Further investigations of morpholino pretargeting in mice—establishing quantitative relations in tumor

Liu, Guozheng; He, Jiang; Dou, Shuping; Gupta, Suresh; Rusckowski, Mary; Hnatowich, Donald J.

doi:10.1007/s00259-005-1853-5

Cited by 29 publications

(70 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MORF-MN14 was synthesized using a commercial Hydralink™ method (Solulink Biosciences, San Diego, CA) [15]. The average gpm of MORF-MN14 used in this study was 1.00 ± 0.03 compared to an average gpm of only 0.17 to 0.30 when an earlier method of conjugation was used [9,10]. A new lot of MN14 antibody was used to investigate the influence the dosage of MORF-MN14.…”

Section: Methodsmentioning

confidence: 99%

“…Pretargeting interval-Earlier experience indicated that a pretargeting interval of 2 d was reasonable [10].…”

Section: Timingmentioning

confidence: 99%

“…In the present study, the conjugation of MN14 has been improved by increasing the average number of MORF groups per molecule (gpm) from 0.17-030 in our previous investigations [9,10] to 1.00 using an alternative conjugation method (Hydralink™). The labeling of cMORF with 99m Tc was also improved to obviate the need for post-labeling purification.…”

Section: Introductionmentioning

confidence: 99%

“…In our recent studies [9,10], the pharmacokinetics of both MORF-MN14 and labeled cMORF were quantitatively investigated. Because the same pretargeting system was used herein, the following observations from our previous investigations are relevant:…”

Section: Introductionmentioning

confidence: 99%

“…Proof-of concept of MORF pretargeting has been reported [6], the influence of MORF base sequence and chain length has been investigated [7,8], and superior base sequences for this application have been selected [9]. Most recently, the pharmacokinetics of the MORF-MN14 pretargeting age nt and radiolabeled effector were evaluated and an attempt was made to identify the relationship of the effecter accumulation in tumor with the pretargeting variables [10].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice

Liu

Dou

et al. 2006

Eur J Nucl Med Mol Imaging

Self Cite

View full text Add to dashboard Cite

Pretargeting with phosphorodiamidate morpholino oligomers (MORFs) involves a MORFconjugated anti-tumor antibody such as MN14 as pretargeting agent administered before that of the radiolabeled complementary MORF (cMORF) as the effector. The dosages of the pretargeting agent and effector, the pretargeting interval, and the detection time are the four pretargeting variables. The goal of this study was to develop a semiempirical description capable of predicting the biodistribution of the radiolabeled effector in pretargeted mice and then compare predictions with experimental results from pretargeting studies in tumored animals in which the pretargeting interval and the detection time were both fixed but the dosages of both the effector and pretargeting agent were separately varied.Methods-Pretargeting studies in LS174T tumored mice were performed using the anti-CEA antibody MN14 conjugated with MORF and the cMORF radiolabeled with 99m Tc. A description was developed based on our previous observations in the same mouse model of the blood and tumor levels of MORF-MN14, accessibility of MORF-MN14 to labeled cMORF, the tumor accumulation of labeled cMORF relative to MORF-MN14 levels therein, and the kidney accumulation of labeled cMORF. The predicted values were then compared with the experimental values.Results-The predicted biodistribution of the radiolabeled effector and the experimental data were in gratifying agreement in normal organs, suggesting that the description of the pretargeting process was reliable. The tumor accumulations occasionally fell outside two standard deviations of that predicted, but after tumor size correction, good agreement between prediction and experimental values was observed as well.Conclusion-A semiempirical description of the biodistribution of labeled cMORF was capable of predicting the biodistribution of the radiolabeled effector in the pretargeted tumored mouse model, demonstrating that the underlying pretargeting concepts are correct. We believe that the approach described herein may be applied to any of the alternative pretargeting approaches and animal tumor models currently under investigation. Furthermore, appreciation of the concepts may provide a rationale for selecting dosages and timings in human pretargeting studies as an alternative to pure empirical means.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Pretargeting interval-Earlier experience indicated that a pretargeting interval of 2 d was reasonable [10].…”

Section: Timingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice

Liu

Dou

et al. 2006

Eur J Nucl Med Mol Imaging

Self Cite

View full text Add to dashboard Cite

show abstract

DNA‐Targeted Complexes of Tc and Re for Biomedical Applications

Palma,

Santos,

Fernandes

et al. 2024

Chemistry A European J

View full text Add to dashboard Cite

Due to their favorable chemical features, Re and Tc complexes have been widely used for the development of new therapeutic agents and imaging probes to solve problems of biomedical relevance. This review provides an update of the most relevant research efforts towards the development of novel cancer theranostic agents using Re and Tc‐based compounds interacting with specific DNA structures. This includes a variety of homometallic complexes, namely those containing M(CO)3 (M = Re, Tc) moieties, that exhibit different modes of interaction with DNA, such as covalent binding, intercalation, groove binding or G‐quadruplex DNA binding. Additionally, heterometallic complexes, designed to potentiate synergistic effects of different metal centers to improve DNA‐targeting, cytotoxicity and fluorescence properties, are also reviewed. Particular attention is also given to 99mTc‐ and 188Re‐labeled oligonucleotides that have been widely explored to develop imaging and therapeutic radiopharmaceuticals through the in vivo hybridization with a specific complementary DNA or RNA target sequence to provide useful molecular tools in precision medicine for cancer diagnosis and treatment. Finally, the need for further improvement of DNA‐targeted Re and Tc‐based compounds as potential therapeutic and diagnostic agents is highlighted, and future directions are discussed.

show abstract

Use of Morpholino Oligomers for Pretargeting

Liu

2017

Morpholino Oligomers

View full text Add to dashboard Cite

Differing from the conventional direct-targeting strategy in which a probe or payload is directly loaded onto a targeting molecule that binds to the native target, pretargeting is an improved targeting strategy. It converts the native target to an artificial target specific for a secondary targeting molecule loaded with the probe or payload (effector). The effector is small and does not accumulate in normal tissues, which accelerates the targeting process and generates high target to nontarget ratios. DNA/cDNA analogs can serve as the recognition pair, i.e., the artificial target and the secondary targeting effector. Morpholino oligomers are so far the most investigated and the most successful DNA/cDNA analog recognition pairs for pretargeting. Herein, we describe the pretargeting principles, the pretargeting strategy using Morpholino oligomers, and the preclinical success so far achieved.

show abstract

Further investigations of morpholino pretargeting in mice—establishing quantitative relations in tumor

Cited by 29 publications

References 13 publications

Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice

Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice

DNA‐Targeted Complexes of Tc and Re for Biomedical Applications

Use of Morpholino Oligomers for Pretargeting

Contact Info

Product

Resources

About