Radioimmunotherapy (RIT) in Brain Tumors / 대한핵의학회잡지

Annually, the incidence of brain tumors has slightly increased and also the patient prognosis is still disappointing, especially for high-grade neoplasms. So, researchers seek methods to improve therapeutic index as a critical aim of treatment. One of these new challenging methods is radioimmunotherapy (RIT) that involves recruiting a coupling of radionuclide component with monoclonal antibody (mAb) which are targeted against cell surface tumor–related antigens or antigens of cells within the tumor microenvironment. In the context of cancer care, precision medicine is exemplified by RIT; precision medicine can offer a tailored treatment to meet the needs for treatment of brain tumors. This review aims to discuss the molecular targets used in radioimmunotherapy of brain tumors, available and future radioimmunopharmaceutics, clinical trials of radioimmunotherapy in brain neoplasms, and eventually, conclusion and future perspective of application of radioimmunotherapy in neurooncology cancer care.

Measurement of Tumor Pressure and Strategies of Imaging Tumor Pressure for Radioimmunotherapy / 대한핵의학회잡지

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.

Radioimmunotherapy in Head and Neck Cancer / 대한이비인후과학회지

Radioimmunotherapy (RIT) is a therapy that takes advantage of the “cross-fire” effect of emitted radiation by radionuclides conjugated to tumor-directed monoclonal antibodies (mAb) (including those fragments) or peptides. While RIT has been successfully employed for the treatment of lymphoma, mostly with radiolabeled antibodies against CD20 [⁹⁰yttrium (⁹⁰Y)-ibritumomab tiuxetan; Zevalin® and (131)iodine ((131)I)-tositumomab; Bexxar®], its use in solid tumors is more challenging, so far. Immuno-PET, a tool for tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and guide mAbbased therapy. RIT in solid tumors including head and neck cancer may be an alternative treatment with advances in various biological, chemical, and treatment procedures, and it may help to reduce unnecessary exposure and enhance the therapeutic efficacy. Also, immuno-PET based on RIT might play an important role in cancer staging, in patients or targets selection of targeted therapeutics and in monitoring the response of targeted therapeutics as precision medicine. In this review, fundamentals of RIT/immune-PET and current knowledge of the preclinical/clinical trials in RIT for solid tumor including head and neck cancer are reviewed.

Stereotactic Body Radiotherapy: Does It Have a Role in Management of Hepatocellular Carcinoma?

Stereotactic body radiotherapy (SBRT) is a form of radiotherapy that delivers high doses of irradiation with high precision in a small number of fractions. However, it has not frequently been performed for the liver due to the risk of radiation-induced liver toxicity. Furthermore, liver SBRT is cumbersome because it requires accurate patient repositioning, target localization, control of breathing-related motion, and confers a toxicity risk to the small bowel. Recently, with the advancement of modern technologies including intensity-modulated RT and image-guided RT, SBRT has been shown to significantly improve local control and survival outcomes for hepatocellular carcinoma (HCC), specifically those unfit for other local therapies. While it can be used as a stand-alone treatment for those patients, it can also be applied either as an alternative or as an adjunct to other HCC therapies (e.g., transarterial chemoembolization, and radiofrequency ablation). SBRT might be an effective and safe bridging therapy for patients awaiting liver transplantation. Furthermore, in recent studies, SBRT has been shown to have a potential role as an immunostimulator, supporting the novel combination strategy of immunoradiotherapy for HCC. In this review, the role of SBRT with some technical issues is discussed. In addition, future implications of SBRT as an immunostimulator are considered.

Novel biological strategies to enhance the radiation therapeutic ratio

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.

Transcatheter Arterial Chemoembolization Plus ¹³¹I-Labelled Metuximab versus Transcatheter Arterial Chemoembolization Alone in Intermediate/Advanced Stage Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

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.

Is radioimmunotherapy a 'magic bullet'? / 대한혈액학회지

No abstract available.

