Limits...
Pretargeted imaging and radioimmunotherapy of cancer using antibodies and bioorthogonal chemistry.

van de Watering FC, Rijpkema M, Robillard M, Oyen WJ, Boerman OC - Front Med (Lausanne) (2014)

Bottom Line: This results in a more rapid clearance of the radioactivity from normal tissues due to the fast pharmacokinetics of the small molecule as compared to antibodies.In the last decade, several pretargeting approaches have been tested, which have shown improved tumor-to-background ratios and thus improved imaging and therapy as compared to directly labeled antibodies.However, to fully integrate the pretargeting approach in clinic, further research should focus on the best regime and pretargeting protocol.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center , Nijmegen , Netherlands.

ABSTRACT
Selective delivery of radionuclides to tumors may be accomplished using a two-step approach, in which in the first step the tumor is pretargeted with an unlabeled antibody construct and in the second step the tumor is targeted with a radiolabeled small molecule. This results in a more rapid clearance of the radioactivity from normal tissues due to the fast pharmacokinetics of the small molecule as compared to antibodies. In the last decade, several pretargeting approaches have been tested, which have shown improved tumor-to-background ratios and thus improved imaging and therapy as compared to directly labeled antibodies. In this review, we will discuss the strategies and applications in (pre-)clinical studies of pretargeting concepts based on the use of bispecific antibodies, which are capable of binding to both a target antigen and a radiolabeled peptide. So far, three generations of the bispecific antibody-based pretargeting approach have been studied. The first clinical studies have shown the feasibility and potential for these pretargeting systems to detect and treat tumor lesions. However, to fully integrate the pretargeting approach in clinic, further research should focus on the best regime and pretargeting protocol. Additionally, recent developments in the use of bioorthogonal chemistry for pretargeting of tumors suggest that this chemical pretargeting approach is an attractive alternative strategy for the detection and treatment of tumor lesions.

No MeSH data available.


Related in: MedlinePlus

PET images of 64Cu-Tz-Bn-NOTA/A33-TCO pretargeting strategy, 64Cu-NOTA-A33 and 89Zr-DFO-A33.Transverse (top) and coronal (bottom) planar images intersect the center of the tumors. This research was originally published in Zeglis et al. (63).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4292049&req=5

Figure 8: PET images of 64Cu-Tz-Bn-NOTA/A33-TCO pretargeting strategy, 64Cu-NOTA-A33 and 89Zr-DFO-A33.Transverse (top) and coronal (bottom) planar images intersect the center of the tumors. This research was originally published in Zeglis et al. (63).

Mentions: Zeglis et al. demonstrated that the in vivo click methodology is able to delineate tumors with PET (62). Nude mice with s.c. SW1222 colorectal cancer xenografts were i.v. administrated with TCO-modified A33 Ab (100 μg) followed 24 h later by 64Cu-NOTA-tetrazine (10.2–12.0 MBq) or with the directly radiolabeled Ab 64Cu-NOTA-A33 (10.2–12 MBq) or 89Zr-DFO-A33 (10.2–12.0 MBq). Despite the higher tumor accumulation of the directly labeled antibodies at 24 h p.i, the pretargeting approach resulted in comparable PET images and tumor-to-muscle ratios (Figure 8).The dose delivered to normal tissues using this pretargeting approach was calculated, indicating that the non-targeted tissues received a significant lower dose when a pretargeting approach (0.0124 mSv/MBq) was used compared to the directly labeled Abs, 64Cu-NOTA-A33, and 89Zr-DFO-A33 (0.0359 and 0.4162 mSv/MBq, respectively).


Pretargeted imaging and radioimmunotherapy of cancer using antibodies and bioorthogonal chemistry.

van de Watering FC, Rijpkema M, Robillard M, Oyen WJ, Boerman OC - Front Med (Lausanne) (2014)

PET images of 64Cu-Tz-Bn-NOTA/A33-TCO pretargeting strategy, 64Cu-NOTA-A33 and 89Zr-DFO-A33.Transverse (top) and coronal (bottom) planar images intersect the center of the tumors. This research was originally published in Zeglis et al. (63).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4292049&req=5

Figure 8: PET images of 64Cu-Tz-Bn-NOTA/A33-TCO pretargeting strategy, 64Cu-NOTA-A33 and 89Zr-DFO-A33.Transverse (top) and coronal (bottom) planar images intersect the center of the tumors. This research was originally published in Zeglis et al. (63).
Mentions: Zeglis et al. demonstrated that the in vivo click methodology is able to delineate tumors with PET (62). Nude mice with s.c. SW1222 colorectal cancer xenografts were i.v. administrated with TCO-modified A33 Ab (100 μg) followed 24 h later by 64Cu-NOTA-tetrazine (10.2–12.0 MBq) or with the directly radiolabeled Ab 64Cu-NOTA-A33 (10.2–12 MBq) or 89Zr-DFO-A33 (10.2–12.0 MBq). Despite the higher tumor accumulation of the directly labeled antibodies at 24 h p.i, the pretargeting approach resulted in comparable PET images and tumor-to-muscle ratios (Figure 8).The dose delivered to normal tissues using this pretargeting approach was calculated, indicating that the non-targeted tissues received a significant lower dose when a pretargeting approach (0.0124 mSv/MBq) was used compared to the directly labeled Abs, 64Cu-NOTA-A33, and 89Zr-DFO-A33 (0.0359 and 0.4162 mSv/MBq, respectively).

Bottom Line: This results in a more rapid clearance of the radioactivity from normal tissues due to the fast pharmacokinetics of the small molecule as compared to antibodies.In the last decade, several pretargeting approaches have been tested, which have shown improved tumor-to-background ratios and thus improved imaging and therapy as compared to directly labeled antibodies.However, to fully integrate the pretargeting approach in clinic, further research should focus on the best regime and pretargeting protocol.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology and Nuclear Medicine, Radboud University Medical Center , Nijmegen , Netherlands.

ABSTRACT
Selective delivery of radionuclides to tumors may be accomplished using a two-step approach, in which in the first step the tumor is pretargeted with an unlabeled antibody construct and in the second step the tumor is targeted with a radiolabeled small molecule. This results in a more rapid clearance of the radioactivity from normal tissues due to the fast pharmacokinetics of the small molecule as compared to antibodies. In the last decade, several pretargeting approaches have been tested, which have shown improved tumor-to-background ratios and thus improved imaging and therapy as compared to directly labeled antibodies. In this review, we will discuss the strategies and applications in (pre-)clinical studies of pretargeting concepts based on the use of bispecific antibodies, which are capable of binding to both a target antigen and a radiolabeled peptide. So far, three generations of the bispecific antibody-based pretargeting approach have been studied. The first clinical studies have shown the feasibility and potential for these pretargeting systems to detect and treat tumor lesions. However, to fully integrate the pretargeting approach in clinic, further research should focus on the best regime and pretargeting protocol. Additionally, recent developments in the use of bioorthogonal chemistry for pretargeting of tumors suggest that this chemical pretargeting approach is an attractive alternative strategy for the detection and treatment of tumor lesions.

No MeSH data available.


Related in: MedlinePlus