Breast Cancer Imaging with Novel PET Tracers.

Whereas (18)F-fluorodeoxyglucose (FDG)-PET/computed tomography has proven to be valuable for breast cancer diagnosis and response evaluation, it is likely that PET radiopharmaceuticals beyond FDG will contribute further to the understanding of breast cancer and thereby further direct breast cancer care. Increasingly specific and quantitative approaches will help direct treatment selection from an ever-expanding and increasing array of targeted breast cancer therapies. This article highlights 4 areas of ongoing research where preliminary patient results look promising: (1) tumor perfusion and angiogenesis, (2) drug delivery and transport, (3) tumor receptor imaging, and (4) early response evaluation. For each area, the biologic background is reviewed and early results are highlighted.

Steady-state free precession MRA of the renal arteries: breath-hold and navigator-gated techniques vs. CE-MRA.

PURPOSE: To explore the use of breath-hold and navigator-gated noncontrast Steady State Free Precession (SSFP) MR angiography (MRA) protocols for the evaluation of renal artery stenosis (RAS). MATERIALS AND METHODS: Twenty patients referred to rule out RAS were imaged using two breath-hold and one navigator-gated SSFP MRA sequences. All patients underwent contrast-enhanced MRA (CE-MRA). Two radiologists evaluated all sequences both qualitatively (blur, artifacts, reader confidence) and quantitatively (maximum stenosis). Using CE-MRA as truth, a receiver operating characteristics (ROC) curve was generated and a statistical analysis of navigator-gated SSFP (Nav SSFP) was performed. RESULTS: Seven patients had >50% renal artery stenosis by CE-MRA. Nav SSFP performed significantly better than either breath-hold SSFP technique in terms of blur, artifacts, and reader confidence. Using a 50% threshold for stenosis, sensitivity for detecting RAS was 100%, with a specificity of 85% and a negative predictive value of 100%. The average mean stenosis difference between Nav SSFP and CE-MRA was 9 +/- 9%. CONCLUSION: Nav SSFP outperformed breath-hold SSFP in measures of image quality and reader confidence. Sensitivity and negative predictive value for detecting RAS with Nav SSFP was perfect, with an acceptable specificity of 85%. This suggests further study is warranted to evaluate Nav SSFP as a noncontrast screening technique for renal artery stenosis.

Diagnosis of recurrent and metastatic disease using f-18 fluorodeoxyglucose-positron emission tomography in breast cancer.

One of the major strengths of F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) in breast cancer imaging is in the evaluation of patients who have suspected loco-regional recurrence or distant metastasis. In general, FDG-PET is more sensitive than conventional imaging for the detection of recurrent disease. Because of its ability to more accurately stage patients who have advanced breast cancer, FDG-PET has a significant impact on choice of treatment and management in this patient group.

Navigator-gated MR angiography of the renal arteries: a potential screening tool for renal artery stenosis.

OBJECTIVE: The purpose of our study was to determine how well unenhanced navigator-gated steady-state free precession (Nav SSFP) MR angiography (MRA) performs as a screening test for the detection of renal artery stenosis. SUBJECTS AND METHODS: Forty patients referred to rule out renal artery stenosis were imaged using an optimized Nav SSFP MRA sequence before conventional contrast-enhanced MRA (CE-MRA). Two radiologists evaluated Nav SSFP for maximum stenosis measurement, and comparison was made with CE-MRA results. RESULTS: Fifteen of the 40 patients had greater than 50% renal artery stenosis as determined on CE-MRA. Sensitivity for detecting renal artery stenosis with Nav SSFP was 100%; specificity, 84%; negative predictive value, 100%; and positive predictive value, 79%. The average mean stenosis difference between Nav SSFP and CE-MRA was 10% +/- 9%. CONCLUSION: Sensitivity and negative predictive value for the detection of renal artery stenosis using Nav SSFP were perfect, with an acceptable specificity of 84%. This suggests Nav SSFP is a promising technique for simple unenhanced screening for the detection of renal artery stenosis.

FDG PET, PET/CT, and breast cancer imaging.

