No abstract available.
Radioimmunotherapy

Molecular targeting may be defined as the specific concentration of a diagnostic or therapeutic tracer by its interaction with a molecular species that is distinctly present or absent in a disease state. Monoclonal antibody (mAb) is one of the successful agents for targeted therapy in cancer. To enhance the therapeutic effect, the concept of targeting radionuclides to tumors using radiolabeled mAbs against tumor-associated antigens, radioimmunotherapy, was proposed. The efficacy of radioimmunotherapy, however, has to be further optimized. Several strategies to improve targeting of tumors with radiolabeled mAbs have been developed, such as the use of mAb fragments, the use of high-affinity mAbs, the use of labeling techniques that are stable in vivo, active removal of the radiolabeled mAb from the circulation, and pretargeting strategies. Until now, however, there are many kinds of obstacles to be solved in the use of mAb for the targeted therapy. Major technical challenges to molecular targeting are related to the rapid and specific delivery of tracers to the target, the elimination of unwanted background activity, and the development of more specific targets to create a cytocidal effect. Further development of this field will be determined by success in solving these challenges.
Radioimmunotherapy* ; Radioisotopes

No abstract available.
Excipients* ; Radioimmunotherapy*

Radiotherapy with radioactive-isotopes was used in the treating of some thyroidal diseases, malignant diseases of blood, and cancer… The efficacy of this method is depended on radiation, radiating energy, destiny of in vivo transformation of radioactive-isotopes, half-life disintegration time, and characteristics of treated cells and tissues. Author introduces some diseases treated by radiotherapy such as Basedow’s disease, simple goiter, polycythemia, and chronic disease of white blood cell… In addition author introduces some methods such as treating by radioactive colloid and radioimmunotherapy
Radiotherapy ; Radioimmunotherapy ; Radiation

Successful anticancer strategies require a differential response between tumor and normal tissue (i.e., a therapeutic ratio). In fact, improving the effectiveness of a cancer therapeutic is of no clinical value in the absence of a significant increase in the differential response between tumor and normal tissue. Although radiation dose escalation with the use of intensity modulated radiation therapy has permitted the maximum tolerable dose for most locally advanced cancers, improvements in tumor control without damaging normal adjacent tissues are needed. As a means of increasing the therapeutic ratio, several new approaches are under development. Drugs targeting signal transduction pathways in cancer progression and more recently, immunotherapeutics targeting specific immune cell subsets have entered the clinic with promising early results. Radiobiological research is underway to address pressing questions as to the dose per fraction, irradiated tumor volume and time sequence of the drug administration. To exploit these exciting novel strategies, a better understanding is needed of the cellular and molecular pathways responsible for both cancer and normal tissue and organ response, including the role of radiation-induced accelerated senescence. This review will highlight the current understanding of promising biologically targeted therapies to enhance the radiation therapeutic ratio.
Aging ; Radiobiology ; Radioimmunotherapy ; Signal Transduction ; Tumor Burden

Monoclonal antibodies are designed to bind specifically to certain antigen, give therapeutic effect to the target and to be produced in large scale with homogeneity. The monoclonal antibodies conjugated with radionuclide can deliver therapeutic irradiation to the target, and showed successful results in certain malignancies, which is known as radioimmunotherapy. The target-to-background ratio depends on the antigen expression in the target and normal tissues, which is related to the therapeutic efficacy and toxicity in radioimmunotherapy. For the solid tumor beta-ray energy should be high, but lower beta energy is better for the hematological malignancies. I-131 is widely used in thyroid cancer with low cost and high availability. Labeling monoclonal antibody with I-131 is relatively simple and reproducible. Some preclinical data for the I-131 labeled monoclonal antibodies including acute toxicity and efficacy are available from already published literatures. In KIRAMS, physician sponsored clinical trial protocols using Rituximab, KFDA approved anti-CD20 chimeric monoclonal antibody and I-131 were approved by KFDA and currently are ongoing.
Antibodies, Monoclonal ; Hematologic Neoplasms ; Immunoconjugates* ; Radioimmunotherapy* ; Thyroid Neoplasms ; Rituximab

Tumor interstitial pressure is a fundamental feature of cancer biology. Elevation in tumor pressure affects the efficacy of cancer treatment and results in the heterogenous intratumoral distribution of drugs and macromolecules. Monoclonal antibodies (mAb) play a prominent role in cancer therapy and molecular nuclear imaging. Therapy using mAb labeled with radionuclides—also known as radioimmunotherapy (RIT)—is an effective form of cancer treatment. RIT is clinically effective for the treatment of lymphoma and other blood cancers; however, its clinical use for solid tumor was limited because their high interstitial pressure prevents mAb from penetrating into the tumor. This pressure can be decreased using anti-cancer drugs or additional external therapy. In this paper, we reviewed the intratumoral pressure using direct tumor-pressure measurement strategies, such as the wick-in-needle and pressure catheter transducer method, and indirect tumor-pressure measurement strategies via magnetic resonance.
Antibodies, Monoclonal ; Biology ; Catheters ; Lymphoma ; Methods ; Radioimmunotherapy ; Transducers

