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Radiopharmaceuticals for Radionuclide Therapy
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Meltem Ocak, Emre Demirci, Jessie R. Nedrow, Rebecca Krimins
Yttrium-90 (T1/2=64.2 h) is a therapeutic radionuclide that emits a β-particle with a mean energy of 0.94 MeV and an average tissue penetration range of 2.5 mm. The selective targeting of Yttrium-90-TARE was first reported by Dr. Irving Ariel. In his study, patients with primary pancreatic and liver cancers were treated with 90Y-labeled ceramic microspheres injected intra-arterial at either the celiac axis or hepatic artery. The study concluded that the complications were minimal, and a significant number of patients experienced palliative effects as well as a few patients appearing to have increased survival [19]. Furthermore, the results were supportive of the continuation of exploring the use of Yttrium-90 for TARE. Yttrium-90 TARE agents are today still utilizing microspheres, which are either glass-based (Thrashers) or resin-based (SIR-Spheres) [20, 21]. Both TARE agents are FDA approved as devices under the humanitarian device exemption. Clinical trials mainly throughout the 1990s demonstrated that these agents were safe and effective in HCC (Thrashers) and metastatic colorectal cancer (SIR-Spheres) leading to their FDA approval in the late 1990s and early 2000s.
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Initial clinical trials of the Yttrium-90-labeled mAb gave promising results. Patients underwent surgery followed by chemotherapy, and then waited for some time before receiving pemtumomab. Those who received the agent 4–6 weeks after their chemotherapy, and at a time when they had no evidence of disease, survived longer than patients who only received surgery and chemotherapy. In fact, five-year survival data on patients in a Phase II trial surpassed any previously reported therapy for the treatment of ovarian cancer, which led to its designation of an “orphan drug” by the EU regulator. This led to a multinational Phase III clinical trial to evaluate pemtumomab in a much wider setting using a greater number of patients. Unfortunately, the results of this trial, published in 2004, suggested that the benefits to patients were not significant enough to warrant continued development.
Hepatocellular Carcinoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Daniel H. Palmer, Philip J. Johnson
Radio-isotopes can be delivered via the hepatic artery using yttrium-90-labeled microspheres, so-called selective internal radiotherapy (SIRT). Yttrium-90 is a beta emitter with short tissue penetration, which may reduce the risk of radiation hepatitis. In patients receiving doses in excess of 120 Gy, median survival was 15 months, with no evidence of radiation hepatitis, even in cirrhotic patients.112 These procedures are associated with a risk of lung toxicity if there is extensive arteriovenous shunting in patients with cirrhosis, and an assessment of the degree of shunting should be made prior to treatment.
Foreign body granuloma reaction following SIRT mimicking peritoneal metastases: a word of caution
Published in Acta Chirurgica Belgica, 2020
Edward Willems, Bart Smet, Franceska Dedeurwaerdere, Mathieu D’Hondt
A 64-year old woman was diagnosed with an unresectable intrahepatic cholangiocarcinoma (iCCA) of the left liver expanding to the anterior sector of the right liver and even to the posterior sector of the right liver, leaving only parts of segments VI and VII tumor free. However, the volume of the unaffected liver was too small to allow for a left trisectionectomy. CT-guided punction of enlarged lymph nodes in the liver hilum showed no arguments for malignancy. She was treated with upfront chemotherapy (cisplatinum–gemcitabine). After six courses of chemotherapy, she was reevaluated with CT abdomen, which showed a stable disease. At the multidisciplinary tumor board, selective internal radiation therapy (SIRT) was suggested in an attempt to obtain regression of the lesion and hypertrophy of the unaffected liver segments, which could possibly lead to a resectable situation. Work-up with digital subtraction angiography did not reveal any shunting to the lung or extrahepatic tissues. During the SIRT procedure, yttrium-90 particles were injected in the left hepatic artery and the artery to segments V and VIII. In this way, no microspheres were injected in segments VI and VII. The procedure and postprocedural recovery were uneventful.
Sorafenib: key lessons from over 10 years of experience
Published in Expert Review of Anticancer Therapy, 2019
Bernard Escudier, Francis Worden, Masatoshi Kudo
For over 10 years after its approval for the first-line treatment of advanced HCC, sorafenib remained the only approved systemic treatment available with a clinically significant benefit in OS in this setting [41,42]. The most recent candidate to fail to show an improvement over sorafenib is selective internal radiation therapy with yttrium-90 (Y-90). Two randomized controlled trials evaluating sorafenib versus Y-90 in patients with advanced HCC (the SARAH trial in Europe and the SIRveNIB trial in Asia-Pacific) failed to show improvement in OS compared with sorafenib [63,64]. Y-90 has been evaluated further following sorafenib in the SORAMIC study in patients with HCC who are either ineligible or have failed prior TACE [65]. The final intention-to-treat analysis showed that the addition of Y-90 to sorafenib did not result in a significant improvement in OS compared with sorafenib alone (Table 2).
Mechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications
Published in International Journal of Radiation Biology, 2018
Masoud Najafi, Elahe Motevaseli, Alireza Shirazi, Ghazale Geraily, Abolhasan Rezaeyan, Farzad Norouzi, Saeed Rezapoor, Hamid Abdollahi
In addition to external radiotherapy, gastrointestinal injury is an important side effect of internal radiation therapy, systemic chemotherapy and chemoradiation therapy for hepatic tumor (Chon et al. 2011). Selective internal radiation therapy (SIRT) by yttrium-90 (Y-90) can provide more effective treatment and less side effects compared to external beam radiation, while selectively providing local irradiation to the tumor or metastases. However, this protocol may cause gastrointestinal ulcer, cholecystitis, pancreatitis, bone marrow toxicity, and inflammation. Gastrointestinal complications are the most common complications compared to other organs that have been reported (Crowder et al. 2009). Mucosal ulceration caused by Y-90 is seen as necroinflammatory slough associated with granulated tissue that occurs mostly in the gastric antrum, pylorus, and duodenum (Konda et al. 2009; Zimmermann et al. 2009; Omed et al. 2010). Evidences have revealed that these side effects typically are caused by significant inflammatory responses (Naymagon et al. 2010). Argon plasma coagulation and administration of growth hormone and oral prednisolone (an anti-inflammatory drug) have shown ability to control bleeding caused by radiation-induced gastritis (Shukuwa et al. 2007; Zhang et al. 2012; Yun et al. 2015; Zhang et al. 2015).