Searching for alternatives to full kinetic analysis in 18F-FDG PET: an extension of the simplified kinetic analysis method.

UNLABELLED: The most accurate way to estimate the glucose metabolic rate (or its influx constant) from (18)F-FDG PET is to perform a full kinetic analysis (or its simplified Patlak version), requiring dynamic imaging and the knowledge of arterial activity as a function of time. To avoid invasive arterial blood sampling, a simplified kinetic analysis (SKA) has been proposed, based on blood curves measured from a control group. Here, we extend the SKA by allowing for a greater variety of arterial input function (A(t)) curves among patients than in the original SKA and by accounting for unmetabolized (18)F-FDG in the tumor. METHODS: Ten A(t)s measured in patients were analyzed using a principal-component analysis to derive 2 principal components describing most of the variability of the A(t). The mean distribution volume of (18)F-FDG in tumors for these patients was used to estimate the corresponding quantity in other patients. In subsequent patient studies, the A(t) was described as a linear combination of the 2 principal components, for which the 2 scaling factors were obtained from an early and a late venous sample drawn for the patient. The original and extended SKA (ESKA) were assessed using fifty-seven (18)F-FDG PET scans with various tumor types and locations and using different injection and acquisition protocols, with the K(i) derived from Patlak analysis as a reference. RESULTS: ESKA improved the accuracy or precision of the input function (area under the blood curve) for all protocols examined. The mean errors (±SD) in K(i) estimates were -12% ± 33% for SKA and -7% ± 22% for ESKA for a 20-s injection protocol with a 55-min postinjection PET scan, 20% ± 42% for SKA and 1% ± 29% for ESKA (P < 0.05) for a 120-s injection protocol with a 55-min postinjection PET scan, and -37% ± 19% for SKA and -4% ± 6% for ESKA (P < 0.05) for a 20-s injection protocol with a 120-min postinjection PET scan. Changes in K(i) between the 2 PET scans in the same patients also tended to be estimated more accurately and more precisely with ESKA than with SKA. CONCLUSION: ESKA, compared with SKA, significantly improved the accuracy and precision of K(i) estimates in (18)F-FDG PET. ESKA is more robust than SKA with respect to various injection and acquisition protocols.

Can positron emission tomography (PET) or PET/Computed Tomography (CT) acquired in a nontreatment position be accurately registered to a head-and-neck radiotherapy planning CT?

PURPOSE: To quantify the uncertainties associated with incorporating diagnostic positron emission tomography/CT (PET/CT) and PET into the radiotherapy treatment-planning process using different image registration tools, including automated and manual rigid body registration methods, as well as deformable image registration. METHODS AND MATERIALS: The PET/CTs and treatment-planning CTs from 12 patients were used to evaluate image registration accuracy. The PET/CTs also were used without the contemporaneously acquired CTs to evaluate the registration accuracy of stand-alone PET. Registration accuracy for relevant normal structures was quantified using an overlap index and differences in the center of mass (COM) positions. For tumor volumes, the registration accuracy was measured using COM positions only. RESULTS: Registration accuracy was better with PET/CT than with PET alone. The COM displacements ranged from 3.2 +/- 0.6 mm (mean +/- 95% confidence interval, for brain) to 8.4 +/- 2.6 mm (spinal cord) for registration with PET/CT data, compared with 4.8 +/- 1.7 mm (brain) and 9.9 +/- 3.1 mm (spinal cord) with PET alone. Deformable registration improved accuracy, with minimum and maximum errors of 1.1 +/- 0.8 mm (brain) and 5.4 +/- 1.4 mm (mandible), respectively. CONCLUSIONS: It is possible to incorporate PET and/or PET/CT acquired in diagnostic positions into the treatment-planning process through the use of advanced image registration algorithms, but precautions must be taken, particularly when delineating tumor volumes in the neck. Acquisition of PET/CT in the treatment-planning position would be the ideal method to minimize registration errors.

Glucose and insulin variations in patients during the time course of a FDG-PET study and implications for the "glucose-corrected" SUV.

