Tumour Imaging Using an Improved Method of Dtpa-Coupled Monoclonal Antibodies Radiolabelled With Metallic Radionuclides

Epenetos, A. A.; Snook, D.; Hooker, G; Lavender, J. P.; Halnan, K.E.

doi:10.1016/s0140-6736(84)91087-0

Cited by 13 publications

(6 citation statements)

References 7 publications

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“…In, but the former is not readily conjugated with native proteins, and after injection of proteins labeled with "' In there is marked nonspecific uptake of isotope in the liver . This is well known in man (32) and we have encountered the same problem in mice with "'In-SAP labeled by the diethylenetriaminepentaacetic acid method (unpublished observations) .…”

Section: Discussionmentioning

confidence: 53%

Specific localization and imaging of amyloid deposits in vivo using 123I-labeled serum amyloid P component.

Hawkins

Myers

Epenetos

et al. 1988

The Journal of Experimental Medicine

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Highly specific, high-resolution scintigraphic images of amyloid-laden organs in mice with experimentally induced amyloid A protein (AA) amyloidosis were obtained after intravenous injection of 123I-labeled serum amyloid P component (SAP). Interestingly, a much higher proportion (up to 40%) of the injected dose of heterologous human SAP localized to amyloid and was retained there than was the case with isologous mouse SAP, indicating that human SAP binds more avidly to mouse AA fibrils than does mouse SAP. Specificity of SAP localization was established by the failure of the related proteins, human C-reactive protein and Limulus C-reactive protein, to deposit significantly in amyloid and by the absence of human SAP deposition in nonamyloidotic organs. However, only partial correlations were observed between the quantity of SAP localized and two independent estimates, histology and RIA for AA of the amount of amyloid in particular organs. It is not clear which of the three methods used reflects better the extent or clinical significance of the amyloid deposits but in vivo localization of radiolabeled SAP, detectable and quantifiable by gamma camera imaging, is apparently extremely sensitive. These findings establish the use of labeled SAP as a noninvasive in vivo diagnostic probe in experimental amyloidosis, potentially capable of revealing the natural history of the condition, and suggest that it may also be applicable generally as a specific targeting agent for diagnostic and even therapeutic purposes in clinical amyloidosis.

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Section: Discussionmentioning

confidence: 53%

Specific localization and imaging of amyloid deposits in vivo using 123I-labeled serum amyloid P component.

Hawkins

Myers

Epenetos

et al. 1988

The Journal of Experimental Medicine

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“…A similar increase in HIV-1 production occurred when PBL were stimulated with phytohemagglutinin (PHA) (12). The increased production of HIV-1 was not due to HTLV-I-induced T cell transformation, because HTLV-I cell-free virions are generally not infectious (13). Furthermore, no immortalization of PBL incubated with purified HTLV-I virions occurred under these conditions.…”

Section: Hiv-1 Production From Infected Peripheral Bloodmentioning

confidence: 88%

“…Clinical studies suggest that injection of RICs into restricted body cavities such as the peritoneum mnay result in more rapid and specific radiolabeling of intraperitoneal target structures (13). The "'In immunoscintigraphy of mice injected either intravenously or intraperitoneally with the anti-Thy 1.2 IgM RIC shows that both intravenous and intraperitoneal injections resulted in rapid, antigen-specific labeling of the splenic tissue (14).…”

mentioning

confidence: 99%

Radioimmunotherapy with Alpha-Particle-Emitting Immunoconjugates

Macklis

Kinsey

et al. 1988

Science

148

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Alpha particles are energetic short-range ions whose higher linear energy transfer produces extreme cytotoxicity. An alpha-particle-emitting radioimmunoconjugate consisting of a bismuth-212-labeled monoclonal immunoglobulin M specific for the murine T cell/neuroectodermal surface antigen Thy 1.2 was prepared. Analysis in vitro showed that the radioimmunoconjugate was selectively cytotoxic to a Thy 1.2+ EL-4 murine tumor cell line. Approximately three bismuth-212-labeled immunoconjugates per target cell reduced the uptake of [3H]thymidine by the EL-4 target cells to background levels. Mice inoculated intraperitoneally with EL-4 cells were cured of their ascites after intraperitoneal injection of 150 microcuries of the antigen-specific radioimmunoconjugate, suggesting a possible role for such conjugates in intracavitary cancer therapy.

