Neoadjuvant FOLFIRI+bevacizumab in patients with resectable liver metastases from colorectal cancer: a phase 2 trial.

BACKGROUND: Preoperative treatment of resectable liver metastases from colorectal cancer (CRC) is a matter of debate. The aim of this study was to assess the feasibility and activity of bevacizumab plus FOLFIRI in this setting. METHODS: Patients aged 18-75 years, PS 0-1, with resectable liver-confined metastases from CRC were eligible. They received bevacizumab 5 mg kg(-1) followed by irinotecan 180 mg m(-)(2), leucovorin 200 mg m(-)(2), 5-fluorouracil 400 mg m(-)(2) bolus and 5-fluorouracil 2400 mg m(-)(2) 46-h infusion, biweekly, for 7 cycles. Bevacizumab was stopped at cycle 6. A single-stage, single-arm phase 2 study design was applied with 1-year progression-free rate as the primary end point, and 39 patients required. RESULTS: From October 2007 to December 2009, 39 patients were enrolled in a single institution. Objective response rate was 66.7% (95% exact CI: 49.8-80.9). Of these, 37 patients (94.9%) underwent surgery, with a R0 rate of 84.6%. Five patients had a pathological complete remission (14%). Out of 37 patients, 16 (43.2%) had at least one surgical complication (most frequently biloma). At 1 year of follow-up, 24 patients were alive and free from disease progression (61.6%, 95% CI: 44.6-76.6). Median PFS and OS were 14 (95% CI: 11-24) and 38 (95% CI: 28-NA) months, respectively. CONCLUSION: Preoperative treatment of patients with resectable liver metastases from CRC with bevacizumab plus FOLFIRI is feasible, but further studies are needed to define its clinical relevance.

Feasibility of bremsstrahlung dosimetry for direct dose estimation in patients undergoing treatment with 90Y-ibritumomab tiuxetan.

PURPOSE: Radioimmunotherapy with (90)Y-ibritumomab tiuxetan has been used successfully used in the treatment of CD20-positive non-Hodgkin's lymphoma (NHL). Pretherapy imaging with (111)In-ibritumomab tiuxetan has been used in provisional dosimetry studies. Posttherapy imaging of (90)Y-ibritumomab tiuxetan for clinical use is appealing as it would simplify the data acquisition process and allow measurements of actual doses absorbed during treatment. METHODS: The study included 29 patients with non-Hodgkin's lymphoma, of whom 16 (group I) received a pretherapy (111)In-ibritumomab tiuxetan diagnostic study and (90)Y-ibritumomab tiuxetan treatment 1 week later, and 13 (group II) received only (90)Y-ibritumomab tiuxetan treatment. Planar imaging and blood sampling were performed in all patients. The doses absorbed by organs at risk were calculated using a whole-body average attenuation correction factor (relative dosimetry approach) and, in the case of the (111)In-ibritumomab tiuxetan image sets, also using organ-specific attenuation correction factors (absolute dosimetry method). Red marrow absorbed doses were based on gamma counting of blood samples. RESULTS: The estimated red marrow absorbed doses from (111)In and (90)Y data were equivalent. In all cases, the doses absorbed by organs at risk were found to be within prescribed limits. The relative dosimetry approach applied to both the (90)Y and (111)In data significantly underestimated the doses relative to those obtained with the (111)In absolute dosimetry method which is generally accepted as the reference method (MIRD 16). In the case of (111)In, the relative dosimetry approach values were highly correlated (R(2) = 0.61) with the reference method values. Relative dosimetry estimates may be adjusted multiplying by a correction factor of 2.8. The (90)Y-ibritumomab tiuxetan relative dosimetry data correlated poorly with the reference method values (R (2) = 0.02). CONCLUSION: Based on patient-specific dosimetry, the administered activity may be increased by an average factor of 2.4, indicating that most patients could be undertreated. The relative dosimetry approach based on planar imaging largely underestimates doses relative to reference values. Dosimetry based on planar bremsstrahlung imaging is not a dependable alternative to (111)In dosimetry.

