Tissue Response to Iodine-125 Interstitial Brachytherapy of Cerebral Gliomas

Abstract

The purpose of this study was to investigate histopathological changes and the role of the microglia/macrophage cell system in the therapeutic effect of iodine-125 ( 125 I) interstitial brachytherapy on cerebral gliomas. Out of a series of 60 cases harboring cerebral astrocytomas and other brain tumors treated with 125 I interstitial brachytherapy, autopsy material was available in 10 cases between 0.75 and 60 months after irradiation. The patients were treated with 60-Gy maximum doses at the tumor periphery. Besides the routine HE and Mallory's PTAH trichrome staining, immunohistochemical reactions were carried out for CD15, CD31, CD34, CD45, CD68 (PG-M1), CPM, HAM 56 and HLA-DR antigens to study immunological characteristics of the reactive cell population around gliomas after 125 I treatment. The present immunohistochemical study demonstrated that the early lesions following 125 I interstitial brachytherapy of gliomas are characterized by migrating macrophages apparently concerned with the removal of necrotic debris. The established phase of reactive zone around the necrotic center disclosed a narrow inner rim of microglial accumulation, and a broad outer area consisting of astrocytic gliosis, vascular proliferation, activated microglia and infiltration by macrophages. In the burned-out phase, the necrosis undergoes liquefaction, the microglial rim is replaced by end-stage macrophages, and the reactive zone is transformed into astrocytic gliosis, which can be considered as equivalent to scar tissue formed around necrosis outside of the central nervous system.

[18F]Fluoroethyltyrosine–Positron Emission Tomography-Based Therapy Monitoring after Stereotactic Iodine-125 Brachytherapy in Patients with Recurrent High-Grade Glioma

“…A long-lasting temporary increase (up to 2 years) in capillary permeability (in the vicinity of the therapeutic intratumoral radionecrosis) accompanied by variable degrees of vasogenic edema and concomitantly reduced regional cerebral blood flow have been shown to occur [19][20][21] ; correspondingly, gadolinium-enhanced followup MRI indicates the evolution of so-called triple ring formations as early as 3 months after SBT, which usually increase slowly from the center of the implanted radioactive sources to the periphery and might exceed even the initial tumor volume during the first year after implantation. 3,22 Molecular imaging with PET using radiolabeled amino acid analogues, particularly [methyl-11 C]-Lmethionine (MET) and FET, might help overcome the limitations of morphologic imaging methods as the assessment of BTV based on MET-PET and FET-PET is considered to improve the definition of the tumor borders and tumor volume. A MET-PET study showed that in 74% of patients with high-grade glioma, pathologic amino acid uptake was found outside the abnormal contrast enhancement revealed by MRI, whereas in 100% of the patients, the hyperintensity region on T 2 -weighted MRI extended beyond the MET enhancement area.…”

Iodine-125 brachytherapy for brain tumours - a review

“…The reactive zone consists of a narrow inner rim of microglial accumulation and a broader outer area with astrocytic gliosis, vascular proliferation, activated microglia and infiltration by macrophages. In the burned-out phase the necrosis undergoes liquefaction, the microglia rim is replaced by end-stage macrophages and the reactive zone is transformed into astrocytic gliosis equivalent to a scar [55,63]. …”

Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

“…Also suggested by Tsakiris et al, possible involvement of CPM in macrophage lipid regulation probably would occur via the processing of peptides (directly or indirectly) implicated in lipid uptake/influx. Elevated levels of CPM on TAMs were reported earlier in lung adenocarcinoma, necrotic areas of cerebral gliomas after irradiation, and in a case of clear cell RCC with an atypical, sarcoid-like granulomatous reaction (Kovacs et al 2004;Julow et al 2007aJulow et al , 2007bTsakiris et al 2008). Because TAMs accumulate into (tumoral) necrotic core regions, CPM might be implicated in the process of necrotic debris removal (Julow et al 2007a).…”