Yttrium-90 ibritumomab tiuxetan plus busulfan, cyclophosphamide, and etoposide (BuCyE) versus BuCyE alone as a conditioning regimen for non-Hodgkin lymphoma / 대한혈액학회지

BACKGROUND: Radioimmunotherapy agents have a highly significant role in autologous stem cell transplantation as they improve tolerability and increase the efficacy of the conditioning regimen. METHODS: We retrospectively analyzed the efficacy and toxicity of yttrium-90 ibritumomab tiuxetan (Zevalin) combined with intravenous busulfan, cyclophosphamide, and etoposide (Z-BuCyE) compared with those of BuCyE alone followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). The efficacy, toxicity, and engraftment characteristics were compared between 19 patients who received Z-BuCyE and 19 historical controls who received BuCyE. RESULTS: The 2 treatment groups shared similar baseline characteristics. The median time to platelet engraftment (>20x10(9)/L) and neutrophil engraftment (>0.5x10(9)/L) did not significantly differ between the Z-BuCyE group (12 days and 10 days, respectively) and the BuCyE group (12 days and 10 days, respectively). No significant differences were observed between the groups with respect to toxicities and treatment-related mortality. The median follow-up period was 30.4 months, and median event-free survival was generally better in the Z-BuCyE group (12.5 months) vs. the BuCyE group (6.2 months, P=0.236). No significant difference in overall survival between the groups was noted. CONCLUSION: Adding ibritumomab tiuxetan to BuCyE high-dose chemotherapy may benefit patients with relapsed or refractory B-cell NHL with no risk of additional toxicity.

Antibody-drug conjugates and their application in the treatment of hematological malignancies / 药学学报

Monoclonal antibody-targeted therapy has been a hot spot in current clinical cancer treatment. As current antibody drugs have large molecule sizes leading to poor tissue penetration, and high dosage in clinical application leading to high cost, to overcome the problems, the development of new antibody drugs with miniaturization and high potency has become a new trend. In recent years, the conjugates of monoclonal antibodies and cytotoxins, called antibody-drug conjugates (ADCs), have entered the arsenal of anti-cancer drugs, becoming a new format of antibody drugs and attracting extensive attentions. The ADC molecule usually consists of antibody, linker and effector molecule. According to different effector molecules, ADCs can be divided into three categories as chemo-conjugates, immunotoxins and radio-conjugates. When ADC molecules are internalized into cancer cells, cytotoxins will be released by chemical, enzyme degradation or by action of lysosomal proteases, then kill targeted cells by inhibiting protein synthesis, depolymerizing microtubules or breaking double-strand DNA. Recently, two ADC drugs have been approved by the US FDA and more ADC drug candidates are in clinical phase II or III trials which show significantly clinical effects and attracting much attention and competition of pharmaceutical enterprises. In this review, antibody conjugates in the past and present will be summarized and the future development trends and challenges of this type of antibody drugs will be discussed.

Comparative Quantitative Analysis of Cluster of Differentiation 45 Antigen Expression on Lymphocyte Subsets / 대한진단검사의학회지

BACKGROUND: Since the recent introduction of radioimmunotherapy (RIT) using antibodies against cluster of differentiation (CD) 45 for the treatment of lymphoma, the clinical significance of the CD45 antigen has been increasing steadily. Here, we analyzed CD45 expression on lymphocyte subsets using flow cytometry in order to predict the susceptibility of normal lymphocytes to RIT. METHODS: Peripheral blood specimens were collected from 14 healthy individuals aged 25-54 yr. The mean fluorescence intensity (MFI) of the cell surface antigens was measured using a FACSCanto II system (Becton Dickinson Bioscience, USA). MFI values were converted into antibody binding capacity values using a Quantum Simply Cellular microbead kit (Bangs Laboratories, Inc., USA). RESULTS: Among the lymphocyte subsets, the expression of CD45 was the highest (725,368+/-42,763) on natural killer T (NKT) cells, 674,030+/-48,187 on cytotoxic/suppressor T cells, 588,750+/-48,090 on natural killer (NK) cells, 580,211+/-29,168 on helper T (Th) cells, and 499,436+/-21,737 on B cells. The Th cells and NK cells expressed a similar level of CD45 (P=0.502). Forward scatter was the highest in NKT cells (P<0.05), whereas side scatter differed significantly between each of the lymphocyte subsets (P<0.05). CD3 expression was highest in the Th and NKT cells. CONCLUSIONS: NKT cells express the highest levels of CD45 antigen. Therefore, this lymphocyte subset would be most profoundly affected by RIT or pretargeted RIT. The monitoring of this lymphocyte subset during and after RIT should prove helpful.