18F-FDG positron autoradiography with a particle counting silicon pixel detector.

We report on tests of a room-temperature particle counting silicon pixel detector of the Medipix2 series as the detector unit of a positron autoradiography (AR) system, for samples labelled with (18)F-FDG radiopharmaceutical used in PET studies. The silicon detector (1.98 cm(2) sensitive area, 300 microm thick) has high intrinsic resolution (55 microm pitch) and works by counting all hits in a pixel above a certain energy threshold. The present work extends the detector characterization with (18)F-FDG of a previous paper. We analysed the system's linearity, dynamic range, sensitivity, background count rate, noise, and its imaging performance on biological samples. Tests have been performed in the laboratory with (18)F-FDG drops (37-37 000 Bq initial activity) and ex vivo in a rat injected with 88.8 MBq of (18)F-FDG. Particles interacting in the detector volume produced a hit in a cluster of pixels whose mean size was 4.3 pixels/event at 11 keV threshold and 2.2 pixels/event at 37 keV threshold. Results show a sensitivity for beta(+) of 0.377 cps Bq(-1), a dynamic range of at least five orders of magnitude and a lower detection limit of 0.0015 Bq mm(-2). Real-time (18)F-FDG positron AR images have been obtained in 500-1000 s exposure time of thin (10-20 microm) slices of a rat brain and compared with 20 h film autoradiography of adjacent slices. The analysis of the image contrast and signal-to-noise ratio in a rat brain slice indicated that Poisson noise-limited imaging can be approached in short (e.g. 100 s) exposures, with approximately 100 Bq slice activity, and that the silicon pixel detector produced a higher image quality than film-based AR.

Design, synthesis and preclinical evaluation of radiolabeled peptides for diagnosis and therapy.

Recent years have seen an increased effort in the development of peptide based radiopharmaceuticals for nuclear medicine applications in imaging and therapy. This field is of particular interest in the development of new cancer imaging and treatment strategies. Major developments in the molecular biology of cancer have brought forth the discovery of a number of receptor systems and other cell surface molecules that can be utilized as molecular targets for peptide based agents. Although such a strategy is very appealing and shows great potential for application in humans, there are as yet very few radiopharmaceuticals developed based on this scheme that have made it into clinical practice. Many different factors contribute to the generation of a successful radiopharmaceutical. Among these, a thorough and efficient pre-clinical evaluation process is necessary to single out those lead compounds that show more promise and are most likely to be winners in clinical applications. To maximize the efficacy of pre-clinical testing one must utilize currently available technology to the best extent possible. Expertise in different areas of drug development is indispensable for this type of research. This work will analyze currently available methods utilized to evaluate radiopharmaceuticals being developed, from compound design to evaluation in pre-clinical animal models.

In vitro and in vivo characterization of Indium-111 and Technetium-99m labeled CCK-8 derivatives for CCK-B receptor imaging.

Cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with 111In or 99mTc for CCK-B receptor imaging. Derivatives of CCK8 were obtained by addition at the N-terminus in solid phase of a DTPA derivative (DTPAGlu) linked through a glycine spacer (DTPAGlu-G-CCK8) or cysteine, glycine and a diphenylphosphinopropionyl moiety (PhosGC-CCK8) for labeling with 111In and 99mTc, respectively. CCK-BR overexpressing A431 cancer cell lines were utilized to characterize in vitro properties of the two compounds as well as for generating xenografts in nude mice for in vivo characterization. Both 111In-DTPAGlu-G-CCK8 and 99mTcPhosGC-CCK8 showed similar binding affinities for CCK-BR with dissociation constants of 20-40 nM, were internalized after interaction with the receptor and displayed prolonged cellular retention times. Specific in vivo interaction with the receptor of both CCK8 analogs was observed in our animal model. 111In-DTPAGlu-G-CCK8 showed better target to non-target ratios, although it appeared to be rapidly metabolized after injection and activity cleared through the kidneys. 99mTc-PhosGC-CCK8 was more stable in vivo but showed marked hepatobiliary clearance with resulting high background activity in the bowel. The rapid clearance and lower background obtained with 111In-DTPAGlu-G-CCK8 make this a better candidate for further development.

