scholarly journals Tumor Metabolism and Blood Flow Changes by Positron Emission Tomography: Relation to Survival in Patients Treated With Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer

2008 ◽  
Vol 26 (27) ◽  
pp. 4449-4457 ◽  
Author(s):  
Lisa K. Dunnwald ◽  
Julie R. Gralow ◽  
Georgiana K. Ellis ◽  
Robert B. Livingston ◽  
Hannah M. Linden ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced ◽  
Standardized Uptake Value ◽  
Advanced Breast ◽  
Emission Tomography ◽  
Mortality Risks ◽  
Positron Emission

Purpose Patients with locally advanced breast carcinoma (LABC) receive preoperative chemotherapy to provide early systemic treatment and assess in vivo tumor response. Serial positron emission tomography (PET) has been shown to predict pathologic response in this setting. We evaluated serial quantitative PET tumor blood flow (BF) and metabolism as in vivo measurements to predict patient outcome. Patients and Methods Fifty-three women with primary LABC underwent dynamic [18F]fluorodeoxyglucose (FDG) and [15O]water PET scans before and at midpoint of neoadjuvant chemotherapy. The FDG metabolic rate (MRFDG) and transport (FDG K1) parameters were calculated; BF was estimated from the [15O]water study. Associations between BF, MRFDG, FDG K1, and standardized uptake value and disease-free survival (DFS) and overall survival (OS) were evaluated using the Cox proportional hazards model. Results Patients with persistent or elevated BF and FDG K1 from baseline to midtherapy had higher recurrence and mortality risks than patients with reductions. In multivariable analyses, BF and FDG K1 changes remained independent prognosticators of DFS and OS. For example, in the association between BF and mortality, a patient with a 5% increase in tumor BF had a 67% higher mortality risk compared with a patient with a 5% decrease in tumor BF (hazard ratio = 1.67; 95% CI, 1.24 to 2.24; P < .001). Conclusion LABC patients with limited or no decline in BF and FDG K1 experienced higher recurrence and mortality risks that were greater than the effects of clinical tumor characteristics. Tumor perfusion changes over the course of neoadjuvant chemotherapy measured directly by [15O]water or indirectly by dynamic FDG predict DFS and OS.

scholarly journals A Simplified in vivo Autoradiographic Strategy for the Determination of Regional Cerebral Blood Flow by Positron Emission Tomography: Theoretical Considerations and Validation Studies in the Rat

1982 ◽  
Vol 2 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Myron D. Ginsberg ◽  
Alan H. Lockwood ◽  
Raul Busto ◽  
Ronald D. Finn ◽  
Cathy M. Butler ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Cerebral Blood Flow ◽  
Animal Studies ◽  
Blood Flow Rate ◽  
Emission Tomography ◽  
Regional Cerebral Blood ◽  
Positron Emission

A simplified mathematical model is described for the measurement of regional cerebral blood flow by positron emission tomography in man, based on a modification of the autoradiographic strategy originally developed for experimental animal studies. A modified ramp intravenous infusion of radiolabeled tracer is used; this results in a monotonically increasing curvilinear arterial activity curve that may be accurately described by a polynomial of low degree (= z). Integrated cranial activity C̄ B is measured in regions of interest during the latter portion of the tracer infusion period (times T1 to T2). It is shown that [Formula: see text] where each of the terms A x is a readily evaluated function of the blood flow rate constant k, the brain:blood partition coefficient for the tracer, the cranial activity integration limits T1 and T2, the coefficients of the polynomial describing the arterial curve, and an iteration factor n that is chosen to yield the desired degree of precision. This relationship permits generation of a table of C̄ B vs. k, thus facilitating on-line computer solution for blood flow. This in vivo autoradiographic paradigm was validated in a series of rats by comparing it to the classical autoradiographic strategy developed by Kety and associates. Excellent agreement was demonstrated between blood flow values obtained by the two methods: CBF in vivo = CBFclassical X 0.99 − 0.02 (units in ml g−1 min−1; correlation coefficient r = 0.966).

Pharmacokinetic Evaluation of N-[2-(Dimethylamino)Ethyl]Acridine-4-Carboxamide in Patients by Positron Emission Tomography

2001 ◽  
Vol 19 (5) ◽  
pp. 1421-1429 ◽  
Author(s):  
Azeem Saleem ◽  
Robert J. Harte ◽  
Julian C. Matthews ◽  
Safiye Osman ◽  
Frank Brady ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Phase I ◽  
Standardized Uptake Value ◽  
Metabolite Profile ◽  
Emission Tomography ◽  
Plasma Metabolites ◽  
Tumor Blood Flow ◽  
Phase I Studies ◽  
Positron Emission