INTRODUCTION: 2-Deoxy-2[(18)F]fluoro-d-glucose (FDG) positron emission tomography (PET) has an established role in the evaluation of cancer. Generally, tumor uptake and response to treatment are evaluated using the standardized uptake value (SUV). Some authors have proposed correcting SUV for glucose levels. Insulin is also thought to influence tumor uptake by changing uptake in other tissues. However, little attention has been paid to understanding the variability of glucose or insulin during a single PET study. METHOD: We studied the biological and instrumental variability of glucose and insulin measurements in 71 nondiabetic patients undergoing FDG-PET studies. Multiple glucose measurements were obtained in all 71 subjects, and in 69 of these 71 subjects, multiple serum insulin measurements were made. We determined the coefficient of observed variation (CV(ow)) and the coefficient of variation attributable to biological variability (CV(bv)) for both glucose and insulin. RESULTS: The mean glucose concentration was 78.9+/-13.5 mg/dl. The mean insulin value was 6.49+/-5.92 microU/ml. The weighted mean CV(ow) and CV(bv) was 5.0% and 3.6%, respectively, for glucose and 14.2% and 8.3%, respectively, for insulin. CONCLUSIONS: Variations in the range of 3.6% are observed in glucose measurements during the time course of an FDG scan even after accounting for analytical error; larger variations of 8.3% are observed in insulin levels. Therefore, corrections of SUV for blood glucose, especially if obtained from single measurements, can introduce additional errors of at least this much.

Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction.

AIMS: In a blinded, placebo-controlled study, we investigated whether intracoronary infusion of autologous mononuclear cells from granulocyte colony-stimulating factor (G-CSF)-mobilized apheresis product or bone marrow (BM) improved sensitive outcome measures in a swine model of large myocardial infarction (MI). METHODS AND RESULTS: Four days after left anterior descending (LAD) occlusion and reperfusion, cells from BM or apheresis product of saline- (placebo) or G-CSF-injected animals were infused into the LAD. Large infarcts were created: baseline ejection fraction (EF) by magnetic resonance imaging (MRI) of 35.3 +/- 8.5%, no difference between the placebo, G-CSF, and BM groups (P = 0.16 by ANOVA). At 6 weeks, EF fell to a similar degree in the placebo, G-CSF, and BM groups (-7.9 +/- 6.0, -8.5 +/- 8.8, and -10.9 +/- 7.6%, P = 0.78 by ANOVA). Left ventricular volumes and infarct size by MRI deteriorated similarly in all three groups. Quantitative positron emission tomography (PET) demonstrated significant decline in fluorodeoxyglucose uptake rate in the LAD territory at follow-up, with no histological, angiographic, or PET perfusion evidence of functional neovascularization. Immunofluorescence failed to demonstrate transdifferentiation of infused cells. CONCLUSION: Intracoronary infusion of mononuclear cells from either BM or G-CSF-mobilized apheresis product may not improve or limit deterioration in systolic function, adverse ventricular remodelling, infarct size, or perfusion in a swine model of large MI.

Correcting tumour SUV for enhanced bone marrow uptake: retrospective 18F-FDG PET/CT studies.

PURPOSE: The concentration of F-FDG in the bone marrow is usually low. One common cause of high uptake is due to bone marrow stimulating drugs administered in conjunction with chemotherapy or radiation therapy. It has been hypothesized that the sequestration of F-FDG to the bone marrow may reduce the standardized uptake value (SUV) of a tumour. We tested this hypothesis by quantifying total F-FDG uptake in the bone marrow of patients with visibly enhanced bone marrow uptake and computing its effect on tumour SUV. METHODS: Total F-FDG in bone marrow was measured in two groups of PET/CT studies: one (n=19) with visibly enhanced bone marrow, the other (n=5), a baseline group with 'normal' levels of uptake. To measure the F-FDG in bone marrow, the entire skeleton in the CT was segmented from surrounding tissue, and the resulting volume applied to the PET image. Using kinetic analysis we show that the predicted correction factor to tumour SUV is given by (1-q0/Q)/(1-q/Q), where Q is the injected dose, and q and q0 are enhanced and baseline bone marrow uptake (MBq). RESULTS: The enhanced bone marrow uptake averaged 8.9+/-3.2% of injected dose (15.2% max) vs. 4.2+/-0.4% (4.6% max) at baseline. This resulted in a predicted artificial decrease in tumour SUV of up to 11.5% (4.9+/-4.3%, on average). CONCLUSION: Enhanced bone marrow uptake is predicted to reduce tumour SUVs by as much as 11.5% in our patient group and is a potential confounding factor in using SUV for monitoring tumour response to therapy.

