In mouse models, radiation preferentially damages ECs of the gut microvasculature, suggesting that ECs may represent the principal targets for radiation and that the death of epithelial stem cells may be a secondary event in gastrointestinal (GI) toxicity. Similarly, it has been proposed that tumor cell death in response to radiotherapy may represent a secondary event after the death of ECs. High doses to hyperperfused tissue suggest that vessel XL184 damage may be key to the antitumoral effect of 90Y. Heterogeneous deposition of microspheres results in a
variability of dosimetric considerations. In radioembolization, millions of 90Y sources are infused into the arterial vasculature. To predict ultimate 90Y deposition, a simulation angiogram is performed 1-2 weeks before treatment using 20-100 micron-sized technetium-99m-labeled macroaggregated albumin (Tc-MAA) particles. Planar and
single-photon emission computed tomography (SPECT) gamma-camera imaging are then used to measure hepatopulmonary shunting to determine selleck chemical the average radiation dose that will be delivered to tumor and nontumor areas. There is variability in correlating between Tc-MAA and actual microsphere deposition (Spearman’s correlation: 0.45-0.82). Furthermore, the resulting estimates reflect the average dose for a certain volume and not the actual dose, as calculated for external or interstitial radiotherapy. Historically, activity measured with intraoperative probes did correlate with the actual dose of radiation delivered and with Tc-MAA planar scintigraphy.
Although the threshold absorbed dose resulting in objective tumor response remains a point of debate and depends on tumor type, vascularity, previous systemic agents, and use of radiosensitizers, tumor responses have been reported with doses as low as 40 Gy. These limitations in dosimetry do not impede the clinical use of 90Y. Tumor shrinkage occurs almost invariably after 90Y using the current methods for activity calculation.[8, 13] Research concepts based on tumor and nontumor dosimetry methods applied to Tc-MAA planar and/or SPECT imaging have been proposed and await external validation.[24, 25] As is well known with radiotherapy, Fenbendazole it may take 3-6 months for the optimal response (i.e., size reduction) to manifest; consequently, median time to response is 6.6 (size) and 1.2 months (necrosis).[3, 8, 26] Progression is often the result of new lesions (intra- or extrahepatic) or within the treated area, because microscopic nests of tumor cells are unlikely to have been affected by 90Y given their lack or arterialization. Reported median time to progression (TTP) ranges from 7.9 to 10.0 months (entire cohort) and from 11.8 to 15.5 months for patients with absent portal vein invasion.[3, 27] However, given unpredictable tumor biology, early progression may be anticipated by baseline tumor characteristics (e.g.