The in vivo uses of streptavidin and biotin: a short progress report

Dj, Hnatowich

doi:10.1097/00006231-199408000-00001

Cited by 13 publications

(6 citation statements)

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“…With few exceptions (2,3), pretargeting has been achieved through the use of (strept)avidin and biotin (4)(5)(6)(7). Mathematical modeling of pretargeting has shown clearly the importance to pretargeting of high affinities between the molecular pair employed (8).…”

Section: Introductionmentioning

confidence: 99%

Pretargeting with Amplification Using Polymeric Peptide Nucleic Acid

Chang

Zhang

et al. 2001

Bioconjugate Chem.

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One goal of this investigation was to develop a polymer conjugated with multiple copies of peptide nucleic acid (PNA) and with pharmacokinetic properties suitable for applications in vivo. The second goal was to establish whether the multiple copies of PNA on the polymer could be targeted by hybridization in vitro and in vivo with (99m)Tc-labeled complementary PNA (cPNA). If successful, this approach could then be considered in further investigations as an alternative to existing pretargeting approaches because of the potential for signal amplification in the target. A 80 KDa poly(methyl vinyl ether-alt-maleic acid) (PA) polymer was conjugated with multiple copies of PNA and with multiple copies of poly(ethylene glycol) (PEG) by reacting the NHS derivative of PA with the amine derivatives of PNA and PEG. Using (99m)Tc-MAG(3)-cPNA, targeting of PNA-PA-PEG was studied in vitro and in vivo in inflammation and tumor mouse models, in both cases relying upon nonspecific diffusion for localization. In addition, cPNA-avidin was considered as a clearing agent with biotinylated PNA-PA-PEG. About 80 PNAs could be conjugated to PA provided that about 200 PEGs were also conjugated to raise the aqueous solubility of the PNA-PA-PEG polymer lowered by the addition of the PNAs. About 70% of the PNAs on this polymer in vitro either in solution or attached to beads could be successfully targeted with (99m)Tc-cPNA. In both the inflammation and tumor mouse models, between 35 and 60% of these PNAs could be targeted in the lesions. The advantage of amplification was evident when less favorable results were obtained with PNA-PA-PEG conjugated with only six PNAs. We conclude that amplification can be achieved in vivo using polymers of PNA followed by radiolabeled complementary PNA and that the application of pretargeting using polymers of PNA for amplification can improve localization.

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Section: Introductionmentioning

confidence: 99%

Pretargeting with Amplification Using Polymeric Peptide Nucleic Acid

Chang

Zhang

et al. 2001

Bioconjugate Chem.

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“…As mentioned earlier, a prerequisite for pretargeting is that the recognition system must not be prevalent in critical normal tissues. Biotin is quite abundant in normal tissues, because it is an essential cofactor for several enzymes (22); thus, a streptavidin-IgG conjugate can be predisposed to the binding of endogenous biotin before the radiolabeled biotin is given (23). Fortunately, levels of free biotin in humans have been reported to be lower than in many other animals (24); thus, the level of biotin binding by a streptavidin conjugate does not seem to be compromised in patients (23,25); however, mice have substantial stores of assessable biotin, making it necessary when examining streptavidin-IgG conjugates to place mice on a biotin-deficient diet for several days before administering the conjugate to optimize tumor localization of the radiolabeled biotin (26).…”

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confidence: 99%

Improving the Delivery of Radionuclides for Imaging and Therapy of Cancer Using Pretargeting Methods

Sharkey

Karacay

Cardillo

et al. 2005

Clinical Cancer Research

113

102

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The article reviews the background and current status of pretargeting for cancer imaging and therapy with radionuclides. Pretargeting procedures were introduced f20 years ago as an alternative to directly radiolabeled antibodies. Because they were multistep processes, they were met with resistance but have since progressed to simple and improved procedures that could become the next generation of imaging and therapy with radionuclides. The separation of the radiolabeled compound from the antibody-targeting agent affords pretargeting procedures considerable flexibility in the radiolabeling process, providing opportunities for molecular imaging using g-or positron-emitting radionuclides and a variety of h-and a-emitting radionuclides of therapeutic applications. Pretargeting methods improve tumor/ nontumor ratios, exceeding that achieved with directly radiolabeled FabV fragments, particularly within just a few hours of the radionuclide injection. In addition, tumor uptake exceeds that of a FabV fragment by as much as 10-fold, giving pretargeting a greatly enhanced sensitivity for imaging. Advances in molecular biology have led to the development of novel binding proteins that have further improved radionuclide delivery in these systems. Studies in a variety of hematologic and solid tumor models have shown advantages of pretargeting compared with directly radiolabeled IgG for therapy, and there are several clinical studies under way that are also showing promising results. Thus, the next generation of targeting agents will likely employ pretargeting approaches to optimize radionuclide delivery for a wide range of applications.Radiation continues to play an integral role in the management of cancer, from the use of X-rays and computed tomography for detection to the use of external beam and interstitial radiotherapy (brachytherapy and rapid interstitial therapy) for treatment. Nuclear medicine, which involves the use of internally administered radionuclides, traditionally has played a minor role in the management of cancer, initially relying primarily on the use of [ 67 Ga]citrate for lymphoma imaging and 131 INa for thyroid cancer treatment. However, with the advent of positron emission tomography and [ 18 F]deoxyglucose, and thanks to the development of new antibody-guided therapeutics for non-Hodgkin's lymphoma and emerging peptide-targeted therapeutics, the role of nuclear medicine in the management of cancer is increasing (1, 2).Except for 131 INa and radionuclides used for palliation of bone pain that are selectively taken up by their respective tissues, the specificity for cancer of internally administered radionuclides depends on its coupling to a targeting compound. For example, [18 F]deoxyglucose is concentrated in cancers because they are more metabolically active than most other cells in the body and therefore will accrue more deoxyglucose than surrounding cells. Antibodies have been one of the most commonly used targeting agents, with an extensive history spanning over 50 years (3). During this...