Partial-volume effect in PET tumor imaging.

PET has the invaluable advantage of being intrinsically quantitative, enabling accurate measurements of tracer concentrations in vivo. In PET tumor imaging, indices characterizing tumor uptake, such as standardized uptake values, are becoming increasingly important, especially in the context of monitoring the response to therapy. However, when tracer uptake in small tumors is measured, large biases can be introduced by the partial-volume effect (PVE). The purposes of this article are to explain what PVE is and to describe its consequences in PET tumor imaging. The parameters on which PVE depends are reviewed. Actions that can be taken to reduce the errors attributable to PVE are described. Various PVE correction schemes are presented, and their applicability to PET tumor imaging is discussed.

Partial-volume correction in PET: validation of an iterative postreconstruction method with phantom and patient data.

UNLABELLED: Partial-volume errors (PVEs) in PET can cause incorrect estimation of radiopharmaceutical uptake in small tumors. An iterative postreconstruction method was evaluated that corrects for PVEs without a priori knowledge of tumor size or background. METHODS: Volumes of interest (VOIs) were drawn on uncorrected PET images. PVE-corrected images were produced using an iterative 3-dimensional deconvolution algorithm and a local point spread function. The VOIs were projected on the corrected image to estimate the PVE-corrected mean activity concentration. These corrected mean values were compared with uncorrected maximum and mean values. Simulated data were generated as a first test of the correction algorithm. Phantom measurements were made using (18)F-FDG-filled spheres in a scattering medium. Clinical validation used 154 surrogate tumors from 9 patients. The surrogate tumors were blood-pool images of the descending aorta as well as mesenteric and iliac arteries and veins. Surrogate tumors ranged in diameter from 5 to 25 mm. Analysis used (18)F-FDG and (11)C-CO datasets (both dynamic and static). Values representing "truth" were derived from imaging the blood pool in large structures (e.g., the left ventricle, left atrium, or sections of the aorta) where PVEs were negligible. Surrogate tumor sizes were measured from contrast CT. RESULTS: The PVE-correction technique, when applied to the mean value in spheric phantoms, yielded recovery coefficients of 87% for an 8-mm-diameter sphere and between 100% and 103% for spheres between 13 and 29 mm. For the human studies, PVE-corrected data recovered a large fraction of the true activity concentration (86% +/- 7% for an 8-mm-diameter tumor and 98% +/- 8% for tumors between 10 and 24 mm). For tumors smaller than 18 mm, the PVE-corrected mean values were less biased (P<0.05) than the uncorrected maximum or mean values. CONCLUSION: Iterative postreconstruction PVE correction generated more accurate uptake measurements in subcentimeter tumors for both phantoms and patients than the uncorrected values. The method eliminates the requirement for segmenting anatomic data and estimating tumor metabolic size or tumor background level. This technique applies a PVE correction to the mean voxel value within a VOI, yielding a more accurate estimate of uptake than the maximum voxel value.

The influence of tumor oxygenation on hypoxia imaging in murine squamous cell carcinoma using [64Cu]Cu-ATSM or [18F]Fluoromisonidazole positron emission tomography.

