Assessment of a statistical AIF extraction method for dynamic PET studies with 15O water and 18F fluorodeoxyglucose in locally advanced breast cancer patients

Blood flow-metabolism mismatch from dynamic positron emission tomography (PET) studies with O-15-labeled water (H2O) and F-18-labeled fluorodeoxyglucose (FDG) has been shown to be a promising diagnostic for locally advanced breast cancer (LABCa) patients. The mismatch measurement involves kinetic analysis with the arterial blood time course (AIF) as an input function. We evaluate the use of a statistical method for AIF extraction (SAIF) in these studies. Fifty three LABCa patients had dynamic PET studies with H2O and FDG. For each PET study, two AIFs were recovered, an SAIF extraction and also a manual extraction based on a region of interest placed over the left ventricle (LV-ROI). Blood flow-metabolism mismatch was obtained with each AIF, and kinetic and prognostic reliability comparisons were made. Strong correlations were found between kinetic assessments produced by both AIFs. SAIF AIFs retained the full prognostic value, for pathologic response and overall survival, of LV-ROI AIFs. (c) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI

Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses

Background: 18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT. Methods: Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12). Results: No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng*h/mL to 1.339 ng*h/mL with a mean of 0.802 � 0.303 ng*h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial. Conclusion: This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously.This study was supported by NIH grant R01 CA115559, 1R01 CA107264, and 1R01 CA80907

Effect of 18F-FDG Uptake Time on Lesion Detectability in PET Imaging of Early-Stage Breast Cancer

Prior reports have suggested that delayed 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) oncology imaging can improve the contrast-to-noise ratio (CNR) for known lesions. Our goal was to estimate realistic bounds for lesion detectability for static measurements within 1 to 4 hours between FDG injection and image acquisition. Tumor and normal tissue kinetic model parameters were estimated from dynamic PET studies of patients with early-stage breast cancer. These parameters were used to generate time-activity curves (TACs) for up to 4 hours, for which we assumed both nonreversible and reversible models with different rates of FDG dephosphorylation (k4). For each pair of tumor and normal tissue TACs, 600 PET sinogram realizations were generated, and images were reconstructed using the ordered subsets expectation maximization reconstruction algorithm. Test statistics for each tumor and normal tissue region of interest were output from the computer model observers and evaluated using a receiver operating characteristic analysis, with the calculated area under the curve (AUC) providing a measure of lesion detectability. For the nonreversible model (k4 = 0), the AUC increased in 11 of 23 (48%) patients for 1 to 2 hours after the current standard postradiotracer injection imaging window of 1 hour. This improvement was driven by increased tumor/normal tissue contrast before the impact of increased noise that resulted from radiotracer decay began to dominate the imaging signal. As k4 was increased from 0 to 0.01 min−1, the time of maximum detectability shifted earlier, due to decreasing FDG concentration in the tumor lowering the CNR. These results imply that delayed PET imaging may reveal inconspicuous lesions that otherwise would have gone undetected

Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-Ffluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses-1

<p><b>Copyright information:</b></p><p>Taken from "Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[F]fluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses"</p><p>http://www.biomedcentral.com/1471-2385/7/3</p><p>BMC Nuclear Medicine 2007;7():3-3.</p><p>Published online 3 Jul 2007</p><p>PMCID:PMC1931583.</p><p></p>1 and 7 (1–7 d) and later than one week (>1 wk) after FLT injection. Lines link all values for an individual patient over time. On Figures A & C the means +/- standard deviations for red blood cells (A) and hematocrit (C) are plotted over time. Dotted horizontal lines illustrate the upper and lower normal limits (reference range) for each test

Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-Ffluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses-0

<p><b>Copyright information:</b></p><p>Taken from "Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[F]fluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses"</p><p>http://www.biomedcentral.com/1471-2385/7/3</p><p>BMC Nuclear Medicine 2007;7():3-3.</p><p>Published online 3 Jul 2007</p><p>PMCID:PMC1931583.</p><p></p>�24 h), between day 1 and 7 (1–7 d) and later than one week (>1 wk) after FLT injection. Lines link all values for an individual patient over time. On Figure F (same data as Figure E) the mean +/- standard deviation for albumin is plotted over time. Dotted horizontal lines illustrate the upper and lower normal limits (reference range) for each test

Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-Ffluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses-4

<p><b>Copyright information:</b></p><p>Taken from "Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[F]fluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses"</p><p>http://www.biomedcentral.com/1471-2385/7/3</p><p>BMC Nuclear Medicine 2007;7():3-3.</p><p>Published online 3 Jul 2007</p><p>PMCID:PMC1931583.</p><p></p>�24 h), between day 1 and 7 (1–7 d) and later than one week (>1 wk) after FLT injection. Lines link all values for an individual patient over time. On Figure F (same data as Figure E) the mean +/- standard deviation for albumin is plotted over time. Dotted horizontal lines illustrate the upper and lower normal limits (reference range) for each test

Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-Ffluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses-5

<p><b>Copyright information:</b></p><p>Taken from "Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[F]fluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses"</p><p>http://www.biomedcentral.com/1471-2385/7/3</p><p>BMC Nuclear Medicine 2007;7():3-3.</p><p>Published online 3 Jul 2007</p><p>PMCID:PMC1931583.</p><p></p>1 and 7 (1–7 d) and later than one week (>1 wk) after FLT injection. Lines link all values for an individual patient over time. On Figures A & C the means +/- standard deviations for red blood cells (A) and hematocrit (C) are plotted over time. Dotted horizontal lines illustrate the upper and lower normal limits (reference range) for each test

Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-Ffluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses-2

<p><b>Copyright information:</b></p><p>Taken from "Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[F]fluorothymidine (F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses"</p><p>http://www.biomedcentral.com/1471-2385/7/3</p><p>BMC Nuclear Medicine 2007;7():3-3.</p><p>Published online 3 Jul 2007</p><p>PMCID:PMC1931583.</p><p></p