MIBI as prognostic factor in breast cancer.

Evaluation of treatment response is of primary importance in the management of patients with cancer. Both positron- and g-emitting compounds have been used to monitor changes in tumor metabolism or viability after therapy. The use of (99m)Tc-labeled lipophilic cations raised the possibility to predict the tumor response to treatment and to identify patients who will become refractory to subsequent therapy. In particular, many studies have shown the prognostic value of (99m)Tc-MIBI scan in different types of malignancy including breast and lung cancer, lymphoma and sarcoma. The ability of (99m)Tc-MIBI to interact with P-glycoprotein, allowing the functional assessment of the multidrug resistant phenotype, is one of the mechanisms underlying its prognostic value. Additional mechanisms of cell resistance, mainly involving alterations of apoptosis, may affect (99m)Tc-MIBI uptake in tumors. Therefore, either an enhanced tracer clearance or a reduced early uptake of (99m)Tc-MIBI indicate a poor response to therapy. In both cases, (99m)Tc-MIBI scan may ensure that the further management strategy will be effective in individual cancer patients.

Monitoring the correction of glycogen storage disease type 1a in a mouse model using [(18)F]FDG and a dedicated animal scanner.

Monitoring gene therapy of glycogen storage disease type 1a in a mouse model was achieved using [(18)F]FDG and a dedicated animal scanner. The G6Pase knockout (KO) mice were compared to the same mice after infusion with a recombinant adenovirus containing the murine G6Pase gene (Ad-mG6Pase). Serial images of the same mouse before and after therapy were obtained and compared with wild-type (WT) mice of the same strain to determine the uptake and retention of [(18)F]FDG in the liver. Image data were acquired from heart, blood pool and liver for twenty minutes after injection of [(18)F]FDG. The retention of [(18)F]FDG was lower for the WT mice compared to the KO mice. The mice treated with adenovirus-mediated gene therapy had retention similar to that found in age-matched WT mice. These studies show that FDG can be used to monitor the G6Pase concentration in liver of WT mice as compared to G6Pase KO mice. In these mice, gene therapy returned the liver function to that found in age matched WT controls as measured by the FDG kinetics in the liver compared to that found in age matched wild type controls.

Radiolabeling approaches for cholecystokinin B receptor imaging.

Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging. In particular, cholecystokinin (CCK) receptors of the subtype B (CCK-BR) have been shown to be overexpressed in certain neuroendocrine tumors including medullary thyroid cancer. Our recent work has focused on new methods to radiolabel the CCK8 peptide with (111)In or (99m)Tc for the purpose of developing radiopharmaceuticals for in vivo CCK-B receptor imaging. Labeling of CCK8 with (111)In was achieved at the N-terminus of the peptide by adding, in solid phase, a glutamate coupled diethylenetriaminepentaacetic acid (DTPA) moiety through a glycine linker, yielding DTPA-Glu-G-CCK8. For labeling with (99m)Tc, the CCK8 peptide was modified at its N-terminus by introducing, in the following order--cysteine, glycine, and a diphenylphosphinopropionyl moiety--giving a 10-residue peptide derivative, Phos-GC-CCK8. A cell culture model was developed for the purpose of evaluating the binding properties of these two ligands. The human epidermoid carcinoma cell line, A431, was transfected with a plasmid containing the full coding sequence of the human CCK-BR under a strong viral promoter, obtaining a number of receptors in the range of 2-5 x 10(6) per cell. Control cells were transfected with vector alone. An animal tumor model utilizing these two cell lines was developed to evaluate the specificity of interaction with the CCK-BR and biodistribution properties of the compounds. CCK-BR positive and control cells were subcutaneously injected in opposite flanks of CD1 female nude mice in order to obtain xenografts differing only in their ability to express CCK-B receptors. High performance liquid chromatography (HPLC) and other chromatographic methods were utilized to assess stability of the radiolabeled compounds after injection. Both (111)In-DTPA-Glu-G-CCK8 and (99m)Tc-Phos-GC-CCK8 showed similar binding affinities for cultured CCK-BR expressing cells, with dissociation constants in the range of 20-40 nM. With the two xenograft approach, we were able to demonstrate specific interaction with the receptor of both CCK analogs in our animal model. The data obtained shows rapid specific localization of both compounds on the CCK-BR overexpressing xenografts. Both tracers show rapid plasma clearance of unbound peptide. Clearance of (111)In-DTPA-Glu-G-CCK8 appears to be preferentially through the kidneys, whereas (99m)Tc-Phos-GC-CCK8 clearance occurs both through kidneys and the hepatobiliary system. Both our labeling approaches appear adequate for clinical use of peptide based radiopharmaceuticals, although (99m)Tc-Phos-GC-CCK8 shows elevated accumulation in the gastrointestinal tract, which causes high background activity.

