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Special Problems of Internal Radioactive Materials
Published in George W. Casarett, Radiation Histopathology, 2019
Strontium-90 is a beta emitter with a physical half-life of 28 years. Strontium-89 is a beta emitter, with some gamma emission, with a physical half-life of 51 days. Strontium-90 is of great importance as a potential long-term hazard among the fission products released by nuclear explosions and from reactor accidents. Strontium-90 possesses the hazardous combination of a high fission yield, long physical and biological half-life, high absorption rate, and a long residence time in bone. It is a moderately powerful beta emitter. Since it is similar to calcium chemically and with respect to metabolism, it tends to enter the mineral phase of bone, especially where mineralization of new bone or cartilage is taking place. Consequently, although it is not uniformly distributed in the adult skeleton, it tends to be more nearly so in children, in whom new bone is being formed in the process of generalized skeletal growth. The rate of accretion of calcium and therefore of strontium tends to be greater in young growing animals than in adults.
The prostate and seminal vesicles
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
Radiotherapy for symptomatic metastases is an excellent form of palliative treatment, often producing dramatic pain relief in men with hormone-relapsed prostate cancer that can last up to 6 months. When multiple sites are involved, intravenous radiopharmaceuticals such as strontium-89 can be employed. Strontium is a bone-seeking isotope that delivers effective radiotherapy to metastatic areas. It appears to be as effective as hemibody irradiation in the treatment of men with metastatic hormone-relapsed disease; however, the duration of response has been disappointing.
Radiopharmaceutical Therapy of Cancer
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Daniel A. Pryma, Chaitanya R. Divgi
Strontium-89 is a β-emitter with a 50.5-day half-life that behaves in vivo as a calcium ion analog. It is administered intravenously as strontium chloride and is subsequently incorporated into new bone by osteoblasts. It has been shown to palliate pain in up to 80% of patients with painful prostate or breast cancer metastases (19–21). Toxicity is hematologic and generally mild and self-limiting (19–21). The major clinical concern with the use of strontium-89 is that while toxicity is mild, because of the long half-life, the toxicity can be prolonged, entailing potential delay in therapy with (other) hematotoxic therapies.
Combinatorial effect of radium-223 and irreversible electroporation on prostate cancer bone metastasis in mice
Published in International Journal of Hyperthermia, 2021
Raniv D. Rojo, Joy Vanessa D. Perez, Jossana A. Damasco, Guoyu Yu, Song-Chang Lin, Francisco M. Heralde, Nora M. Novone, Elmer B. Santos, Sue-Hwa Lin, Marites P. Melancon
Prostate cancer bone metastasis is unique in that the lesions tend to be bone forming rather than bone lysing [36]. Induction of endothelial-to-osteoblast transition by tumor-secreted bone morphogenetic protein 4 (BMP4) was shown to be one of the mechanisms underlying development of bone-forming metastases in prostate cancer [37]. Prostate cancer-stimulated bone formation has been shown to release factors from bone, termed osteocrines, that activate survival pathways in tumor cells and contribute to resistance to chemotherapies or targeted therapies [37,38]. Radiopharmaceuticals, such as strontium-89, have been used to control prostate tumor-induced osteoblasts, but patients treated with radiopharmaceutics have limited survival benefit [39]. Radium 223 dichloride (Ra-223, Xofigo) is the first alpha-emitting radionuclide approved by the US Food and Drug Administration for men with symptomatic bone metastases and castration-resistant prostate cancer. Ra-223 has been shown to increase the median survival of patients with prostate cancer by 3.6 months and reduce bone pain [40]. Ra-223 acts as a calcium analog and is incorporated into the sites of active mineralization [41]. As a result, Ra-223 concentrates in areas of high bone-forming activity [42]. This results in a much more energetic and localized area of effect [43]. Unlike β-emitters, Ra-223 has a short particle track length [44] and exerts potent cell killing activity through non-reparable double-strand DNA breaks [45]. Its short range causes fewer complications, such as bone marrow suppression or destruction, of adjacent normal tissue than are observed with β-emitters.