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“…The animals were then necropsied 3 h later. The results shown in Figure 8 indicate no improvement in tumor retention compared to the results from animals that did not receive additional StAv, and in fact, at the higher StAv doses, increased uptake of 111 In-DTPA-peptide-biotin was seen in the liver and blood, but more notably, in the kidneys, the major organ where StAv is known to accrete (30). This also occurred in animals that were coinjected with 100 µg of StAv on the day of the StAv-MN-14 injection.…”

Section: Resultsmentioning

confidence: 86%

“…Another important finding was the fact that endogenous biotin levels in the mouse seriously inhibit this approach. Hnatowich et al (30) had brought this problem to attention earlier, but it has not been studied in detail in the literature. On the basis of published levels of biotin in mouse serum, and our in vitro studies showing the full biotin-binding capability of the conjugates, it was assumed that there would be abundant biotin-binding sites on the StAv with the doses administered.…”

Section: Discussionmentioning

confidence: 99%

Development of a Streptavidin−Anti-Carcinoembryonic Antigen Antibody, Radiolabeled Biotin Pretargeting Method for Radioimmunotherapy of Colorectal Cancer. Studies in a Human Colon Cancer Xenograft Model

Karacay

et al. 1997

Bioconjugate Chem.

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Pretargeting methodologies can produce high tumor:blood ratios, but their role in cancer radioimmunotherapy (RAIT) is uncertain. A pretargeting method was developed using a streptavidin (StAv) conjugate of MN-14 IgG, an anti-carcinoembryonic antigen (CEA) murine monoclonal antibody (mab) as the primary targeting agent, an anti-idiotype antibody (WI2 IgG) as a clearing agent, and DTPA- or DOTA-conjugated biotin as the radiolabeled targeting agent. A variety of reagents and conditions were examined to optimize this method. At 3 h, 111In-DTPA-peptide-biotin tumor uptake was 3.9 +/- 0.8% per gram and tumor:blood ratios were > 11:1. By 24 h, this ratio was 178:1, but tumor accretion declined in accordance with the gradual loss of StAv-MN-14 from the tumor. Tissue retention was highest in the liver and kidneys, but their tumor:organ ratios were > 2:1. Dosimetry predicted that radiolabeled MN-14 alone would deliver higher tumor doses than this pretargeting method. Increasing the specific activity and using DOTA-biotin in place of DTPA increased tumor uptake nearly 2-fold, but analysis of StAv-MN-14's biotin-binding capacity indicated over 90% of the initial biotin-binding sites were blocked within 24 h. Animals fed a biotin-deficient diet had 2-fold higher 111In-DOTA-biotin uptake in the tumor, but higher uptake also was observed in all normal tissues. Although exceptionally adept at achieving high tumor:blood ratios rapidly, the tumor uptake of radiolabeled biotin with this pretargeting method is significantly (p < 0.0001) lower than that with a radiolabeled antibody. Endogenous biotin and enhanced liver and kidney uptake may limit the application of this method to RAIT, especially when evaluating the method in animals, but with strategies to overcome these limitations, this pretargeting method could be an effective therapeutic alternative.

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The in vivo uses of streptavidin and biotin: a short progress report

Cited by 13 publications

References 0 publications

Pretargeting with Amplification Using Polymeric Peptide Nucleic Acid

Pretargeting with Amplification Using Polymeric Peptide Nucleic Acid

Improving the Delivery of Radionuclides for Imaging and Therapy of Cancer Using Pretargeting Methods

Development of a Streptavidin−Anti-Carcinoembryonic Antigen Antibody, Radiolabeled Biotin Pretargeting Method for Radioimmunotherapy of Colorectal Cancer. Studies in a Human Colon Cancer Xenograft Model

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