Positron emission tomographic measurement of blood‐to‐brain and blood‐to‐tumor transport of ⁸²Rb: The effect of dexamethasone and whole‐brain radiation therapy

Abstract

Unidirectional blood-to-brain and blood-to-tumor transport rate constants for rubidium 82 were determined using dynamic positron emission tomography in patients with primary or metastatic brain tumors. Regional influx rate constants (K1) and plasma water volume (Vp) were estimated from the time course of blood and brain radioactivity following a bolus injection of tracer. Eight patients were studied before and 24 to 72 hours after treatment using pharmacological doses of dexamethasone, and 6 additional patients with metastatic brain tumors were studied before and within 60 to 90 minutes after 200- to 600-rad whole-brain radiation therapy. Steroid treatment was associated with a 9 to 48% decrease in tumor K1 and a 21% mean decrease in tumor Vp. No consistent changes in K1 or Vp were observed in control brain regions. Tumor K1 and Vp did not increase in patients undergoing whole-brain radiation therapy, all of whom were taking dexamethasone at the time of study. These data suggest that corticosteroids decrease the permeability of tumor capillaries to small hydrophilic molecules (including those of some chemotherapeutic agents) and that steroid pretreatment prevents acute, and potentially dangerous, increases in tumor capillary permeability following cranial irradiation.

Effect of steroids on iopamidol blood-brain transfer constant and plasma volume in brain tumors measured with X-ray computed tomography

“…Consequently, the mean K of tumor in the present patient study (both before and after treatment) was about 3 times higher than the two values cited above. The decrease in tumor K after dexamethasone therapy in this study agreed with the data measured with 82Rbt and PET [2,3]. Our data support the view that corticosteroids decrease the tumor capillary permeability to small hydrophillic molecules and hence have an antiedema effect.…”

“…Nakagawa et al [1] showed that dexamethasone reduced the K of 125I Albumin and Vp in RG-2 glioma in rats. Jarden showed a time course of reduction in K of 82+Rb and Vp in human brain tumors at 6 and 24 hours after intravenous injection of dexamethasone using positron emission tomography (PET) [2,3].…”

Corticosteroids inhibit the generation of lymphokine-activated killer activity in vitro

“…Although this 'vasogenic' cerebral edema can be reduced or controlled to some extent by corticosteroid medications, tumor-associated edema remains a major cause of morbidity and mortality [14,22,33]. Dexamethasone and methylprednisolone are the most commonly used steroids in the neurosurgical setting [4] and, while their exact mechanism of action on cerebral edema is unclear, it has been postulated that they decrease blood-brain and blood-tumor vascular permeability, constrict cerebral vessels, alter transport of sodium, potassium, and water across the endothelial plasmalemma or capillary-glial interface, and stabilize lysosomal membranes [14,21,24,45]. Also, by reducing the extracellular space in the tumor and adjacent brain, steroids indirectly increase the resistance to fluid flow through the brain, reducing the convective spread of plasma-derived edema fluid.…”

Dexamethasone effects on vascular volume and tissue hematocrit in experimental RG-2 gliomas and adjacent brain

“…These are glucocortieoid receptors in botch normal brain [2] and brain tumors [3,4]. Among the published effects o f corticosteroids on brain tumors must be listed changes in cellular proliferation [5], tumor blood flow [6], tumor capillary permeability [7] and energy metabolism [6,8], besides the well known reduction of tumor-associated brain edema [1]. The numerous biological perturbations caused by corticosteroids make it difficult to interpret experimentalobservations in terms of a direct effect on a single biological process.…”