Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy.

BACKGROUND: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. 18F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes 18F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. METHODS: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with 18F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with 18F-FES 1-5 days post administration of Z-endoxifen. RESULTS: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. CONCLUSION: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

First-in-human phase 0 study of 111In-CHX-A"-DTPA trastuzumab for HER2 tumor imaging.

INTRODUCTION: Tumors over-expressing the human epithelial receptor 2 (HER2) or exhibiting amplification or mutation of its proto-oncogene have a poorer prognosis. Using trastuzumab and/or other HER2 targeted therapies can increase overall survival in patients with HER2(+) tumors making it critical to accurately identify patients who may benefit. We report on a Phase 0 study of the imaging agent, 111In-CHX-A"-DTPA trastuzumab, in patients with known HER2 status to evaluate its safety and biodistribution and to obtain preliminary data regarding its ability to provide an accurate, whole-body, non-invasive means to determine HER2 status. METHODS: 111In-CHX-A"-DTPA trastuzumab was radiolabeled on-site and slowly infused into 11 patients who underwent single (n=5) or multiple (n=6) ɣ-camera (n=6) and/or SPECT (n=8) imaging sessions. RESULTS: No safety issues were identified. Visual and semi-quantitative imaging data were concordant with tissue HER2 expression profiling in all but 1 patient. The biodistribution showed intense peak liver activity at the initial imaging timepoint (3.3h) and a single-phase clearance fit of the average time-activity curve (TAC) estimated t1/2=46.9h (R2=0.97; 95%CI 41.8 to 53h). This was followed by high gastrointestinal (GI) tract activity peaking by 52h. Linear regression predicted GI clearance by 201.2h (R2 =0.96; 95%CI 188.5 to 216.9h). Blood pool had lower activity with its maximum on the initial images. Non-linear regression fit projected a t1/2=34.2h (R2 =0.96; 95%CI 25.3 to 46.3h). Assuming linear whole-body clearance, linear regression projected complete elimination (x-intercept) at 256.5hr (R2=0.96; 95%CI 186.1 to 489.2h). CONCLUSION: 111In-CHX-A"-DTPA trastuzumab can be safely imaged in humans. The biodistribution allowed for visual and semiquantitative analysis with results concordant with tissue expression profiling in 10 of 11 patients. Advances in Knowledge and Implications for Patient Care Using readily available components and on-site radiolabeling 111In-CHX-A"-DTPA trastuzumab SPECT imaging may provide an economical, non-invasive means to detect HER2 over-expression.

"Robo-Rad": an inexpensive user-friendly multimedia report system for radiology.

BACKGROUND AND PURPOSE: The complex information obtained by CT, MR, and ultrasound examinations is often difficult to convey with a written report. Today's multimedia computer technology provides a medium within which the audio and the visual components of a radiologic consultation can be made available simultaneously, with the projected capability of remote access from any personal computer. A system was developed to run on low-end computer systems with image quality adequate for reporting purposes and prudent memory management (each report occupies < 4 MB). With this system-"Robo-Rad"-the image and radiologist are recorded simultaneously while he or she describes and points out (with a mouse) areas of interest. This dynamic report, along with patient data, can be retrieved and viewed by the consulting physician at his/her convenience using a low-end PC or Macintosh computer. MATERIALS AND METHODS: To assess the clinical utility of Robo-Rad, survey responses were solicited from clinical physicians at the Penn State University Hospital (41.5% faculty/fellows, 31.7% residents, 11.8% medical students, 2% clinical nursing; n = 101) during a hands-on demonstration using studies of 35 consecutive inpatients whose CT scans had been dictated into the system. RESULTS: In an average week, the surveyed professionals ordered 3.2 +/- 3.0 CT studies, reviewed 3.8 +/- 3.0 CTs, spent 1.5 +/- 2.0 hours locating Ct studies, and discussed 2.3 +/- 1.9 CT cases with a radiologist. The average time spent discussing a single CT case with a radiologist was reported as 9.4 +/- 5.9 minutes. On a five-point rating scale (1 = not at all to 5 = very much so), respondents indicated that the Robo-Rad report was helpful (4.3 +/- 0.7) and provided clinically important information that would be difficult to convey with current dictation systems (4.2 +/- 0.8). Desire to discuss the case with a radiologist in addition to viewing the Robo-Rad report scored 3.2 +/- 1.0. If such a system were readily available, 91.8% of the respondents indicated that they would use it in addition to the currently available written report and audio dictation system, and 96.6% would use it instead of the current system. Local area network and modems were the modalities of highest interest for remote access (69.3% and 44.6%, respectively). CONCLUSIONS: Judging by these data, the Robo-Rad system would be of benefit to clinicians. It provides a user-friendly, low-cost multimedia radiology report utilizing readily available technology to improve radiologist-clinician communication.