Currently, the clinical role of positron emission tomography (PET) and PET/computed tomography (CT) in patients with breast cancer is to provide additional information in select scenarios in which results of conventional imaging are indeterminate or of limited utility. There is currently no clinical role for fluorodeoxyglucose (FDG) PET in detection of breast cancer or evaluation of axillary lymph nodes, but these are areas of active research. FDG PET is complementary to conventional staging procedures and should not be a replacement for either bone scintigraphy or diagnostic CT. FDG PET and PET/CT have been shown to be particularly useful in the restaging of breast cancer, in evaluation of response to therapy, and as a problem-solving method when results of conventional imaging are equivocal. In these situations, FDG PET often demonstrates locoregional or unsuspected distant disease that affects management. PET has demonstrated a particular capability for evaluation of chemotherapy response in both patients with locally advanced breast carcinoma and those with metastatic disease.

Current and future use of positron emission tomography (PET) in breast cancer.

Positron emission tomography (PET) is a radiotracer imaging method that is increasingly used in both the clinical care of breast cancer patients and in translational breast cancer research. This review emphasizes current and future clinical applications of PET to breast cancer, and highlights some translational research using PET to elucidate the clinical biology of breast cancer. PET principles are reviewed, followed by a review of current applications of (18)F-fluorodeoxyglucose (FDG) to clinical breast cancer care. Finally we review work done with other radiopharmaceuticals beyond FDG designed to image a number of aspects of breast cancer biology, emphasizing those most likely to enter clinical trials in the near future.

Utilizing SENSE to reduce scan duration in high-resolution contrast-enhanced renal MR angiography.

PURPOSE: To evaluate the use of sensitivity encoding (SENSE) to reduce scan time and decrease detrimental artifacts arising from motion and bolus profile effects during contrast-enhanced MR angiography (CE-MRA) of the renal arteries (RAs). MATERIALS AND METHODS: A direct comparison of conventional and SENSE (acceleration factor 2) CE-MRA protocols was performed on 20 patients. Each patient underwent both scans. Both protocols achieved the same resolution, but the SENSE protocol was 50% faster and utilized a faster injection than the conventional scan. Three radiologists graded the images for image quality, artifact levels, and reader confidence. RESULTS: While the signal-to-noise ratio (SNR) decreased (26+/-5 vs. 30+/-10; P=0.04) with the SENSE protocol, the image-quality scores for four identified segments of the RAs increased or were unchanged. The largest improvements in image quality occurred in the more distal segments of the RAs. Parenchymal ringing (P=0.005) and RA blurring (P=0.006) were significantly reduced, and there was a trend toward improvement of RA ringing despite the increased injection rate. CONCLUSION: The faster SENSE scan maintained nearly the same SNR (due to faster injection of Gd-chelate), reduced artifact levels, and improved image quality ratings for the distal renal vessels.

Diagnosis of Recurrent and Metastatic Disease Using F-18 Fluorodeoxyglucose-Positron Emission Tomography.

One of the major strengths of F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) in breast cancer imaging is in the evaluation of patients who have suspected loco-regional recurrence or distant metastasis. In general, FDG-PET is more sensitive than conventional imaging for the detection of recurrent disease. Because of its ability to more accurately stage patients who have advanced breast cancer, FDG-PET has a significant impact on choice of treatment and management in this patient group.

Evolving role of positron emission tomography in breast cancer imaging.

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used for detection, staging, and response monitoring in breast cancer patients. Although studies have proven its accuracy in detection of the primary tumor and axillary staging, its most important current clinical application is in detection and defining the extent of recurrent or metastatic breast cancer and for monitoring response to therapy. PET is complementary to conventional methods of staging in that it provides better sensitivity in detecting nodal and lytic bone metastases; however, it should not be considered a substitute for conventional staging studies, including computed tomography and bone scintigraphy. FDG uptake in the primary tumor carries prognostic information, but the underlying biochemical mechanisms responsible for enhanced glucose metabolism have not been completely elucidated. Future work using other PET tracers besides FDG will undoubtedly help our understanding of tumor biology and help tailor therapy to individual patient by improving our ability to quantify the therapeutic target, identify drug resistance factors, and measure and predict early response.