Cellular release of [18F]2-fluoro-2-deoxyglucose as a function of the glucose-6-phosphatase enzyme system.

[(18)F]-2-Fluoro-2-deoxyglucose (FDG) is a glucose analog currently utilized for positron emission tomography imaging studies in humans. FDG taken up by the liver is rapidly released. This property is attributed to elevated glucose-6-phosphatase (Glc-6-Pase) activity. To characterize this issue we studied the relationship between Glc-6-Pase activity and FDG release kinetics in a cell culture system. We overexpressed the Glc-6-Pase catalytic unit in a Glc-6-Pase-deficient mouse hepatocyte (Ho-15) and in A431 tumor cell lines. Glc-6-Pase enzyme activity and FDG release rates were determined in cells transfected with the Glc-6-Pase gene (Ho-15-D3 and A431-AC3), in mock-transfected cells of both cell lines, and in wild-type mouse hepatocytes (WT10) as control. Although the highest level of Glc-6-Pase activity was measured in A431-AC3, Ho-15-D3 cells showed much faster FDG release rates. The faster FDG release correlated with the level of glucose 6-phosphate transporter (Glc-6-PT) mRNA, which was found to be expressed at higher levels in Ho-15 compared with A431 cells. Overexpression of Glc-6-PT in A431-AC3 produced a dramatic increase in FDG release compared with control cells. This study gives the first direct evidence that activity of the Glc-6-Pase complex can be quantified in vivo by measuring FDG release. Adequate levels of Glc-6-Pase catalytic unit and Glc-6-PT are required for this function. FDG-positron emission tomography may be utilized to evaluate functional status of the Glc-6-Pase complex.

Targeting of transferrin receptors in nude mice bearing A431 and LS174T xenografts with [18F]holo-transferrin: permeability and receptor dependence.

