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J Nucl Med. 2008; 49 (Supplement 1):152P
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Instrumentation & Data Analysis: Data Analysis & Management

Cardiac/Small Animal

A compartmental model for kinetics of 64Cu-RGD peptide in mice

Gregory Ferl1, Rebecca Dumont1, Isabel Hildebrandt1, Amanda Armijo1, Roland Haubner2, Wolfgang Weber1 and Sung-Cheng Huang1

1 Molecular and Medical Pharmacology, UCLA, Los Angeles, California; 2 University of Innsbruck, Innsbruck, Austria

604

Objectives: To understand PET measured anti-{alpha}Vβ3-integrin 64Cu-RGD peptide kinetics in mice, we have constructed a compartmental model that can describe kinetics in tumor post IV injection.

Methods: We analyzed 64Cu-RGD peptide 60 min dynamic and 24 hr static follow-up PET scans in 8 tumor bearing SCID mice following a 400 µCi bolus dose using a standard 2-compartment (4k) tissue model with input function calculated by drawing an ROI on the reconstructed PET image in the area corresponding to heart left ventricle. 5 blocking (bl) studies were also considered where tracer was blocked with a cold dose (500x excess hot dose). Patlak & Logan analysis suggested that k4 should be fixed at some constant value (4k-fix). We fitted 2k (k3=k4=0), 3k (k4=0), 4k and 4k-fix models to the PET data and used 2 criteria to determine that 4k-fix is the best model: Akaike Information Criteria and ability of each model to predict tumor concentration of tracer 24 hr post injection.

Results: The 4k-fix model was successfully fitted to dynamic tumor data from all studies. Analysis of specific (sp) and nonspecific (nsp) binding using fitted parameter values shows that the 4k-fix model provided expected results when comparing bl and nbl studies, i.e., Vd,sp [(K1xk3)/(k2xk4)] is much higher than Vd,nsp (K1/k2) in nbl studies (2.2±0.6 vs 0.85±0.14) while Vd,sp and Vd,nsp are about the same in bl studies (0.46±0.16 vs 0.56±0.09). Also, the ratio of static measurements (Tumor60 min/Blood10 min) is highly correlated (RS=0.92) to tumor Vd.

Conclusions: We’ve developed and validated a compartmental model for use with the novel 64Cu-RGD peptide PET tracer and demonstrated its potential as a tool for analysis and design of preclinical and clinical imaging studies.

Research Support: NCI Grant R25-CA098010, HHMI Training Fellowship





This Article
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Ferl, G.
Right arrow Articles by Huang, S.-C.
PubMed
Right arrow Articles by Ferl, G.
Right arrow Articles by Huang, S.-C.