• Title/Summary/Keyword: Targeted Alpha Therapy

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211At and 211At-labeled radiopharmaceuticals for targeted alpha therapy

  • Kang, Choong Mo;Lee, Kyo Chul;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.4 no.2
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    • pp.99-105
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    • 2018
  • $^{211}At$ is an alpha emitting radionuclide, which can be produced using cyclotron with alpha beam. In addition, its strong linear energy transfer and iodine-like chemistry make that $^{211}At$ is one of the most attractive radionuclide in the field of targeted alpha therapy. In this review, production, labeling, and radiopharmaceuticals of $^{211}At$ will be discussed.

Targeted alpha therapy (TAT) for cancer using metallic radioisotopes

  • Kang, Chi Soo;Lee, Kyo Chul;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.5 no.2
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    • pp.135-144
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    • 2019
  • Targeted alpha therapy (TAT) based on metallic radionuclides has attracted a lot of attention lately due to its impressive therapeutic efficacy displayed in couple of clinical studies for cancer. Representative metallic radionuclides emitting alpha-particle include 225Ac, 213Bi, and 227Th, and there have been variety of TAT formulations based on different targeting moiety and chelating agents. In this review, we introduce strategies to label metallic radioisotopes with biomolecules and look at some of recent preclinical and clinical results of TAT for cancer.

Clinical Review of the Current Status and Utility of Targeted Alpha Therapy (표적 알파 치료의 현황 및 유용성에 대한 임상적 고찰)

  • Sang-Gyu Choi
    • Journal of radiological science and technology
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    • v.46 no.5
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    • pp.379-394
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    • 2023
  • Targeted Alpha Therapy (TAT) is a new method of cancer treatment that protects normal tissues while selectively killing tumor cells using high cytotoxicity and short range of alpha particles, and target alpha therapy is a highly specific and effective cancer treatment strategy, and its potential has been proven through many clinical and experimental studies. This treatment method accurately delivers alpha particles by selecting specific molecules present in cancer tissue, which has an effective destruction and tumor suppression effect on cancer cells, and one of the main advantages of target alpha treatment is the physical properties of alpha particles. Alpha particles have a very high energy and short effective distance, interacting with target molecules in cancer tissues and having a fatal effect on cancer cells, which is known to cause DNA damage and cell death in cancer cells. TAT has shown positive results in preclinical and clinical studies for various types of cancers, especially those that resist or are unresponsive to existing treatments, but there are several challenges and limitations to overcome for successful clinical transition and application. These include the provision and production of suitable alpha radioisotopes, optimization of target vectors and delivery formulations, understanding and regulation of radiological effects, accurate dosage calculation and toxicity assessment. Future research should focus on developing new or improved isotopes, target vectors, transfer formulations, radiobiological models, combination strategies, imaging techniques, etc. for TAT. In addition, TAT has the potential to improve the quality of life and survival of cancer patients due to the possibility of a new treatment for overcoming cancer, and to this end, prospective research on more carcinomas and more diverse patient groups is needed.

Recent Progress in Alpha-emitting Radiopharmaceutical Development for Clinical Application

  • Choong Mo Kang;Yearn Seong Choe
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.8 no.2
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    • pp.157-166
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    • 2022
  • Targeted alpha therapy began to be applied to the treatment of late-stage cancer patients because of its dramatic therapeutic efficacy in patients who have no responses with beta-emitting radiopharmaceuticals. However, its strong cytotoxicity may cause side effects due to undesirable uptake in non-target tissues. In order to use alpha-emitting radiopharmaceuticals for early-stage patients as well as late-stage cancer patients, therefore, modifications on their chemical structures are required. In this review, the recent progress in the development of alpha-emitting radiopharmaceuticals is discussed.

Super-spatial resolution method combined with the maximum-likelihood expectation maximization (MLEM) algorithm for alpha imaging detector

  • Kim, Guna;Lim, Ilhan;Song, Kanghyon;Kim, Jong-Guk
    • Nuclear Engineering and Technology
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    • v.54 no.6
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    • pp.2204-2212
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    • 2022
  • Recently, the demand for alpha imaging detectors for quantifying the distributions of alpha particles has increased in various fields. This study aims to reconstruct a high-resolution image from an alpha imaging detector by applying a super-spatial resolution method combined with the maximum-likelihood expectation maximization (MLEM) algorithm. To perform the super-spatial resolution method, several images are acquired while slightly moving the detector to predefined positions. Then, a forward model for imaging is established by the system matrix containing the mechanical shifts, subsampling, and measured point-spread function of the imaging system. Using the measured images and system matrix, the MLEM algorithm is implemented, which converges towards a high-resolution image. We evaluated the performance of the proposed method through the Monte Carlo simulations and phantom experiments. The results showed that the super-spatial resolution method was successfully applied to the alpha imaging detector. The spatial resolution of the resultant image was improved by approximately 12% using four images. Overall, the study's outcomes demonstrate the feasibility of the super-spatial resolution method for the alpha imaging detector. Possible applications of the proposed method include high-resolution imaging for alpha particles of in vitro sliced tissue and pre-clinical biologic assessments for targeted alpha therapy.