UNLABELLED: The goal of this study was to investigate whether 18F-labeled transferrin (Tf), which has a molecular weight (Mr) of approximately 79,000, binds to Tf receptor sites in tumors in a specific manner within the time frame commensurate with the half-life of 18F (109.7 min). We have previously shown that [18F]holo-Tf ([18F]Tf) maintains all properties of native Tf in vitro and that it can specifically target liver Tf receptor sites in vivo. METHODS: The distribution of [18F]Tf, using [18F]albumin (Alb) or [14C]Alb as a control, was studied over a 6-h period in nude mice bearing LS174T and A431 xenografts of a high- and low-permeability tumor, respectively. RESULTS: Measurements of Tf receptor concentration in the tumor extracts suggest similar binding capacities. In vivo, liver uptake values were higher for [18F]Tf than for both [18F]Alb and [14C]Alb throughout the study, indicating specific binding. In contrast, tumor Tf uptake values remained below those of the Alb tracers, and tumor-to-blood ratios of [18F]Tf in each xenograft increased in parallel with those of the Alb tracers. The permeabilities of [14C]Alb and [18F]Tf in LS174T were calculated to be 1.29+/-0.49 and 1.03+/-0.38 microL/min/g (mean +/- SD), respectively, whereas the permeabilities of the two tracers in A431 were 0.79+/-0.24 and 0.44+/-0.04 microL/min/g. Pharmacokinetic modeling of the data using these permeabilities and the high plasma and extracellular concentrations of endogenous Tf showed that the observed uptake values in the two xenografts are consistent with a non-receptor-mediated distribution. In the liver, the absence of permeability barriers yields specific [18F]Tf binding to receptors compared with the [14C]Alb control, within 5 min after injection. CONCLUSION: Receptor-mediated accumulation of [18F]Tf in tumor xenografts is impaired by rate-determining permeability and competition from endogenous Tf and is not achieved in a time frame of 6 h.

Glut-1 and hexokinase expression: relationship with 2-fluoro-2-deoxy-D-glucose uptake in A431 and T47D cells in culture.

Uptake of 2-[18F]-2-deoxy-D-glucose (FDG) has been used as a marker of increased glucose metabolism to visualize, stage, and monitor progression of human cancers with positron emission tomography. Many human tumors have been shown to overexpress the Glut-1 glucose transport protein. The aim of this study is to define whether a quantitative relationship exists between the amount of Glut-1 expressed by cells and their ability to accumulate FDG. We characterized the expression of the known facilitative and sodium-dependent glucose transporter isoforms in six different cancer cell lines used in our laboratory (A431, MDA-MB-231, T47D, CaCo II, MCF7, and HepG2). A431 and T47D cells express, respectively, the highest and lowest amount of Glut-1 mRNA by Northern blot of all of the cells analyzed, and no other glucose transporter isoforms were detectable by this method in both cell lines. Both total and plasma membrane-associated Glut-1 protein levels were higher in A431 than in T47D cells, consistent with the higher Glut-1 mRNA levels. However, T47D cells accumulate FDG more rapidly than do A431 cells. 3-O-Methylglucose transport is higher in A431 cells. Although hexokinase I and II mRNA levels are higher in A431 cells than in T47D cells, the ability of mitochondrial preparations to phosphorylate FDG is higher in T47D cells. Our data indicate that in these cultured cells, FDG uptake correlates better with FDG phosphorylating activity of mitochondrial preparations rather than the level of expression of the Glut-1 or hexokinase I and II genes.

The gallium-deferoxamine complex: stability with different deferoxamine concentrations and incubation conditions.

Previous studies report that deferoxamine (DFO) binds metallic ions such as Fe3+, In3+ and Ga3+ with very high affinity. This property of DFO has been utilized to label DFO-coupled compounds with radiometals such as 67Ga and 111In. We have studied the effect of low DFO concentrations and of different incubation conditions on the stability of the 67Ga-DFO complex. In our experience high (> 5 microM) DFO concentration appears to be critical in obtaining high radiochemical purity of such complexes.

Decreased brain glucose utilization in patients with Cushing's disease.

UNLABELLED: Glucocorticoid hormones affect glucose use in different tissues, and the results of several experimental studies have suggested that glucocorticoids have a central action on cerebral metabolism. PET, using the radiotracer 18F-fluorodeoxyglucose (FDG), permits the measurement of cerebral glucose metabolism. METHODS: To investigate whether cerebral glucose metabolism would be altered in patients with increased plasma glucocorticoid levels, we analyzed the FDG PET studies that were done on 13 patients with Cushing's disease and compared the results with those obtained in 13 age-matched normal control subjects. A second FDG PET scan was performed on 4 patients after surgical removal of the pituitary adenoma. RESULTS: Patients with Cushing's disease had a significant reduction in cerebral glucose metabolism compared with normal controls. In the patients on whom a second PET scan was performed, there was a trend toward increased glucose metabolism on the second scan when comparing pre- and postsurgery values for each patient. CONCLUSION: We suggest that the decreased cerebral glucose metabolism we observed in Cushing's disease is attributable to increased glucocorticoid levels, and we speculate that abnormal cerebral glucose metabolism might contribute to the cognitive and psychiatric abnormalities that are frequently observed in patients with Cushing's disease.