A nonischemic electrocardiogram does not always predict a small myocardial infarction: results with acute myocardial perfusion imaging.

BACKGROUND: A nonischemic electrocardiogram (ECG) in association with myocardial infarction (MI) indicates a small MI in some but not all cases. Myocardial perfusion imaging using technetium-99m sestamibi offers the ability to better characterize these "electrically silent" infarctions. METHODS: Patients considered low risk for myocardial infarction with a normal or nonischemic ECG (no significant ST elevation, ST depression, ischemic T-wave inversion, or left bundle branch block) underwent early emergency department perfusion imaging, followed by serial myocardial marker sampling. Risk area (defect size) was quantitated by use of a 50% threshold from multiple short-axis slices. RESULTS: A total of 87 patients with nonischemic ECGs had myocardial infarction (mean peak creatine kinase [CK] 710 +/- 720 U/L, range 111-3196 U/L). Peak CKs were lower in the 7 patients with negative perfusion imaging (420 +/- 290 U/L vs 730 +/- 740 U/L, P =.06). Mean risk area was 18% +/- 11% of the left ventricle (range 0%-62%) and was not significantly different among the different infarct-related arteries. Patients with normal ECGs had a similar risk area compared with other patients (16% +/- 12% vs 19 +/- 12%, P =.25). Coronary angiography was performed in 81 patients, with significant stenoses in 74 (91%) (37 one-vessel, 19 two-vessel, 18 three-vessel), with the infarct related artery most commonly the left circumflex (n = 32 [38%]). CONCLUSIONS: The ischemic risk area in patients with a nonischemic ECG was comparable to patients with inferior ST-elevation myocardial infarction found in previous studies. A nonischemic ECG does not predict a small ischemic risk area.

8:45-9:00. Using PET 18F-FDG, 11CO, and 15O-water for Monitoring Prostate Cancer During a Phase II Anti-angiogenic Drug Trial with Thalidomide.

Assessing prostate metastases is difficult with conventional radiographic modalities as few patients have soft tissue involvement and most have only bone lesions. Even with FDG PET, problems due to decreased avidity compared to other tumor types can occur. We assessed PET's ability to monitor changes in such tumors during an anti-angiogenic therapy. We measured changes in tumor blood flow (15O), blood volume (11CO), 18F-FDG uptake and "metabolic volume" before and during thalidomide treatment, to see if these changes correlated with changes in PSA values.Six patients with androgen-independent prostate cancer were imaged with 18F-FDG, 11CO, and 15O water before and during (mean interval 63 days, range 55-76 days) thalidomide therapy (200-1200mg/day). Lesions were visually identified on FDG images (9 bone, 5 soft tissue lesions). VOI's were generated by 3D region growing, with a 50% maximum pixel threshold. These VOI's were registered with, and applied to, the 11CO and water studies. Correlations with PSA values were done using the Spearman rank test.The change in maximum (r = 0.77, p = 0.06) and mean FDG value (r = 0.83, p = 0.03), functional FDG volume (r = 0.66, p = 0.14), and 11-CO blood volume (r = 0.77, p = 0.06) all correlated with the change in PSA. Changes in blood flow values were smaller than the variance of the method for repeated measures, likely due to low flow values in bone.Changes in blood volume measured by 11CO, and the mean and peak activity and functional volume measured by 18F-FDG, correlate with changes in PSA and may be useful in monitoring anti-angiogenic therapy in prostate cancer.