Radioactive polymeric nanoparticles for biomedical application
Published in Drug Delivery, 2020
Shentian Wu, Edward Helal-Neto, Ana Paula dos Santos Matos, Amir Jafari, Ján Kozempel, Yuri José de Albuquerque Silva, Carolina Serrano-Larrea, Severino Alves Junior, Eduardo Ricci-Junior, Frank Alexis, Ralph Santos-Oliveira
99mTc stands out for being used in 90% of diagnostic procedures in nuclear medicine (Costa et al., 2019). Nano radiopharmaceuticals based on 99mTc and, more recently, rhenium-186 have become essential tools for the diagnosis and therapy of various diseases or dysfunctions of organs and systems within the human body (Dewanjee, 1990; Hua et al., 2005; Costa et al., 2019). The development of nano radiopharmaceuticals provides a new paradigm for nuclear medicine and radioprotection and dosimetry and emerges as a viable alternative to tumor treatment and diagnosis (Garnett and Kallinteri, 2006). In addition, other radiopolymers including strontium-89 chloride, samarium-153 lexidronam, and rhenium-186 etidronate, are currently used in the treatment of bone pain caused by bone metastasis. Although there are several differences between these radiopharmaceuticals, including physical half-life, beta energy, penetration range, and biochemical features, there is no reported advantage in the increased response rate (Paes and Serafini, 2010). Technetium-99m is the most widely used SPECT radionuclide because it has optimal imaging characteristics, including a short half-life of 6.0 h and a γ emission of 140 keV for SPECT imaging applications. NPs have been labeled with 99mTc to increase understanding of their biodistribution characteristics. Radiolabeling with 99mTc is usually accomplished using two different methods (Sogbein et al., 2014). In the case of polymeric NPs, radiolabeling was performed through a direct labeling approach and a nicotinic acid (HYNIC)-type ligand system was used for labeling with 99mTc (Kovacs et al., 2014).
Emerging treatment options for prostate cancer
Published in Expert Review of Anticancer Therapy, 2023
Mohammad Atiq, Elias Chandran, Fatima Karzai, Ravi A. Madan, Jeanny B. Aragon-Ching
Radiopharmaceutical therapy has largely been composed of the alpha emitter Radium 223 dichloride. Radium 223 dichloride was the first-in-class alpha-emitting particle that showed improvement in OS in the treatment of mCRPC based on the ALSYMPCA trial [26]. Currently, Radium 223 dichloride is utilized in mCRPC patients with symptomatic bone metastases. Beta emitters have been used in mCRPC for many years in the form of samarium-153 and strontium-89. However, their role had only been in palliation for painful bone metastases as neither provided survival benefit [27,28]. The most recent advancement in radioligand therapy has been with beta emitters, specifically lutetium-177 (177Lu), which has been combined with prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein specifically expressed in prostate cancer cells. TheraP, a phase II study that compared 177Lu-PSMA-617 to cabazitaxel in patients with mCRPC, showed a higher percentage of patients with PSA responses (defined as reductions of at least 50% from baseline) in the lutetium-treated group [29]. This suggested that 177Lu-PSMA-617 may have a role as an alternative to cabazitaxel in mCRPC. Adverse events (AEs) of particular interest in this study include dry mouth, dry eyes, diarrhea, thrombocytopenia, and neuropathy. Dry mouth and dry eyes were seen in 60% and 30% of the patients treated with lutetium as compared to 21% and 4%, respectively, of patients treated with cabazitaxel. This was all grade 1–2 with no grade 3–4 events seen for either treatment with regard to these AEs. Diarrhea was seen in approximately triple the percentage of patients receiving cabazitaxel as compared to lutetium, but again this was mostly grade 1–2. Thrombocytopenia was not only more frequent in lutetium but also more severe as 11% of patients treated with lutetium experienced this at grade 3–4 compared to none of the patients treated with cabazitaxel. Neuropathy, a known possible AE of taxane chemotherapy, occurred in 26% of patients treated with cabazitaxel as compared to lutetium, which is important in a population that may have residual neuropathy from prior taxane treatment. The phase III VISION trial enrolled patients with mCRPC after failure from at least one prior ARPI and one taxane treatment and compared 177Lu-PSMA-617 to SOC therapy. The improvement in OS in the 177Lu-PSMA-617 arm (median OS 15.3 vs. 11.3 months, HR 0.62, 95% CI, 0.52–0.74) led to U.S. FDA approval in March 2022 in this setting [30].