227Th-EDTMP: A potential therapeutic agent for bone metastasis

Washiyama, Kohshin; Amano, Ryohei; Sasaki, Jun; Kinuya, Seigo; Tonami, Norihisa; Shiokawa, Yoshinobu; Mitsugashira, Toshiaki

doi:10.1016/j.nucmedbio.2004.05.001

Cited by 28 publications

(19 citation statements)

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“…Several studies have shown the successful use of alpha particle-emitting nuclides, such as 211 At, 213 Bi and 227 Th for radionuclide therapy due to their higher liner energy transfer and shorter path length as compared to beta particle-emitting nuclides. [19][20][21] However, one possible issue is the control of the radiation to normal tissues (kidney or bone marrow etc.) due to its high cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

Yoshimoto

Ogawa

Washiyama

et al. 2008

Intl Journal of Cancer

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The a v b 3 integrin plays a pivotal role in angiogenesis and tumor metastasis. Angiogenic blood vessels overexpress a v b 3 integrin, as in tumor neovascularization, and a v b 3 integrin expression in other microvascular beds and organs is limited. Therefore, a v b 3 integrin is a suitable receptor for tumor-targeting imaging and therapy. Recently, tetrameric and dimeric RGD peptides have been developed to enhance specificity to a v b 3 integrin. In comparison to the corresponding monomeric peptide, however, these peptides show high levels of accumulation in kidney and liver. The purpose of this study is to evaluate tumor-targeting properties and the therapeutic potential of 111 In-and 90 Y-labeled monomeric RGD peptides in BALB/c nude mice with SKOV-3 human ovarian carcinoma tumors. DOTA-c(RGDfK) was labeled with 111 In or 90 Y and purified by HPLC. A biodistribution study and scintigraphic images revealed the specific uptake to a v b 3 integrin and the rapid clearance from normal tissues. These peptides were renally excreted. At 10 min after injection of tracers, 111 In-DOTA-c(RGDfK) and 90 Y-DOTA-c(RGDfK) showed high uptake in tumors (7.3 6 0.6% ID/g and 4.6 6 0.8% ID/g, respectively) and gradually decreased over time (2.3 6 0.4% ID/g and 1.5 6 0.5% ID/g at 24 hr, respectively). High tumor-to-blood and -muscle ratios were obtained from these peptides. In radionuclide therapeutic study, multipledose administration of 90 Y-DOTA-c(RGDfK) (3 3 11.1 MBq) suppressed tumor growth in comparison to the control group and a single-dose administration ( The a v b 3 integrin recognizes the amino acid sequence of arginine-glycine-aspartic acid (RGD peptide). On the basis of the RGD peptide, many peptidomimetic compounds and peptides have been designed to antagonize the a v b 3 integrin. 4 These compounds and anti-a v b 3 integrin monoclonal antibodies have been reported to inhibit angiogenesis without affecting preexisting vessels. 2,5,6 Because of its restricted expression, the a v b 3 integrin is an attractive targeting molecule for tumor imaging and therapy, leading to decreased side effects compared to conventional chemotherapy.The expression of the a v b 3 integrin has been reported to be associated with metastatic potential in melanoma, breast cancer, and colon cancer. 7-9 The development of radiopharmaceuticals for targeting the a v b 3 integrin would be clinically beneficial, not only for screening and for treating patients with a v b 3 integrin-positive tumors but also for monitoring therapeutic efficacy.Many RGD peptides labeled with gamma-emitting and positron-emitting nuclides ( 18 F, 64 Cu, 99m Tc, 125 I, etc.) have been reported as angiogenesis-imaging agents. 10 A recent trend in the development of RGD peptides is the multimerization of RGD peptides to improve the high tumor accumulation and retention of RGD peptides. 11 However, this also leads to the enhancement of radioactive accumulation in nontargeted organs such as kidney and liver. 12 Compared with antibody or multimeric RGD peptides, monomeric RGD ...

