A three-time-point method for assessing kinetic parameters of ⁶⁴Cu-labeled Ramucirumab trapping in VEGFR-2 positive lung tumors

To describe a three-time-point method for estimating kinetic parameters involved in ⁶⁴Cu-labeled Ramucirumab (⁶⁴Cu-NOTA-RamAb) trapping of VEGFR-2 positive lung tumors.

Positron emission tomography (microPET) data of tumor-bearing mice for ⁶⁴Cu-NOTA-RamAb trapping in VEGFR-2 positive HCC4006 tumor were used, involving tissue activity measurements acquired at 3, 24 and 48 h post-injection, without and with administration of RamAb blocking dose. A kinetic model provided an analytical formula describing the tissue time-activity-curve, involving ⁶⁴Cu-NOTA-RamAb uptake (Ki), release rate constant (k_R) and fraction of free tracer in blood and interstitial volume (F).

Fitting analytical formula outcomes on mean microPET data yielded values of the kinetic parameters: Ki = 0.0314/0.0123 gram of blood per hour per gram of tissue, k_R = 0.0387/0.0313 h^-1 and F = 0.2075/0.2007 gram of blood per gram of tissue, without/with RamAb blocking dose, respectively (R = 0.99999 for the graph displaying microPET versus theoretical data; P < .01).

Three independent kinetic parameters (Ki, k_R and F) can be assessed from three data points acquired at early, mid and late imaging, i.e., at 3, 24 and 48 h post-injection, for further characterization of ⁶⁴Cu-NOTA-RamAb trapping in VEGFR-2 positive lung tumors.