Evaluation of the internal mammary lymph nodes by FDG-PET in locally advanced breast cancer (LABC).

The presence of internal mammary (IM) lymph node metastases in breast cancer predicts outcome and may alter treatment. Standard imaging has limited usefulness for evaluation of the IM chain because of low sensitivity. Our preliminary studies suggested that [F-18]-2-fluoro-d-glucose positron emission tomography (FDG-PET) improves the detection of IM and mediastinal metastases. We therefore performed a retrospective review of women who underwent FDG-PET prior to treatment to determine the benefit of PET for imaging IM disease. The records of 28 consecutive patients undergoing FDG-PET prior to neoadjuvant chemotherapy for suspected locally advanced breast cancer (LABC) were reviewed. The presence of abnormal IM uptake on FDG-PET was noted. IM uptake on FDG PET was compared with standard radiographic imaging and was correlated with putative risk factors for IM involvement and with clinical patterns of failure. Patients did not undergo IM biopsy; however, patterns of failure were assessed to validate the FDG-PET findings. Clearly abnormal FDG uptake in the IM nodes was seen in 7 of 28 women (25%). Prospective conventional chest imaging failed to identify IM metastases in any patient. IM uptake on PET was associated with large size of the primary tumor (P = 0.03) and with inflammatory disease (P = 0.04). The presence of IM FDG uptake predicted failure by a pattern consistent with spread from IM lymph node metastasis. FDG-PET appears to be a useful noninvasive modality to detect IM metastases in LABC. Pathologic verification in a prospective study is necessary to confirm these findings.

Impact of FDG PET on defining the extent of disease and on the treatment of patients with recurrent or metastatic breast cancer.

OBJECTIVE: Our aim was to evaluate the impact of FDG PET on defining the extent of disease and on the treatment of patients with advanced breast cancer. MATERIALS AND METHODS: The medical records of 125 consecutive patients with recurrent or metastatic breast cancer referred for FDG PET from January 1998 through May 2002 were retrospectively reviewed. The rationale for FDG PET referral and the impact of FDG PET on subsequent treatment decisions for patients were determined by chart review. The impact of FDG PET on defining the extent of disease was determined by comparing the FDG PET interpretation at the time of the examination with findings from conventional imaging (CI) performed before FDG PET. FDG PET results were confirmed in nearly half (n = 61) of the patients by histopathology (n = 23) or follow-up imaging (n = 38; mean follow-up interval, 21.3 months). RESULTS: Patients were referred for FDG PET for the following reasons: evaluation of disease response or viability after therapy (n = 43 [35%]), local recurrence, with intent of aggressive local treatment (n = 39 [31%]), equivocal findings on CI (n = 25 [20%]), evaluation of disease extent in patients with known metastases (n = 13 [10%]), and elevated tumor markers with unknown disease site (n = 5 [4%]). Compared with CI findings, the extent of disease increased in 54 (43%), did not change in 41 (33%), and decreased in 30 (24%) of 125 patients using FDG PET. Results of FDG PET altered the therapeutic plan in 40 (32%), directly helped to support the therapeutic plan in 34 (27%), and did not change the plan devised before FDG PET in 51 (41%) of 125 patients. FDG PET altered therapy most frequently in the patients suspected of having locoregional recurrence and in those being evaluated for treatment response versus other referral categories (p = 0.04). For patients with confirmation of FDG PET findings, the sensitivity, specificity, and accuracy of FDG PET were 94%, 91%, and 92%, respectively. CONCLUSION: FDG PET contributes significantly to defining the extent of disease and deciding on treatment of patients with advanced breast cancer.

Current and future uses of positron emission tomography in breast cancer imaging.

Positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) has been used for the detection, staging, and response monitoring in breast cancer patients. Although studies have proven its accuracy in detection of the primary tumor and axillary staging, its most important current clinical application is in detection and defining the extent of recurrent or metastatic breast cancer and for monitoring response to therapy. PET is complementary to conventional methods of staging in that it provides better sensitivity in detecting nodal and lytic bone metastases; however, it should not be considered a substitute for conventional staging studies, including computed tomography and bone scintigraphy. FDG uptake in the primary tumor carries prognostic information, but the underlying biochemical mechanisms that are responsible for enhanced glucose metabolism have not been completely elucidated. Future work using other PET tracers besides FDG will undoubtedly help our understanding of tumor biology, improve our ability to measure and predict response and help tailor therapy to individual patients.

