An N-Acetylgalactosamino Dendron-Clearing Agent for High-Therapeutic-Index DOTA-Hapten Pretargeted Radioimmunotherapy.

Bioconjugate Chemistry
Sarah M ChealSteven M Larson


Clearing agents (CAs) can rapidly remove nonlocalized targeting biomolecules from circulation for hepatic catabolism, thereby enhancing the therapeutic index (TI), especially for blood (marrow), of the subsequently administered radioisotope in any multistep pretargeting strategy. Herein we describe the synthesis and in vivo evaluation of a fully synthetic glycodendrimer-based CA for DOTA-based pretargeted radioimmunotherapy (DOTA-PRIT). The novel dendron-CA consists of a nonradioactive yttrium-DOTA-Bn molecule attached via a linker to a glycodendron displaying 16 terminal α-thio-N-acetylgalactosamine (α-SGalNAc) units (CCA α-16-DOTA-Y3+; molecular weight: 9059 Da). Pretargeting [177Lu]LuDOTA-Bn with CCA α-16-DOTA-Y3+ to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [177Lu]LuDOTA-Bn for blood, tumor, liver, spleen, and kidneys of 11.7, 468, 9.97, 5.49, and 13.3 cGy/MBq, respectively. Tumor-to-normal tissues absorbed-dose ratios (i.e., TIs) ranged from 40 (e.g., for blood and kidney) to about 550 for stomach.


Oct 15, 2009·Molecular Cancer Therapeutics·Michael M Schmidt, K Dane Wittrup
Dec 19, 2009·Protein Engineering, Design & Selection : PEDS·Kelly Davis OrcuttK Dane Wittrup
Mar 5, 2010·International Journal of Radiation Oncology, Biology, Physics·Lawrence B MarksJoseph O Deasy
Jun 10, 2010·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Kelly Davis OrcuttK Dane Wittrup
Sep 8, 2010·Methods in Enzymology·Prabhjit K Grewal
May 23, 2015·Nature Reviews. Cancer·Steven M LarsonOliver W Press
Jul 15, 2017·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Sarah M ChealSteven M Larson

❮ Previous
Next ❯


Sep 23, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brian H SantichNai K Cheung
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Leila Mousavifar, René Roy
Jul 31, 2021·Carbohydrate Research·Anand K AgrahariVinod K Tiwari
Aug 5, 2021·Chemical Society Reviews·Yujun KimInjae Shin
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maryana HandulaYann Seimbille

❮ Previous
Next ❯

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.


Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.


Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
O C BoermanF H Corstens
Ernst Schering Research Foundation Workshop
Giovanni Paganelli
Cancer Biotherapy & Radiopharmaceuticals
A M Wu
European Journal of Nuclear Medicine and Molecular Imaging
Caroline RousseauJean-François Chatal
International Journal of Radiation Oncology, Biology, Physics
R F Meredith, Donald J Buchsbaum
© 2021 Meta ULC. All rights reserved