurately predicts early recurrence of tumor, supplementing other predictors of tumor behavior, including extent of resection, histological diagnosis, and postoperative CT. Thus PET using [18F]fluorodeoxyglucose can contribute to the optimum management of patients with primary brain tumors.