[64Cu]Cu(II)-ATSM (64Cu-ATSM) and [18F]-Fluoromisonidazole (18F-FMiso) tumor binding as assessed by positron emisson topography (PET) was used to determine the responsiveness of each probe to modulation in tumor oxygenation levels in the SCCVII tumor model. Animals bearing the SCCVII tumor were injected with 64Cu-ATSM or 18F-FMiso followed by dynamic small animal PET imaging. Animals were imaged with both agents using different inspired oxygen mixtures (air, 10% oxygen, carbogen) which modulated tumor hypoxia as independently assessed by the hypoxia marker pimonidazole. The extent of hypoxia in the SCCVII tumor as monitored by the pimonidazole hypoxia marker was found to be in the following order: 10% oxygen>air>carbogen. Tumor uptake of 64Cu-ATSM could not be changed if the tumor was oxygenated using carbogen inhalation 90 min post-injection suggesting irreversible cellular uptake of the 64Cu-ATSM complex. A small but significant paradoxical increase in 64Cu-ATSM tumor uptake was observed for animals breathing air or carbogen compared to 10% oxygen. There was a positive trend toward 18F-FMiso tumor uptake as a function of changing hypoxia levels in agreement with the pimonidazole data. 64Cu-ATSM tumor uptake was unable to predictably detect changes in varying amounts of hypoxia when oxygenation levels in SCCVII tumors were modulated. 18F-FMiso tumor uptake was more responsive to changing levels of hypoxia. While the mechanism of nitroimidazole binding to hypoxic cells has been extensively studied, the avid binding of Cu-ATSM to tumors may involve other mechanisms independent of hypoxia that warrant further study.

The influence of tumor oxygenation on (18)F-FDG (fluorine-18 deoxyglucose) uptake: a mouse study using positron emission tomography (PET).

BACKGROUND: This study investigated whether changing a tumor's oxygenation would alter tumor metabolism, and thus uptake of (18)F-FDG (fluorine-18 deoxyglucose), a marker for glucose metabolism using positron emission tomography (PET). RESULTS: Tumor-bearing mice (squamous cell carcinoma) maintained at 37 degrees C were studied while breathing either normal air or carbogen (95% O(2), 5% CO2), known to significantly oxygenate tumors. Tumor activity was measured within an automatically determined volume of interest (VOI). Activity was corrected for the arterial input function as estimated from image and blood-derived data. Tumor FDG uptake was initially evaluated for tumor-bearing animals breathing only air (2 animals) or only carbogen (2 animals). Subsequently, 5 animals were studied using two sequential (18)F-FDG injections administered to the same tumor-bearing mouse, 60 min apart; the first injection on one gas (air or carbogen) and the second on the other gas. When examining the entire tumor VOI, there was no significant difference of (18)F-FDG uptake between mice breathing either air or carbogen (i.e. air/carbogen ratio near unity). However, when only the highest (18)F-FDG uptake regions of the tumor were considered (small VOIs), there was a modest (21%), but significant increase in the air/carbogen ratio suggesting that in these potentially most hypoxic regions of the tumor, (18)F-FDG uptake and hence glucose metabolism, may be reduced by increasing tumor oxygenation. CONCLUSION: Tumor (18)F-FDG uptake may be reduced by increases in tumor oxygenation and thus may provide a means to further enhance (18)F-FDG functional imaging.

Fluorodeoxyglucose positron emission tomography (FDG-PET) for monitoring lymphadenopathy in the autoimmune lymphoproliferative syndrome (ALPS).

Autoimmune lymphoproliferative syndrome (ALPS) is associated with mutations that impair the activity of lymphocyte apoptosis proteins, leading to chronic lymphadenopathy, hepatosplenomegaly, autoimmunity, and an increased risk of lymphoma. We investigated the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in discriminating benign from malignant lymphadenopathy in ALPS. We report that FDG avidity of benign lymph nodes in ALPS can be high and, hence, by itself does not imply presence of lymphoma; but FDG-PET can help guide the decision for selecting which of many enlarged nodes in ALPS patients to biopsy when lymphoma is suspected.

Imaging approaches for monitoring chemotherapy.