White matter lesion detection in multiple sclerosis: improved interobserver concordance with multispectral MRI display.

An assessment of the detectability of white matter lesions and of concordance between observers with different levels of MRI reading experience was performed with comparative evaluation of spin-echo MRI images and of corresponding "multispectral" maps in 16 patients with definite multiple sclerosis (MS). Multispectral maps were obtained by means of a recently described post-processing technique based on the simultaneous display of MRI parameters and a standardized colour scale with red, green and blue coding for relaxation rates R1 and R2 and proton density, respectively. Spin-echo images on films and multispectral maps displayed on a personal computer were randomly rated at 2-month intervals. Interobserver concordance (k-test) was assessed among three readers with different levels of MRI experience (an experienced neuroradiologist, a radiology resident and a neurologist). For multispectral maps we found increased interobserver concordance with the experienced neuroradiologist (multispectral vs conventional images; k = 0.77 vs 0.66 for the radiology resident and 0.66 vs 0.56 for the neurologist), an increased number of detected lesions and decreased reading time. Multispectral maps permit easy detection of MS lesions and may improve interobserver concordance compared with conventional spinecho studies.

Measurement of transferrin receptor kinetics in the baboon liver using dynamic positron emission tomography imaging and [18F]holo-transferrin.

We have evaluated the use of [18F]holo-transferrin ([18F]Tf) and positron emission tomography (PET) to measure in vivo Tf receptor expression and recycling using the baboon liver as a model. [18F]Tf was intravenously injected in three baboons and dynamic PET was performed over the region containing liver and spleen. In two of the three baboons, [18F]albumin ([18F]Alb), labeled with the same technique, was administered 3 hours later. Time activity curves (TACs) were obtained from liver and spleen for both tracers. TACs for [18F]Tf over the liver were fit to a pharmacokinetic model including vascular radioactivity and an extravascular tissue compartment corresponding to transferrin uptake and release. [18F]Alb data provided an independent estimate of plasma volume. Kinetic analysis showed the presence of a tissue compartment for [18F]Tf that rapidly reaches equilibrium (half time 7-10 minutes). In this organ, the measured rates for Tf turnover obtained with quantitative PET are similar to previously published data using cell culture systems. A model for [18F]Tf in the spleen was not statistically improved by adding a tissue compartment. These data and the pharmacokinetic modeling provide in vivo evidence of a high flux equilibrium binding compartment in the liver, consistent with Tf internalization and recycling.

A review of new oncotropic tracers for PET imaging.

We have developed three biochemical probes to determine if they are sensitive probes of early biochemical change in a tumor. All three probes appear to have the appropriate properties for in vivo imaging, but must now be evaluated as probes for the sensitive detection of changes in early malignant disease.

Functional characterization of brain tumors: an overview of the potential clinical value.

Early detection and characterization are still challenging issues in the diagnostic approach to brain tumors. Among functional imaging techniques, a clinical role for positron emission tomography studies with [18F]-fluorodeoxyglucose and for single photon emission computed tomography studies with [201Tl]-thallium-chloride has emerged. The clinical role of magnetic resonance spectroscopy is still being defined, whereas functional magnetic resonance imaging seems able to provide useful data for presurgical localization of critical cortical areas. Integration of morphostructural information provided by computed tomography and magnetic resonance imaging, with functional characterization and cyto-histologic evaluation of biologic markers, may assist in answering the open diagnostic questions concerning brain tumors.