Comparative Quantitative Analysis of Cluster of Differentiation 45 Antigen Expression on Lymphocyte Subsets / 대한진단검사의학회지

BACKGROUND: Since the recent introduction of radioimmunotherapy (RIT) using antibodies against cluster of differentiation (CD) 45 for the treatment of lymphoma, the clinical significance of the CD45 antigen has been increasing steadily. Here, we analyzed CD45 expression on lymphocyte subsets using flow cytometry in order to predict the susceptibility of normal lymphocytes to RIT. METHODS: Peripheral blood specimens were collected from 14 healthy individuals aged 25-54 yr. The mean fluorescence intensity (MFI) of the cell surface antigens was measured using a FACSCanto II system (Becton Dickinson Bioscience, USA). MFI values were converted into antibody binding capacity values using a Quantum Simply Cellular microbead kit (Bangs Laboratories, Inc., USA). RESULTS: Among the lymphocyte subsets, the expression of CD45 was the highest (725,368+/-42,763) on natural killer T (NKT) cells, 674,030+/-48,187 on cytotoxic/suppressor T cells, 588,750+/-48,090 on natural killer (NK) cells, 580,211+/-29,168 on helper T (Th) cells, and 499,436+/-21,737 on B cells. The Th cells and NK cells expressed a similar level of CD45 (P=0.502). Forward scatter was the highest in NKT cells (P<0.05), whereas side scatter differed significantly between each of the lymphocyte subsets (P<0.05). CD3 expression was highest in the Th and NKT cells. CONCLUSIONS: NKT cells express the highest levels of CD45 antigen. Therefore, this lymphocyte subset would be most profoundly affected by RIT or pretargeted RIT. The monitoring of this lymphocyte subset during and after RIT should prove helpful.

Advances in prostate-specific membrane antigen targeted therapies for prostate cancer / 中华男科学杂志

Prostate-specific membrane antigen (PSMA) is a type II integral membrane glycoprotein, specifically expressed in prostatic epithelial cells and strongly upregulated in prostate cancer. PSMA is also present in the neovasculature of other solid tumors. These findings have spurred the development of PSMA-targeted therapies for prostate cancer, including immunotherapy, radioimmunotherapy, chemotherapy and gene therapy, and initiated the clinical trials of the first-generation products. However, general clinical application of these therapies still requires extensive clinical studies to test their clinical safety, stability and efficacy.

90Yttrium-ibritumomab tiuxetan radioimmunotherapy for refractory follicular lymphoma

This paper aims to discuss the sequential use of rituximab and 90Yttrium-ibritumomab tiuxetan, a novel treatment approach in the management of refractory follicular non-Hodgkin's lymphoma. Radioimmunotherapy (RIT), which combines the benefits of targeted radiation therapy and monoclonal antibody, has significantly increased the response rate well in excess of 50%. This is explained by the inherent radiosensitive nature of lymphoma cells. We present a case of a 56-year-old male with refractory follicular lymphoma. The patient was referred for RIT, the first case in the Philippines. The patient was pretreated with two doses of rituximab followed by an intravenous infusion of 90Y-ibritumomab tiuxetan (Zevalin). Hematologic nadir was reached six weeks following administration of the radioimmunotherapy. During this time, the patient developed melena. Hematologic recovery was noted after three weeks. Re-evaluation with computed tomography three months after treatment showed significant reduction in the tumor bulk and resolution of lymphadenopathies. This report underscores the importance and evolving role of radioimmunotherapy in the management of refractory non-Hodgkin's lymphoma.

mage-Based Assessment and Clinical Significance of Absorbed Radiation Dose to Tumor in Repeated High-Dose (131)I Anti-CD20 Monoclonal Antibody (Rituximab) Radioimmunotherapy for Non-Hodgkin's Lymphoma / 핵의학분자영상

PURPOSE: We assessed the absorbed dose to the tumor (Dosetumor) by using pretreatment FDG-PET and whole-body (WB) planar images in repeated radioimmunotherapy (RIT) with 131I rituximab for NHL. MATERIALS AND METHODS: Patients with NHL (n=4) were administered a therapeutic dose of (131)I rituximab. Serial WB planar images after RIT were acquired and overlaid to the coronal maximum intensity projection (MIP) PET image before RIT. On registered MIP PET and WB planar images, 2D-ROIs were drawn on the region of tumor (n=7) and left medial thigh as background, and Dosetumor was calculated. The correlation between Dosetumor and the CT-based tumor volume change after RIT was analyzed. The differences of Dosetumor and the tumor volume change according to the number of RIT were also assessed. RESULTS: The values of absorbed dose were 397.7+/-646.2cGy (53.0~2853.0cGy). The values of CT-based tumor volume were 11.3+/-9.1 cc (2.9~34.2cc), and the % changes of tumor volume before and after RIT were -29.8+/-44.3% (-100.0%~+42.5%), respectively. Dosetumor and the tumor volume change did not show the linear relationship (p>0.05). Dosetumor and the tumor volume change did not correlate with the number of repeated administration (p>0.05). CONCLUSION: We could determine the position and contour of viable tumor by MIP PET image. And, registration of PET and gamma camera images was possible to estimate the quantitative values of absorbed dose to tumor.

Five year biochemical recurrence-free rate following permanent prostate brachytherapy in patients with clinically localized prostate cancer

OBJECTIVE: This Study was designed to determine the five year biochemical progression free rate of patients with clinically localized prostate cancer stratified to low, intermediate and high risks groups who underwent permanent prostate brachytheraphy.METHODS: Thirty six patients with a mean age of 67 years diagnosed with clinically localized prostate cancer were treated with Iodine-125 permanent prostate brachytherapy from November 2001 to December 2003. Prostate specific antigen (PSA) failure was defined as having more than +2 increase of serum PSA from the nadir, with PSA nadir set at 0.4 ng/ml. The biochemical recurrence-free rate for the overall and the stratified groups were then calculated.RESULTS: Twelve patients were lost to follow up leaving twenty-four subjects in the study. The prescribe minimum dose was 145 grays. Median follow-up was 62 months. The over-all 5 year biochemical recurrence-free rate was 58%. Satisfying these patients into low, intermediate, and high group yielded a progression free rate of 80%, 42%, and 5%, respectively.CONCLUSION: Permanent prostate branchytheraphy is an effective treatment for patients with clinically localized prostate cancers. This reported 5-year biochemical recurrence-free rate at East Avenue Medical Center (EAMC) is comparable with that reported by other centers.

In vitro cytotoxicity of 131I-Rituximab against B-cell lymphoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the specific cytotoxicity of (131)I-Rituximab against CD20-positive B-cell lymphoma cells.</p><p><b>METHODS</b>Rituximab was labeled with (131)I using IODO-GEN method, and the dose-effects of various concentrations of (131)I-Rituximab, (131)I alone and Rituximab in Raji cells were evaluated by MTT assay to determine the optimal dose according to the dose-effect curves. The cytotoxicity of (131)I-Rituximab, (131)I and Rituximab was assessed in CD20-positive Ramos (RA-1) cells, Raji cells and CD20-negative Molt-4 cells according to the changes of the survival rates. Giemsa staining was used to evaluate the antitumor effect of (131)I-Rituximab in Raji cells by measuring the mitosis index (MI).</p><p><b>RESULTS</b>(131)I-Rituximab presented with a dose-dependent cytotoxicity against Raji cells. At the specific activity of 60 microCi/ml, (131)I-Rituximab resulted in significantly higher growth inhibition rate of the cells than Rituximab (P<0.05). The inhibition rate of Raji cells treated with (131)I-Rituximab, (131)I, or Rituximab for 96 h were comparable with the rates in Ramos RA-1 cells, but significantly higher than the rates in Molt-4 cells. The MI values in (131)I-Rituximab group were significantly lower than those in the other groups (P<0.001).</p><p><b>CONCLUSION</b>(131)I-Rituximab can induce specific cytotoxicity against CD20-positive tumor cells, and may potentially serve as an agent for targeted radioimmunotherapy for CD20-positive B-cell lymphoma.</p>

Radionuclide therapy for hepatocellular carcinoma: indication, cost and efficacy.

A large number of patients with hepatocellular carcinoma (HCC) will have large and/or multiple inoperable tumours, precluding percutaneous ablation, such as percutaneous ethanol, acetic acid or hot saline injection, and radiofrequency ablation. Similarly, if the tumour is not accessible percutaneously or the tumour is subcapsular or subdiaphragmatic, percutaneous therapy is ruled out. Many patients will also have associated portal vein thrombosis, making them unsuitable for chemoembolisation, depending upon the level and severity of thrombosis. Such patients can be offered internal radioisotope therapy to prolong their survival and improve the quality of life. The aim of radioisotope therapy is to deliver the radioisotope to the hepatic tumour, where it must reside for a period sufficient to deliver the scheduled dose of radiation. At the same time the amount delivered to the normal liver parenchyma and other organs should be as low as possible. A variety of radioisotopes, such as lodine-131, Yttrium-90, Rhenium-188, Holmium-166 etc. can be used for this purpose and targeting of the therapeutic agent to the tumour may be achieved by 1) direct intra-tumour implantation of the radioisotope, 2) parenteral injection of radiolabelled antibodies specific to HCC antigens (radioimmunotherapy) or, 3) injecting the radioisotope through the hepatic artery directly into the tumour or trans-arterial radioisotope therapy (TART). The radioisotope therapy appears to be a very reasonable and effective therapeutic alternative, a) for the treatment of large inoperable HCC, particularly with portal vein thrombosis, b) treatment of small inoperable tumours unsuitable for percutaneous therapy because of any reason, c) as a neoadjuvant therapy before hepatic transplantation to reduce the risk of recurrence in the graft or before hepatic resection to shrink the tumour size, and d) as an adjuvant therapy, after surgery or percutaneous ablative therapy to reduce the risk of recurrence. Further, it can be very affordable if generator produced Re-188 is used, which appears to be equally or more effective and useful than other currently available radioisotopes. The availability of Re-188 in a generator form makes its storage, transportation, elution and usage very convenient and cost-effective, particularly at remote places and in developing countries. The use of generator also makes Re-188 available on a constant and need to need basis.

Radioimmunotherapy with 131 I-labeled humanized anti-HBsAg Fab and anti-nucleus antigen monoclonal antibody chTNT in nude mice bearing human hepatocellular carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the feasibility and efficacy of radioimmunotherapy with 131 I-labeled humanized anti-HBsAg Fab (131 I-anti-HBsAg Fab) combined with 131 I-labeled anti-nucleus antigen monoclonal antibody chTNT (131 I-chTNT) in nude mice bearing human hepatocellular carcinoma.</p><p><b>METHODS</b>Nude mice bearing subcutaneous human hepatocellular carcinoma xenografts were treated by intratumoral injection of 131 I-anti-HBsAg Fab and/or 131 I-chTNT, and the changes in the tumor size and alterations in the radioactivity concentration in the tumor and non-tumor tissues were observed.</p><p><b>RESULTS</b>The tumor inhibition rate in mice treated with 131 I-anti-HBsAg Fab combined with 131 I-chTNT (73.09%) was significantly higher than that in mice treated with 131 I-anti-HBsAg Fab (47.8%) or 131 I-chTNT (54.26%) alone. Combined treatment also resulted in significantly higher tumor-to-normal radioactivity concentration ratios than the treatment with the single agents.</p><p><b>CONCLUSION</b>Intratumoral injection with 131 I-labeled monoclonal antibodies can increase the radioactivity concentration in the tumor and enhance the efficacy of the radioimmunotherapy in nude mice bearing human hepatocellular carcinoma.</p>

Evaluation of the Radioimmunotherapy Using I-131 Labeled Vascular Endothelial Growth Factor Receptor2 Antibody in Melanoma Xenograft Murine Model / 핵의학분자영상

PURPOSE: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of 131I labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and METHODS: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to 200-250 mm3 in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of 131I-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), 131I-DC101 50 microgram/mouse (group 2), non-labeled DC101 50 microgram/mouse (group 3), 131I-DC101 30 microgram/mouse (group 4) and 15 microgram/mouse (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. RESULTS: In gamma camera images, the uptake of 131I-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of 131I-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. CONCLUSION: These results indicated that delivery of 131I to tumor using Flk-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.

Role of chelates in treatment of cancer.

Chelates are used in cancer as cytotoxic agent, as radioactive agent in imaging studies and in radioimmunotherapy. Various chelates based on ruthenium, copper, zinc organocobalt, gold, platinum, palladium, cobalt, nickel and iron are reported as cytotoxic agent. Monoclonal antibodies labeled with radioactive metals such as yttrium-90, indium-111 and iodine-131 are used in radioimmunotherapy. This review is an attempt to compile the use of chelates as cytotoxic drugs and in radioimmunotherapy.