PURPOSE: Radiolabeled CEA79.4 antibody has a possibility to be used in radioimmunoscintigraphy or radioimmunotheraphy of cancer. We investigated the in vitro properties and biodistribution of CEA79.4 antibody labeled with Re-188 or Tc-99m. MATERIALS AND METHODS: CEA79.4 was reduced by 2-mercaptoethanol to produce-SH reside, and was labeled with Re-188 or Tc-99m. For direct labeling of Tc-99m, methylene-diphosphonate was used as transchelating agent. CEA79.4 in 50 mM Acetate Buffered Saline (ABS, pH 5.3) was labeled with Re-188, using stannous tartrate as reducing agent. In order to measure immunoreactivity and the affinity constant of radiolabeled antibody, cell binding assay and Scatchard analysis using human colon cancer cells SNU-C4, were performed. Biodistribution study of labeled CEA79.4 was carried out at 1, 14 and 24 hr in ICR mice. RESULTS:. Labeling efficiencies of Tc-99m and Re-188 labeled antibodies were 92.4+/-5.9% and 84.7+/-4.6%, respectively. In vitro stability of Tc-99m-CEA79.4 in human serum was higher than Re-188-CEA79.4. Immunoreactivity and affinity constant of Tc-99m-CEA79.4 were 59.2% and 6.59x109 M-1, respectively, while those of Re-188-CEA79.4 were 41.6% and 4.2x109 M-1, respectively. After 24 hr of administrations of Re-188 and Tc-99m labeled antibody, the remaining antibody, the remaining antibodies in blood were 6.32 and 9.35% ID/g respectively. The biodistribution of each labeled antibody in other organs was similar because they did not accumulate in non-targeted organs. CONCLUSION: In vitro properties and biodistribution of Re-188-CEA79.4 were similar to those of Tc-99m-CEA79.4. It appears that Re-188-CEA79.4 can be used as a suitable agent for radioimmunotherapy.
Animals ; Antibodies ; Colonic Neoplasms ; Humans ; Hydrogen-Ion Concentration ; Mercaptoethanol ; Mice ; Mice, Inbred ICR ; Radioimmunodetection ; Radioimmunotherapy

This review discusses the production of alpha-particle-emitting radionuclides in radioimmunotherapy. Radioimmunotherapy labeled with alpha-particle is expected to be very useful for the treatment of monocellular cancer (e.g. leukemia) and micrometastasis at an early stage, residual tumor remained in tissues after chemotherapy and tumor resection, due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha particle. Despite of the expected effectiveness of alpha-particle in radioimmunotherapy, its clinical research has not been activated by the several reasons, shortage of a suitable a-particle development and a reliable radionuclide production and supply system, appropriate antibody and chelator development. Among them, the establishment of radionuclide development and supply system is a key factor to make an alpha-immunotherapy more popular in clinical trial. Alpha-emitter can be produced by several methods, natural radionuclides, reactor irradiation, cyclotron irradiation, generator system and elution. Due to the sharply increasing demand of 213Bi, which is a most promising radionuclide in radioimmunotherapy and now has been produced with reactor, the cyclotron production system should be developed urgently to meet the demand.
Alpha Particles ; Cyclotrons ; Drug Therapy ; Linear Energy Transfer ; Neoplasm Micrometastasis ; Neoplasm, Residual ; Radioimmunotherapy* ; Radioisotopes*

OBJECTIVE: The aim of the study was to compare transcatheter arterial chemoembolization (TACE) plus ¹³¹I-labelled metuximab with TACE alone for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A comprehensive search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Chinese BioMedical Literature Database with published date from the earliest to February 29th, 2016. No language restrictions were applied, but only prospective randomized controlled trials (RCTs) or non-RCTs were eligible for a full-text review. The primary outcome was the overall survival (OS) and effective rate (the rate of partial atrophy or complete clearance of the tumor lesion). The odds ratios (ORs) were combined using either the fixed-effects model or random-effects model. RESULTS: Eight trials (3 RCTs and 5 non-RCTs) were included, involving a total of 1121 patients. Patients receiving combined therapy of TACE plus ¹³¹I-labelled metuximab showed significant improvement in effective rate {OR = 4.00, (95% confidence interval [CI]: 2.40–6.66), p < 0.001}, 1-year OS (OR = 2.03 [95% CI: 1.55–2.67], p < 0.001) and 2-year OS (OR = 2.57 [95% CI: 1.41–4.66], p = 0.002]. CONCLUSION: TACE plus ¹³¹I-labelled metuximab is more beneficial for treating advanced HCCs than TACE alone in terms of tumor response and OS. Large, multi-center, and blinded randomized trials are required to confirm these findings.
Asian Continental Ancestry Group ; Atrophy ; Carcinoma, Hepatocellular* ; Humans ; Odds Ratio ; Prospective Studies ; Radioimmunotherapy