Preoperative evaluation of patients awaiting liver transplantation: comparison of multiphasic contrast-enhanced 3D magnetic resonance to helical computed tomography examinations.

PURPOSE: To determine the feasibility of using a multiphasic magnetic resonance (MR) examination to evaluate the hepatic arterial anatomy and parenchyma in patients awaiting orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Twenty consecutive patients awaiting OLT underwent multiphasic MR (using a T1-weighted 3D gadolinium-enhanced gradient-echo (GRE) sequence and two separate injections of contrast material) and computed tomography (CT) imaging; both imaging studies were performed within a 1-week period for each patient. Quantitative and qualitative assessment of the hepatic arterial system on MR data was performed. Two independent observers classified the hepatic arterial anatomy and evaluated the hepatic parenchyma from the MR data. The prospective CT interpretation was used as the gold standard. RESULTS: Overall qualitative rating of hepatic arterial system-to-background contrast on MR data was good to excellent (average pooled score of 2.00 +/- 0.27), with no significant difference between the two observers after the first or second injections of contrast material. Classification of hepatic arterial anatomy by MR angiography (MRA) and CT angiography (CTA) was concordant in 85% (17/20) of patients and discordant in 15% (3/20) of patients. Focal parenchymal lesions were detected in 25% (5/20) of patients by MR and CT; however, two lesions in one patient with multiple lesions were detected only with MR. CONCLUSION: Multiphasic T1-weighted 3D gadolinium-enhanced MR examination can provide comprehensive evaluation of the hepatic arterial anatomy and parenchyma in patients awaiting OLT. MR may offer an advantage over CT in the detection of focal parenchymal lesions.

Utilizing SENSE to achieve lower station sub-millimeter isotropic resolution and minimal venous enhancement in peripheral MR angiography.

PURPOSE: To use the parallel imaging technique, sensitivity encoding (SENSE), to increase spatial resolution and decrease venous contamination in peripheral magnetic resonance angiography (MRA). MATERIALS AND METHODS: Moving table, single-bolus peripheral contrast-enhanced (CE) -MRA was performed on nine patients. Manual table movement combined with SENSE in the upper station allowed for more rapid overall scan coverage such that acquisition of the lower station began 34 seconds after aortic contrast arrival. True sub- millimeter isotropic resolution was achieved in the lower station. RESULTS: Diagnostic MR angiograms of all three stations were obtained in all nine patients. Venous enhancement did not confound interpretation in any case. Sub-millimeter lower station resolution provided excellent vascular detail. CONCLUSION: Decreased delay time between upper and lower station acquisition in single bolus peripheral MR angiograms, now possible using parallel imaging techniques, combined with lower station sub-millimeter resolution may decrease venous contamination and increase overall interpretability, thus increasing clinical acceptance of peripheral MRA.

Detection of locoregional and distant recurrences in breast cancer patients by using FDG PET.

Cases of recurrence of breast cancer can pose considerable diagnostic and therapeutic challenges for the oncologic team. The prognosis and management decisions are based on knowledge of the true extent of disease. Conventional staging methods, including physical examination, assessment of levels of tumor markers, cross-sectional imaging, and bone scintigraphy, may not reliably demonstrate the extent of disease in all cases. Physical examination and cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging) can be problematic because (a) the sequelae of previous surgery and radiation therapy can be difficult to distinguish from recurrent neoplasms and (b) early metastatic disease (small lesions) can be difficult to distinguish from benign lesions that are too small to characterize. Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) can help clarify inconclusive findings from physical examination and cross-sectional imaging. FDG PET is more sensitive than CT in detection of lymphatic spread of disease to locoregional and mediastinal nodes. Metastases at distant sites including the lung, bone, and the liver are also readily detected at FDG PET. FDG PET has been proved accurate in restaging cases of recurrent breast cancer and will likely aid in directing therapy in these cases.