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“…It was stated that the cytotoxicity of Ca-DTPA was caused by interference with the metal requirement of the synthesis of proteins and DNA. It was suggested that the toxic action of both chelating agents In-DTPA Diagnostic Technique was simple and efficient Epenetos et al 1984 Two iron-loaded thalassaemic patients-an 11-year-old boy and a 20-year-old woman Boy treated with ZnDTPA (1 g/day by 12 h s.c. infusion) for a 5-day period, followed by CaDTPA at the same dose for 2 further periods; woman treated with daily oral zinc sulfate and 2 g CaDTPA as a 24-h s.c. infusion Therapeutic Daily infusions in the boy produced symptomatic zinc depletion. ZnDTPA proved ineffective as an iron chelator in both, but zinc balance could be maintained in the woman by combining the use of oral zinc supplements and CaDTPA Pippard et al 1986 12 patients with known or suspected colorectal carcinoma Anti-CEA C110 (antibody)…”

Section: Pentetic Acidmentioning

confidence: 99%

Final Report on the Safety Assessment of Pentasodium Pentetate and Pentetic Acid as Used in Cosmetics

Benes¹,

Burnett²

2008

Int J Toxicol

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Pentasodium Pentetate and Pentetic Acid function as chelating agents in cosmetics. Pentasodium Pentetate is readily soluble in water, but the corresponding free acid is not. Pentasodium Pentetate is used in almost 400 cosmetic products over a wide range of product categories, although it is mostly used in hair dyes and colors at use concentrations of 0.1% to 1.0%. Pentetic Acid is used in 150 cosmetic products, mostly in hair dyes and colors. Chelating agents are used in cosmetics to remove calcium and magnesium cations, which impede foaming and cleansing performance and which can cause a haze in clear liquids. The acute oral LD(50) of Pentasodium Pentetate in rats was > 5 g/kg. The acute dermal LD(50) of Pentapotassium Pentetate using rats was reported to be > 2 g/kg. The intraperitonal LD(50) of Pentetic Acid was reported to be 585 mg/kg. Short-term studies of the calcium and sodium salts of Pentetic Acid in male mice demonstrated no dose-related toxicity over the dose range of 10, 100, and 250 mg/kg. In a 4-week dermal toxicity study, daily topical application of 0.05% Pentasodium Pentetate to shaved and abraded rabbit skin produced moderate erythema after the first week and throughout the study, but no systemic toxicity. Pentasodium Pentetate or Pentapotassium Pentetate applied to intact albino rabbit skin were not irritating. A 40% solution of Pentapotassium Pentetate was not sensitizing in a guinea pig maximization test. The no observed adverse effect level (NOAEL) for rats given 40% Pentapotassium Pentetate by oral gavage was reported to be 83 mg/kg day(-1). Subchronic inhalation evaluation of a bath freshener containing 0.05% or 0.09% Pentasodium Pentetate using albino rats determined that there was no cumulative systemic toxicity attributable to the ingredient at either concentration. The no observed effect level (NOEL) for maternal toxicity in pregnant rats was 400 mg/kg body weight and for fetal toxicity was 100 mg/kg body weight. Another reproductive toxicity study evaluated Pentetic Acid-Zn with and without sodium chloride in pregnant C57/B1 Dougherty mice. No toxicity was found without added sodium chloride. Pentapotassium Pentetate was not mutagenic in an Ames test, with or without metabolic activation. The same material tested in Chinese hamster ovary cells was not clastogenic. Calcium Pentetate at 1.351 microg/ml produced a statistically significant increase in the number of sister-chromatid exchanges. Pentasodium Pentetate is nonirritating to moderately irritating, but not a sensitizer in clinical tests. A human comedogenicity (acne promotion) test using Pentasodium Pentetate found no effect. Although data are lacking on the dermal penetration of these two ingredients, other chelating agents such as EDTA do not penetrate the skin, so it is likely that Pentasodium Pentetate and Pentetic Acid also would not penetrate. The high water solubility of Pentasodium Pentetate and the low water solubility of Pentetic Acid also support that their dermal penetration will be low. Other chelating agents, inclu...

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Tumour Imaging Using an Improved Method of Dtpa-Coupled Monoclonal Antibodies Radiolabelled With Metallic Radionuclides

Cited by 13 publications

References 7 publications

Specific localization and imaging of amyloid deposits in vivo using 123I-labeled serum amyloid P component.

Specific localization and imaging of amyloid deposits in vivo using 123I-labeled serum amyloid P component.

Radioimmunotherapy with Alpha-Particle-Emitting Immunoconjugates

Final Report on the Safety Assessment of Pentasodium Pentetate and Pentetic Acid as Used in Cosmetics

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