PURPOSE: To evaluate tumor, normal tissue, and plasma pharmacokinetics of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA). The study aimed to determine the pharmacokinetics of carbon-11–labeled DACA ([11C]DACA) and evaluate the effect of pharmacologic doses of DACA on radiotracer kinetics. PATIENTS AND METHODS: [11C]DACA (at 1/1,000 phase I starting dose) was administered to 24 patients with advanced cancer (pre–phase I) or during a phase I trial of DACA in five patients. Positron emission tomography (PET) was performed to assess pharmacokinetics and tumor blood flow. Plasma samples were analyzed for metabolite profile of [11C]DACA. RESULTS: There was rapid systemic clearance of [11C]DACA over 60 minutes (1.57 and 1.46 L·min-1·m-2in pre–phase I and phase I studies, respectively) with the production of several radiolabeled plasma metabolites. Tumor, brain, myocardium, vertebra, spleen, liver, lung, and kidneys showed appreciable uptake of 11C radioactivity. The area under the time-versus-radioactivity curves (AUC) showed the highest variability in tumors. Of interest to potential toxicity, maximum radiotracer concentrations (Cmax) in brain and vertebra were low (0.67 and 0.54 m2·mL-1, respectively) compared with other tissues. A moderate but significant correlation was observed for tumor blood flow with AUC (r = 0.76; P = .02) and standardized uptake value (SUV) at 55 minutes (r = 0.79; P = .01). A decrease in myocardial AUC ( P = .03) and splenic and myocardial SUV ( P = .01 and .004, respectively) was seen in phase I studies. Significantly higher AUC, SUV, and Cmax were observed in tumors in phase I studies. CONCLUSION: The distribution of [11C]DACA and its radiolabeled metabolites was observed in a variety of tumors and normal tissues. In the presence of unlabeled DACA, pharmacokinetics were altered in myocardium, spleen, and tumors. These data have implications for predicting activity and toxicity of DACA and support the use of PET early in drug development.

Tumor metabolism, blood flow changes, and prognosis by positron emission tomography: A prospective cohort of locally advanced breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 506-506 ◽  
Author(s):  
L. Dunnwald ◽  
J. Gralow ◽  
G. Ellis ◽  
R. Livingston ◽  
H. Linden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
Positron Emission Tomography ◽  
Blood Flow ◽  
Tumor Response ◽  
Locally Advanced ◽  
Emission Tomography ◽  
Breast Cancer Patients ◽  
Tumor Blood Flow ◽  
Positron Emission

506 Background: Breast cancer patients with locally advanced tumors receive preoperative chemotherapy to provide early systemic treatment and assess in-vivo tumor response. Positron emission tomography (PET) has been used to follow tumor response to therapy, as pathologic response is predictive of patient outcome. We evaluated the prognostic utility of serial quantitative PET tumor blood flow (BF) and metabolism measurements. Methods: Fifty-five women with a primary diagnosis of locally advanced breast carcinoma (LABC) underwent dynamic [18F]-FDG and [15O]-water PET scans prior to and at midpoint of neoadjuvant chemotherapy. The FDG metabolic rate (MRFDG), transport (K1), and flux (Ki) parameters were calculated, and tumor blood flow was estimated from the [15O]-water study. Associations between tumor BF and MRFDG measurements and disease-free survival (DFS) and overall survival (OS) were evaluated using the Cox proportional hazards model. Results: Patients that had an increase in BF and K1, from baseline to mid-therapy measurements, had elevated recurrence and mortality risks compared to patients that had reductions in BF and MRFDG values. In multivariate analysis, changes in BF and K1 remained independent prognostic indicators of DFS and OS survival. Conclusions: PET measurements of tumor response prior to completion of neoadjuvant chemotherapy were predictive of patient outcome. Patients that failed to have a decline in BF and K1 experienced higher risks of recurrence and mortality that was largely independent of clinical tumor characteristics assessed in this study. These results suggest that tumor perfusion, measured directly by [15O]-water or indirectly by dynamic FDG PET, is highly predictive of outcome in neoadjuvantly treated breast cancer. No significant financial relationships to disclose.

scholarly journals Mapping nephron mass in vivo using positron emission tomography

2020 ◽  
Author(s):  
Edwin J. Baldelomar ◽  
David Reichert ◽  
Kooresh I. Shoghi ◽  
Scott C Beeman ◽  
Jennifer R. Charlton ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Standardized Uptake Value ◽  
Human Kidney ◽  
Clinical Translation ◽  
Emission Tomography ◽  
Positron Emission ◽  
Pet Radiotracers ◽  
The Difference ◽  
Increased Susceptibility

Nephron number varies widely in humans. A low nephron endowment at birth or a loss of functioning nephrons is strongly linked to increased susceptibility to chronic kidney disease. In this work, we develop a contrast agent, RadioCF, to map functioning glomeruli in vivo in the kidney using positron emission tomography (PET). PET radiotracers can be detected in trace doses (<30 nmol), making them useful for rapid clinical translation. RadioCF is formed from cationic ferritin (CF) and with a radioisotope, Cu-64, incorporated into the ferritin core. We show that RadioCF binds specifically to kidney glomeruli after intravenous injection in mice, while radiolabeled non-cationic ferritin, (RadioNF), and free Cu-64 do not. We then show that RadioCF-PET can distinguish kidneys in healthy wild type (WT) mice from kidneys in mice with oligosyndactylism (Os/+), a model of congenital hypoplasia and low nephron mass. Average standardized uptake value (SUV) measured by PET 90 minutes after injection was 21% higher in WT mice than in Os/+ mice, consistent with the higher glomerular density in WT mice. The difference in peak SUV from SUV at 90 minutes correlated with glomerular density in male mice from both WT and Os/+ cohorts (R2 = 0.98). Finally, we used RadioCF-PET to map functioning glomeruli in a donated human kidney. SUV within the kidney correlated with glomerular number (R2= 0.78) measured CF-enhanced magnetic resonance imaging in the same locations. This work suggests that RadioCF-PET appears to accurately detect nephron mass and has the potential for clinical translation.

Sign in / Sign up

Export Citation Format

Share Document