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Section: Discussionmentioning

confidence: 99%

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

Yoshimoto

Ogawa

Washiyama

et al. 2008

Intl Journal of Cancer

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“…EDTMP has an affinity for the hydroxyapatite in bone matrix, resulting in high uptake and long-term retention of the 153 Sm in bone (27). A review of recent published series (28) demonstrated pain relief with response rates of 40-95%.…”

Section: Discussionmentioning

confidence: 99%

Phase I Trial of Vertebral Intracavitary Cement and Samarium (VICS): Novel Technique for Treatment of Painful Vertebral Metastasis

Ashamalla

Cardoso

Macedon

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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“…Emission of g-photons allows for scintigraphic imaging of both isotopes. Biodistribution of 227 Th-citrate indicates high uptake in the femur and parietal bone (25). 223 Ra is an alkaline earth metal similar to calcium that, like 227 Th, preferentially accumulates in sites of bone mineralization, binding into hydroxyapatite.…”

Section: Atmentioning

confidence: 99%

“…223 Ra is an alkaline earth metal similar to calcium that, like 227 Th, preferentially accumulates in sites of bone mineralization, binding into hydroxyapatite. g-ray spectroscopy of the femur showed that, if released, 223 Ra redistributes to the bone because of the a-recoil energy, resulting in an increased dose to the bone surface (25). The lack of suitable chelating agents to coordinate 223 Ra limits the development of radioconjugates.…”

Section: Atmentioning

confidence: 99%

α-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies—Part 1

et al. 2018

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Learning Objectives: On successful completion of this activity, participants should be able to (1) cite α-emitter families available for therapeutic use and understand their current production limit; (2) consider radiation safety concerns when handling α-emitters; and (3) overcome radiolabeling and daughter redistribution hurdles with the approaches described in this educational review. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through June 2021.With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous radionuclides that decay by α-particle emission, only a few of these can reasonably be exploited for therapeutic purposes. Factors including radioisotope availability and physical characteristics (e.g., half-life) can limit their widespread dissemination. The first part of this review will explore the diversity, basic radiochemistry, restrictions, and hurdles of α-emitters. Radi onuclide strategies for curative therapy, disease control, or palliation are positioned to constitute a major portion of nuclear medicine. The range of available therapeutic radioisotopes, including a, b, or Auger electron emission, has considerably expanded over the last century (1). Matching the particle decay pathway, effective range, and relative biological effectiveness to tumor mass, size, radiosensitivity, and heterogeneity is the primary consideration for maximizing therapeutic efficacy. b-emitting radioisotopes have the longest particle pathlength (#12 mm) and lowest linear energy transfer (LET) (;0.2 keV/mm), supporting their effectiveness in medium to large tumors (Fig. 1). Although the long b-particle range is advantageous in evenly distributing radiation dose in heterogeneous tumors, it can also result in the irradiation of healthy tissue surrounding the tumor site. Conversely, Auger electrons have high LET (4-26 keV/mm) but a limited pathlength of 2-500 nm that restricts their efficacy to single cells, thus requiring the radionuclide to cross the cell membrane and reach the nucleus. Finally, a-particles have a moderate pathlength (50-100 mm) and high LET (80 keV/mm) that render them especially suitable for small neoplasms or micrometastases. A recent clinical study highlighted the ability of a-radiotherapy to overcome treatment resistance to b-particle therapy, prompting a paradigm shift in the approach toward radionuclide therapy (2).For optimized therapeutic efficacy, the a-cytotoxic payload is expected to accumulate selectively in diseased tissue and deliver a suf...

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227Th-EDTMP: A potential therapeutic agent for bone metastasis

Cited by 28 publications

References 20 publications

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

Phase I Trial of Vertebral Intracavitary Cement and Samarium (VICS): Novel Technique for Treatment of Painful Vertebral Metastasis

α-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies—Part 1

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227Th-EDTMP: A potential therapeutic agent for bone metastasis

Cited by 28 publications

References 20 publications

αvβ3 Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

αvβ3 Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

Phase I Trial of Vertebral Intracavitary Cement and Samarium (VICS): Novel Technique for Treatment of Painful Vertebral Metastasis

α-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies—Part 1

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α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide