Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody

Hird, V.; Maraveyas, Anthony; Snook, D; Dhokia, B; Soutter, W. P.; Meares, Claude F.; Stewart, John S.; Mason, Peter R.; Lambert, H. E.; Epenetos, Agamemnon A.

doi:10.1038/bjc.1993.349

Cited by 144 publications

(67 citation statements)

References 14 publications

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“…Clinically, RAIT is quite effective in the treatment of lymphoma (Denardo et al, 1988;Goldenberg et al, 1991;Kaminski et al, 1993;Press et al, 1989) and is considered a promising adjuvant for treating occult micrometastatic disease (Blumenthal et al, 1992b). Several clinical trials are assessing the potential utility of RAIT for solid tumor therapy Hird et al, 1993;Juweid et al, 1997;Meredith et al, 1992;Murray et al, 1994). To improve the outcome, one must select an appropriate radionuclide based on the size of the lesion(s) to be treated and an appropriate form of Ab such that the biological decay is matched with the physical decay of the nuclide (Wessels and Rogus, 1984;Wheldon et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Application of cytokine intervention for improved radio-antibody dose delivery

et al. 1997

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The goal of our studies was to determine whether administration of IL-1/GM-CSF to mice could reduce radio-antibodyinduced myelosuppression and allow either dose escalation of radio-antibody using 131 The potential efficacy of radiolabeled antibodies as a cancer therapeutic is dependent on the maximal tolerated dose (MTD) that can be achieved and on the frequency at which doses can be administered. Two factors influencing both the MTD and the dose frequency are the radionuclide and the form of immunoglobulin used.A variety of radionuclides are under investigation for radioimmunotherapy (RAIT), and several advantages and disadvantages of each have been reviewed (Goldenberg, 1993). The availability of each radionuclide and the physical characteristics vary, each radionuclide decaying at a characteristic rate, with the release of distinct radio-active emissions and with differences in the distance that their particles travel in tissue. The b decay from 131 I travels a relatively short distance (,1 mm), and its maximum energy of decay is only 806 keV. Other b-emitting radionuclides, such as 90 Y and 188 Re, have a higher maximum energy (2,270 and 2,120 keV, respectively) and diffuse their radiation effect over a larger distance within tissues, having maximum path lengths of up to a few millimeters. The objective in selecting a radionuclide for a particular therapeutic application is to maximize the tumor radiation dose while sparing radiation-sensitive tissues from circulating radiolabeled antibody (Ab). The choice of nuclide, therefore, is in part dependent on (i) tumor size, which affects cross-fire and the energy-absorbed fraction, and (ii) binding heterogeneity (Humm, 1986;Howell et al., 1989). Shorter-range emitters are considered appropriate for smaller tumor masses since they maximize local energy deposition. For larger tumor burdens (diameter .1 cm), they would be unable to produce high enough dose levels in certain regions within the tumor that are antigen-negative or where the Ab is unable to penetrate.Selection of the form of immunoglobulin is another variable to be optimized for effective RAIT. Analysis of the pharmacokinetics of intact Ab and its fragments reveals a shorter plasma half-life (t 1/2 ) and less non-specific retention by non-tumor tissue of bivalent and monovalent fragments (Covell et al., 1986). As a result of the faster clearance rate of fragments, the radiation dose to blood is also much lower than that of the intact Ab. Therefore, a higher dose of radiolabeled fragment can be administered to a mouse (e.g., 1,200 µCi 131 I-F[ab8] 2 vs. 275 µCi 131 I-IgG).Unlike external beam irradiation, radiation energy in RAIT is imparted at a low dose rate over several days to weeks to tissues from internally distributed sources. The total radiation dose delivered and the rate of energy deposition in individual tissues are determined by the biodistribution of the administered radionuclide and the physical characteristics of the emitted particles. Among many influential variables, Ab biodistribution is...

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Section: Discussionmentioning

confidence: 99%

Application of cytokine intervention for improved radio-antibody dose delivery

et al. 1997

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“…This protein is overexpressed on the surface of epithelial tumour cells, including ovarian, gastric, breast, and lung cells. From a Phase II study in women with advanced ovarian cancer, 15 out of 21 women who were in remission at the time of treatment with pemtumomab responded well and 14 patients were still alive more than eight years after the treatment (Hird et al, 1993). Another feasible use of pemtumomab is in a gastric cancer treatment.…”

Section: Pemtumomab (Theragyn)mentioning

confidence: 99%

Therapeutic radionuclides in nuclear medicine: current and future prospects

Yeong

Cheng

2014

J. Zhejiang Univ. Sci. B

156

115

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Abstract:The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ( 131 I), phosphorous-32 ( 32 P), strontium-90 ( 90 Sr), and yttrium-90 ( 90 Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.

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“…A radiolabeled form of this antibody, yttrium-90-muHMFG1, was also examined in subsequent phase I/II and III trials. 57,58 In the phase I/II trial, yttrium-90-muHMFG1 administered intraperitoneally resulted in improved median survival in the women who received this antibody following traditional surgery and platinum-based chemotherapy. 57 However, despite a significant decrease in intraperitoneal disease following treatment, the phase III study failed to demonstrate a survival advantage due to increased extraperitoneal recurrences.…”

Section: Cancer Immunotherapymentioning

confidence: 99%

“…57,58 In the phase I/II trial, yttrium-90-muHMFG1 administered intraperitoneally resulted in improved median survival in the women who received this antibody following traditional surgery and platinum-based chemotherapy. 57 However, despite a significant decrease in intraperitoneal disease following treatment, the phase III study failed to demonstrate a survival advantage due to increased extraperitoneal recurrences. 58 EpCAM is an antigen overexpressed in ovarian cancer, especially in patients with metastatic and recurrent/chemotherapyresistant disease, and is therefore another attractive target for antibody-mediated immunotherapy.…”

Section: Cancer Immunotherapymentioning

confidence: 99%