Positron emission tomographic measurement of blood-to-brain and blood-to-tumour transport of⁸²Rb. I: Error analysis and computer simulations

Abstract

Unidirectional blood-to-brain and blood-to-tumour transport rate constants (K1) for 82Rb (half-life 76 s) and plasma water volume per unit mass of brain/tumour tissue (Vp) can be estimated in vivo using dynamic positron emission tomography (PET). The accuracy of these estimates depends upon the accuracy of PET measurements of regional brain/tumour radioactivity and scintillation well detector measurements of whole-blood radioactivity, which, in turn, depend upon the time course of arterial blood radioactivity. A two-compartmental model has been employed to derive estimates for K1, k2 (efflux rate constant) and Vp from 82Rb/PET data. Errors in these parameter estimates have been studied (1) qualitatively using sensitivity function analysis and (2) quantitatively using computer simulations. The effect of adding a third irreversible compartment and its unidirectional rate constant, k3, has also been investigated. The advantages and disadvantages of bolus injection vs continuous infusion protocols are discussed. Precision in estimated parameters from actual patient data is compared to that obtained from computer simulations in part II of this paper.

Association of 82 Rubidium and 11C-methionine uptake in brain tumors measured by positron emission tomography

“…In this context, fitting the RUB data using a two tissue compartment model does also yield a k3 rate constant which might provide more information on the fate of RUB once it has passed the BBB. However, due to the short physical half life of RUB (82Rubidium, 72 seconds), estimation of k3 has been regarded to result in errors of K1 estimation [22]. This emphazises the possible use of longer lived positron emitting RUB isotopes (e.g.…”

Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: crossing the blood–brain barrier divide

“…82 Rb + is a potassium analogue that also crosses the intact BBB, albeit slowly due to its positive charge and significant hydration. Despite its very short half-life, 82 Rb-PET can be used to rapidly quantify changes in BBB permeability, for example in patients with intracranial tumors [140], and after mannitol-induced BBBD [141]. …”

In vivo CT measurement of blood-brain transfer constant of iopamidol in human brain tumors

“…Nevertheless, k is not sensitive to changes in Cb(t ) [7], only K and Vp can be determined from the model with precision.…”

“…Hawkins et al [3] and Iannotti et al [4] used [6SGa]EDTA and a two-compartment model to measure the bloodbrain transfer constant in brain tumor patients. Dhawan et al [7,8] provided a detailed analysis of the two-compartment model for the measurement of the bloodbrain transfer constant of 82Rb+. Dhawan et al [7,8] provided a detailed analysis of the two-compartment model for the measurement of the bloodbrain transfer constant of 82Rb+.…”