Positron emission tomography (PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are two, often complementary, imaging modalities of great potential use for monitoring tumor therapy. They permit physiologic measures such as metabolism, perfusion, small vessel permeability and others to be made. Such measures might prove valuable supplements to the usual morphologic measures now commonly used. We give here an overview of some of the salient features of both methodologies for making such physiologic measurements.:

Simplified kinetic analysis of tumor 18F-FDG uptake: a dynamic approach.

UNLABELLED: Standardized uptake value (SUV) is often used to quantify (18)F-FDG tumor use. Although useful, SUV suffers from known quantitative inaccuracies. Simplified kinetic analysis (SKA) methods have been proposed to overcome the shortcomings of SUV. Most SKA methods rely on a single time point (SKA-S), not on tumor uptake rate. We describe a hybrid between Patlak analysis and existing SKA-S methods, using multiple time points (SKA-M) but reduced imaging time and without measurement of an input function. We compared SKA-M with a published SKA-S method and with Patlak analysis. METHODS: Twenty-seven dynamic (18)F-FDG scans were performed on 11 cancer patients. A population-based (18)F-FDG input function was generated from an independent patient population. SKA-M was calculated using this population input function and either a short, late, dynamic acquisition over the tumor (starting 25-35 min after injection and ending approximately 55 min after injection) or dynamic imaging 10 or 25 min to approximately 55 min after injection but using only every second or third time point, to permit a 2- or 3-field-of-view study. SKA-S was also calculated. Both SKA-M and SKA-S were compared with the gold standard, Patlak analysis. RESULTS: Both SKA-M (1 field of view) and SKA-S correlated well with Patlak slope (r > 0.99, P < 0.001, and r = 0.96, P < 0.001, respectively), as did multilevel SKA-M (r > 0.99 and P < 0.001 for both). Mean values of SKA-M (25-min start time) and SKA-S were statistically different from Patlak analysis (P < 0.001 and P < 0.04, respectively). One-level SKA-M differed from the Patlak influx constant by only -1.0% +/- 1.4%, whereas SKA-S differed by 15.1% +/- 3.9%. With 1-level SKA-M, only 2 of 27 studies differed from K(i) by more than 20%, whereas with SKA-S, 10 of 27 studies differed by more than 20% from K(i). CONCLUSION: Both SKA-M and SKA-S compared well with Patlak analysis. SKA-M (1 or multiple levels) had lower variability and bias than did SKA-S, compared with Patlak analysis. SKA-M may be preferred over SUV or SKA-S when a large unmetabolized (18)F-FDG fraction is expected and 1-3 fields of view are sufficient.

Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor.

PURPOSE: To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained. RESULTS: The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor. CONCLUSION: Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients.

Using positron emission tomography 2-deoxy-2-[18F]fluoro-D-glucose, 11CO, and 15O-water for monitoring androgen independent prostate cancer.

PURPOSE: Monitoring of androgen independent prostate cancer (AIPC) therapy involves monitoring prostate specific antigen (PSA) blood serum concentrations; however, the reliability of small changes in PSA values has been questioned. We performed a small pilot study to determine whether PET might be a useful monitor of changes during anti-angiogenic therapy in AIPC. PROCEDURES: Changes in tumor blood flow ([15O] water), blood volume ([11C]CO), 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake and metabolic volume were measured before and during thalidomide treatment and compared with changes in PSA in six patients with AIPC. RESULTS: The percent change in PSA correlated with the FDG Delta%SUV(mean) (r=0.94, P<0.01) and Delta%metabolic tumor volume (r=0.91, P<0.01) but less well with Delta%blood volume (r=0.65, P=0.14). Percent change blood flow values showed an inverse correlation with percent changes in PSA (r=-0.83, P=0.032). CONCLUSIONS: PET measures of tumor blood flow and metabolism may have use in monitoring the physiologic changes occurring during anti-angiogenic therapy in AIPC.

Comparison of SUV and Patlak slope for monitoring of cancer therapy using serial PET scans.

