dc.contributor.author | Xu, Hong | |
dc.contributor.author | Guo, Hong-fen | |
dc.contributor.author | Lee, Sang-gyu | |
dc.contributor.author | Punzalan, Blesida | |
dc.contributor.author | Chalasani, Sandhya | |
dc.contributor.author | Jungbluth, Achim | |
dc.contributor.author | O’Donoghue, Joseph | |
dc.contributor.author | Cheal, Sarah M. | |
dc.contributor.author | Fung, Edward K. | |
dc.contributor.author | Zanzonico, Pat B. | |
dc.contributor.author | Carrasquillo, Jorge A. | |
dc.contributor.author | Smith-Jones, Peter M. | |
dc.contributor.author | Cheung, Nai-Kong V. | |
dc.contributor.author | Larson, Steven M. | |
dc.contributor.author | Wittrup, Karl Dane | |
dc.date.accessioned | 2016-09-29T17:16:20Z | |
dc.date.available | 2016-09-29T17:16:20Z | |
dc.date.issued | 2015-11 | |
dc.date.submitted | 2015-07 | |
dc.identifier.issn | 1619-7070 | |
dc.identifier.issn | 1619-7089 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/104432 | |
dc.description.abstract | Purpose: GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn–(radiolanthanide metal) complex.
Methods: PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens [superscript 177]Lu-or [superscript 86]Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model.
Results: Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6
(TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq [superscript 177]Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 – 700 mm³) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 – 3.0 based on time to 500-mm³ tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten [superscript 86]Y-DOTA-Bn.
Conclusion: We have developed anti-GPA33 PRIT as a triplestep theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts. | en_US |
dc.description.sponsorship | National Institute of Mental Health (U.S.) (Grant R01-CA-101830) | en_US |
dc.publisher | Springer Berlin Heidelberg | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1007/s00259-015-3254-8 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | Springer Berlin Heidelberg | en_US |
dc.title | Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity [superscript 86]Y- or [superscipt 177]Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates | en_US |
dc.title.alternative | Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity 86Y- or 177Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Cheal, Sarah M. et al. “Theranostic Pretargeted Radioimmunotherapy of Colorectal Cancer Xenografts in Mice Using Picomolar Affinity 86Y- or 177Lu-DOTA-Bn Binding scFv C825/GPA33 IgG Bispecific Immunoconjugates.” European Journal of Nuclear Medicine and Molecular Imaging 43.5 (2016): 925–937. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemical Engineering | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Wittrup, Karl Dane | |
dc.relation.journal | European Journal of Nuclear Medicine and Molecular Imaging | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2016-08-18T15:24:41Z | |
dc.language.rfc3066 | en | |
dc.rights.holder | Springer-Verlag Berlin Heidelberg | |
dspace.orderedauthors | Cheal, Sarah M.; Xu, Hong; Guo, Hong-fen; Lee, Sang-gyu; Punzalan, Blesida; Chalasani, Sandhya; Fung, Edward K.; Jungbluth, Achim; Zanzonico, Pat B.; Carrasquillo, Jorge A.; O’Donoghue, Joseph; Smith-Jones, Peter M.; Wittrup, K. Dane; Cheung, Nai-Kong V.; Larson, Steven M. | en_US |
dspace.embargo.terms | N | en |
mit.license | OPEN_ACCESS_POLICY | en_US |
mit.metadata.status | Complete | |