Review on Targeted Treatment of Patients with Advanced-Stage Renal Cell Carcinoma: A Medical Oncologist's Perspective

  • Tanriverdi, Ozgur
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.609-617
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    • 2013
  • Renal cell carcinomas make up 3% of all cancers and one in four patients is metastatic at time of diagnosis. This cancer is one of the most resistant to cytotoxic chemotherapy. Studies have shown that the efficiency of interferon-alpha and/or interleukin-2 based immune therapies is limited in patients with metastatic renal cell carcinoma but latest advances in molecular biology and genetic science have resulted in better understanding of its biology. Tumor angiogenesis, tumor proliferation and metastasis develop by the activation of signal message pathways playing a role in the development of renal cell carcinomas. Better definition of these pathways has caused an increase in preclinic and clinical studies into target directed treatment of renal cell carcinoma. Many recent studies have shown that numerous anti-angiogenic agents have marked clinical activity. In this article, the focus is on general characteristics of molecular pathways playing a major role in renal cell carcinoma, reviewing clinical information onagents used in the target directed treatment of metastatic lesions.

PSMA Inhibitors for Nuclear Imaging and Radiotherapy of Prostate Cancer

  • Sajid Mushtaq;Tugsuu Uyanga;Park Ji Ae;Jung Young Kim
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.23-33
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    • 2023
  • Prostate cancer ranks as the world's second most frequently diagnosed cancer among men, and is responsible for the fifth highest number of cancer-related deaths in this population. The development of effective diagnostic and therapeutic approaches for prostate cancer remains a major challenge in the field of oncology. Over the past few years, the prostate-specific membrane antigen (PSMA) has raised as a hopeful tracer for the diagnosis and treatment of prostate cancer.Various radioisotopes, such as 131I, 99mTc, 68Ga, and 177Lu, have been used to label PSMA analogues, with varying degrees of success. Among these, 68Ga-PSMA-11 and 177Lu-PSMA-617 have emerged as the most promising radioligands for clinical use. Recently, researchers have been exploring the use of other radioisotopes, such as 211At, 89Zr, 64/67Cu, and 203/212Pb, for the labeling of PSMA-targeted radioligands. These radioisotopes have unique properties that may offer advantages over existing radioligands, such as longer half-lives, higher specific activities, and different emission profiles. Efforts are currently underway to develop these radiopharmaceuticals and make them more widely available for clinical use. These exciting developments highlight the potential of PSMA-targeted radioligands for the diagnosis and treatment of prostate cancer, and provided significant implications for the management of this disease in the future. The current study aims to provide a comprehensive summary of the latest research and clinical applications of radiolabeled PSMA inhibitors for diagnoses and therapy of prostate cancer, emphasizing the exciting developments in the field and their potential impact on clinical practice.

Indacaterol Inhibits Tumor Cell Invasiveness and MMP-9 Expression by Suppressing IKK/NF-κB Activation

  • Lee, Su Ui;Ahn, Kyung-Seop;Sung, Min Hee;Park, Ji-Won;Ryu, Hyung Won;Lee, Hyun-Jun;Hong, Sung-Tae;Oh, Sei-Ryang
    • Molecules and Cells
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    • v.37 no.8
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    • pp.585-591
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    • 2014
  • The ${\beta}_2$ adrenergic receptor (ADRB2) is a G protein-coupled transmembrane receptor expressed in the human respiratory tract and widely recognized as a pharmacological target for treatments of asthma and chronic obstructive pulmonary disorder (COPD). Although a number of ADRB2 agonists have been developed for use in asthma therapy, indacaterol is the only ultra-long-acting inhaled ${\beta}_2$-agonist (LABA) approved by the FDA for relieving the symptoms in COPD patients. The precise molecular mechanism underlying the pharmacological effect of indacaterol, however, remains unclear. Here, we show that ${\beta}$-arrestin-2 mediates the internalization of ADRB2 following indacaterol treatment. Moreover, we demonstrate that indacaterol significantly inhibits tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ activity by reducing levels of both phosphorylated-IKK and -$I{\kappa}B{\alpha}$, thereby decreasing NF-${\kappa}B$ nuclear translocation and the expression of MMP-9, an NF-${\kappa}B$ target gene. Subsequently, we show that indacaterol significantly inhibits TNF-${\alpha}$/NF-${\kappa}B$-induced cell invasiveness and migration in a human cancer cell line. In conclusion, we propose that indacaterol may inhibit NF-${\kappa}B$ activity in a ${\beta}$-arrestin2-dependent manner, preventing further lung damage and improving lung function in COPD patients.

The Ability of Anti-tumor Necrosis Factor Alpha(TNF-${\alpha}$) Antibodies Produced in Sheep Colostrums

  • Yun, Sung-Seob
    • 한국유가공학회:학술대회논문집
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    • 2007.09a
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    • pp.49-58
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    • 2007
  • Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

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