The standardized uptake value (SUV) and the slope of the Patlak plot ( K) have both been proposed as indices to monitor the progress of disease during cancer therapy. Although a good correlation has been reported between SUV and K, they are not equivalent, and may not be equally affected by metabolic changes occurring during disease progression or therapy. We wished to compare changes in tumor SUV with changes in K during serial positron emission tomography (PET) scans for monitoring therapy. Thirteen patients enrolled in a protocol to treat renal cell carcinoma metastases were studied. Serial dynamic fluorodeoxyglucose (FDG) PET scans and computed tomography (CT) and magnetic resonance (MR) scans were performed once prior to treatment, once at 36+/-2 days after the start of treatment, and (in 7/13 subjects, 16/27 lesions) a third time at 92+/-9 days after the start of treatment. This resulted in a total of 33 scans, and 70 tumor Patlak and SUV values (one value for each lesion at each time point). SUV and K were measured over one to four predefined tumors/patient at each time point. The input function was obtained from regions of interest over the heart, combined, if necessary, with late blood samples. Over all tumors and scans, SUV and K correlated well ( r=0.97, P<0.0001). However, change in SUV with treatment over all tumor scan pairs was much less well correlated with the corresponding change in K ( r=0.73, P<0.0001). The absolute difference in % change was outside the 95% confidence limits expected from previous variability studies in 6 of 43 pairs of tumor scans, and greater than 50% in 2 of 43 tumor scan pairs. In four of the six cases, the two indices predicted opposing therapeutic outcomes. Similar results were obtained for SUV normalized by body weight or body surface area and for SUVs using mean or maximum count. Changes in CT and MR tumor cross-product dimensions correlated poorly with each other ( r=0.47, P=NS), and so could not be used to determine the "correct" PET index. Absolute values of SUV and K correlated well over the patient population. However, when monitoring individual patient therapy serially, large differences in the % changes in the two indices were occasionally found, sometimes sufficient to produce opposing conclusions regarding the progression of disease.

The role of 18F-FDG-PET in the local/regional evaluation of women with breast cancer.

PURPOSE: In women with breast cancer, knowledge of the local/regional extent of the tumor is essential for staging, treatment planning, monitoring response to therapy, and follow-up. Positron emission tomography (PET) is an important imaging test which can detect tumor at multiple sites in women with breast cancer. We compared the ability of PET to provide a comprehensive view of the local/regional extent of tumor in women with stage I, II and stage III, IV breast cancer. MATERIALS AND METHODS: Forty-six women with breast cancer underwent PET using 18F-FDG. 18FDG uptake in the breast primary tumor, associated skin, axillary and internal mammary lymph nodes, and the contralateral breast was determined qualitatively, and correlated with histologic, clinical and radiographic findings. RESULTS: Twenty-four patients were premenopausal and 22 were postmenopausal, with the following distribution according to clinical stage: stage I--2 patients, stage II--16, stage III--16, stage IV--12 patients. Among stage I, II patients, the sensitivity for detection of the primary tumor was 83.3%, and for detection of axillary lymph node metastases was 42.9%. 18FDG-PET was negative for the breast skin, contralateral breast, and internal mammary lymph nodes in all stage I, II patients, in agreement with clinical and radiographic findings. Among 28 stage III, IV patients, the sensitivity of 18FDG-PET for detection of the primary tumor was 90.5%, and for detection of axillary lymph node metastases 83.3%. Fourteen patients had clinically advanced changes in the skin, and the sensitivity of PET for detection of skin changes was 76.9%. 18FDG-PET was positive in the internal mammary lymph nodes in 25.0%, and negative in the contralateral breast in all patients with stage III, IV breast cancer. 18FDG-PET was studied in 10 patients following neoadjuvant chemotherapy, and showed a strong correlation with clinical response, and with clinical and pathological findings post-treatment at multiple local/regional sites. CONCLUSION: 18FDG-PET can provide a comprehensive image of local/regional tumor in women with breast cancer. 18FDG-PET may play a greater role in women with stage III, IV breast cancer because of increased sensitivity and the increased involvement of multiple local/regional sites with tumor.