Comparison of Pretargeted and Conventional CC49 Radioimmunotherapy Using 149Pm, 166Ho, and 177Lu

Mohsin, Huma; Jia, Fang; Bryan, Jeffrey N.; Sivaguru, Geethapriya; Cutler, Cathy S.; Ketring, Alan R.; Miller, William H.; Simón, Jaime; Frank, R.T.; Theodore, Louis; Axworthy, Donald B.; Jurisson, Silvia S.; Lewis, Michael R.

doi:10.1021/bc200258x

Cited by 24 publications

(20 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the second strategy, antibodies covalently modified with oligomeric nucleic acids are used as the targeting vectors while radiolabeled, complementary oligonucleotide sequences are used as the radioligands (8). Both systems are creative solutions and have proven successful in vivo (9,10). Each, however, possesses significant limitations that threaten their clinical applicability.…”

mentioning

confidence: 99%

A Pretargeted PET Imaging Strategy Based on Bioorthogonal Diels–Alder Click Chemistry

et al. 2013

View full text Add to dashboard Cite

The specificity of antibodies have made immunoconjugates promising vectors for the delivery of radioisotopes to cancer cells; however, their long pharmacologic half-lives necessitate the use of radioisotopes with long physical halsives, a combination that leads to high radiation doses to patients. Therefore, the development of targeting modalities that harness the advantages of antibodies without their pharmacokinetic limitations is desirable. To this end, we report the development of a methodology for pretargeted PET imaging based on the bioorthogonal Diels–Alder click reaction between tetrazine and transcyclooctene. Methods A proof-of-concept system based on the A33 antibody, SW1222 colorectal cancer cells, and 64Cu was used. The huA33 antibody was covalently modified with transcyclooctene, and a NOTA-modified tetrazine was synthesized and radiolabeled with 64Cu. Pretargeted in vivo biodistribution and PET imaging experiments were performed with athymic nude mice bearing A33 antigen–expressing, SW1222 colorectal cancer xenografts. Results The huA33 antibody was modified with transcyclooctene to produce a conjugate with high immunoreactivity, and the 64Cu-NOTA–labeled tetrazine ligand was synthesized with greater than 99% purity and a specific activity of 9–10 MBq/μg. For in vivo experiments, mice bearing SW1222 xenografts were injected with transcyclooctene-modified A33; after allowing 24 h for accumulation of the antibody in the tumor, the mice were injected with 64Cu-NOTA–labeled tetrazine for PET imaging and biodistribution experiments. At 12 h after injection, the retention of uptake in the tumor (4.1 ± 0.3 percent injected dose per gram), coupled with the fecal excretion of excess radioligand, produced images with high tumor-to-background ratios. PET imaging and biodistribution experiments performed using A33 directly labeled with either 64Cu or 89Zr revealed that although absolute tumor uptake was higher with the directly radiolabeled antibodies, the pre-targeted system yielded comparable images and tumor-to-muscle ratios at 12 and 24 h after injection. Further, dosimetry calculations revealed that the 64Cu pretargeting system resulted in only a fraction of the absorbed background dose of A33 directly labeled with 89Zr (0.0124 mSv/MBq vs. 0.4162 mSv/MBq, respectively). Conclusion The high quality of the images produced by this pretargeting approach, combined with the ability of the methodology to dramatically reduce nontarget radiation doses to patients, marks this system as a strong candidate for clinical translation.

show abstract

mentioning

confidence: 99%

A Pretargeted PET Imaging Strategy Based on Bioorthogonal Diels–Alder Click Chemistry

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Clearly a therapeutic reagent which dissipates most of its energy before it reaches its biological target will do more harm than good. For example, Lewis and co-workers 136 reported a comparison of 149 Pm, 166 Ho and 177 Lu for use in CC49 radioimmunotherapy.…”

Section: Future Prospects and Untapped Potentialmentioning

confidence: 99%

Chelating agents for radiolanthanides: Applications to imaging and therapy

Amoroso

Fallis

Pope

2017

Coordination Chemistry Reviews

View full text Add to dashboard Cite

“…[83][84][85][86][87][88][89][90][91][92][93][94][95] These computational models were also integrated in comparative Monte Carlo-based simulations studies investigating patterns of uptake and biodistribution data of radiopharmaceuticals for the purpose of dose estimation in molecular radiotherapy and diagnostic nuclear medical imaging procedures. [96][97][98][99][100][101][102][103][104][105][106][107] For external exposure to ionizing radiation, few studies reported on the calculation of organ dose conversion coefficients for small animals under ideal irradiation conditions (left lateral, right lateral, dorsal-ventral, ventral-dorsal, and isotropic irradiation directions), 26,40 therapeutic irradiation conditions, 23 and diagnostic imaging x-ray irradiations. 60 A number of studies have evaluated factors influencing small animal internal radiation dosimetry.…”

Section: A Ionizing Radiation Dosimetrymentioning

confidence: 99%

Development of computational small animal models and their applications in preclinical imaging and therapy research

Xie

Zaidi

2015

Med. Phys.

View full text Add to dashboard Cite

The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal models have been reported in the literature and used as surrogates to characterize the anatomy of actual animals for the simulation of preclinical studies involving the use of bioluminescence tomography, fluorescence molecular tomography, positron emission tomography, single-photon emission computed tomography, microcomputed tomography, magnetic resonance imaging, and optical imaging. Other applications include electromagnetic field simulation, ionizing and nonionizing radiation dosimetry, and the development and evaluation of new methodologies for multimodality image coregistration, segmentation, and reconstruction of small animal images. This paper provides a comprehensive review of the history and fundamental technologies used for the development of computational small animal models with a particular focus on their application in preclinical imaging as well as nonionizing and ionizing radiation dosimetry calculations. An overview of the overall process involved in the design of these models, including the fundamental elements used for the construction of different types of computational models, the identification of original anatomical data, the simulation tools used for solving various computational problems, and the applications of computational animal models in preclinical research. The authors also analyze the characteristics of categories of computational models (stylized, voxel-based, and boundary representation) and discuss the technical challenges faced at the present time as well as research needs in the future. C 2016 American Association of Physicists in Medicine. [http://dx

show abstract

Comparison of Pretargeted and Conventional CC49 Radioimmunotherapy Using ¹⁴⁹Pm, ¹⁶⁶Ho, and ¹⁷⁷Lu

Cited by 24 publications

References 27 publications

A Pretargeted PET Imaging Strategy Based on Bioorthogonal Diels–Alder Click Chemistry

A Pretargeted PET Imaging Strategy Based on Bioorthogonal Diels–Alder Click Chemistry

Chelating agents for radiolanthanides: Applications to imaging and therapy

Development of computational small animal models and their applications in preclinical imaging and therapy research

Contact Info

Product

Resources

About