Evaluation of human transferrin radiolabeled with N-succinimidyl 4-[fluorine-18](fluoromethyl) benzoate.

UNLABELLED: Iron metabolism plays a key role in cell proliferation and survival in rapidly growing cancer cells. Uptake is mediated by the carrier protein transferrin. The increased need for iron has been used as a method to target tumors and there is well-documented evidence that certain tumors can be imaged with tracers such as 67Ga, that mimic transferrin-mediated iron uptake. To obtain a tracer that would be better able to quantitate transferrin kinetics and indirectly evaluate iron metabolism, we have labeled human transferrin with the positron emitter, 18F, with a one-step high-specific activity method developed in our laboratory. METHODS: We measured the binding affinities of [18F]diferric (holo-) and iron-free (apo-) transferrin on two human cell lines. We also compared cellular uptake of [18F]holo-transferrin and [67Ga]citrate in various conditions, and washout of label incorporated into cells. RESULTS: The binding affinity of [18F]holo-transferrin was found to be the same as that reported for [125I]holo-transferrin. In our hands there was no significant difference in binding affinity between diferric holo-transferrin and iron-free apo-transferrin. [18F]holo-transferrin uptake rapidly reaches a steady-state equilibrium between the intracellular and extracellular environment, while gallium accumulation linearly increases with time. [18F]holo-transferrin is rapidly recycled out of the cell with similar kinetics to those reported for [125I]holo-transferrin. CONCLUSION: [18F]holo-transferrin displays the properties of native transferrin and appears suitable for quantitative evaluation of transferrin kinetics in vivo.

Preliminary results for positron emission mammography: real-time functional breast imaging in a conventional mammography gantry.

In order to optimally integrate radiotracer breast imaging within the breast clinic, anatomy and pathology should be easily correlated with functional nuclear medicine breast images. As a first step in the development of a hybrid functional/anatomic breast imaging platform with biopsy capability, a conventional X-ray mammography gantry was modified to image the compressed breast with positron emitters. Phantom studies with the positron emission mammography (PEM) device showed that a 1-cc hot spot could be detected within 5 min. A preliminary clinical trial demonstrated in vivo visualization of primary breast cancer within 4 min. For sites where positron-emitting radionuclides are available, PEM promises to achieve low-cost directed functional examination of breast abnormalities, with the potential for achieving X-ray correlation and image-guided biopsy.

Decreased cerebral glucose metabolism in patients with brain tumors: an effect of corticosteroids.

The authors measured cerebral glucose metabolism (CMRglu) using [18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in patients with brain tumors to evaluate the effect of exogenous corticosteroids (in this instance, dexamethasone) on glucose metabolism. Fifty-six FDG-PET studies obtained in 45 patients with unilateral supratentorial brain tumors were analyzed. Patients with brain tumors were divided into three groups: 1) patients with cushingoid symptoms, who had been treated with combinations of radiotherapy and chemotherapy taking oral dexamethasone; 2) patients not taking dexamethasone but treated with radiotherapy; and 3) patients not taking dexamethasone who had not been treated with radiotherapy. Serial FDG-PET scans were obtained in eight of the cushingoid patients. Glucose metabolism was measured in the contralateral cerebral and ipsilateral cerebellar hemispheres in patients and compared to measurements taken from 19 normal volunteers. The authors found that in the cushingoid brain tumor patients there was a marked reduction in CMRglu compared to normal volunteers and other brain tumor patients (Kruskal-Wallis test; p 0.001). In the majority of patients who had serial FDG-PET scans, there was a decline in glucose metabolism over time and in one patient, in whom dexamethasone was reduced in dosage, there was a subsequent increase in CMRglu. The authors conclude that there is a generalized reduction in CMRglu in brain tumor patients taking dexamethasone compared to other brain tumor patients and normal volunteers, and that this effect is independent of radiotherapy, concurrent anticonvulsant medication, and transhemispheric functional disconnection (transhemispheric diaschisis).