1502873-75-7

Upstream product

• 1450624-93-7 N,N′-(2-nitrobenzenesulfonamide)-1-(p-nitrobenzyl)-1,2-diaminoethane 
• 1502873-74-6 N,N′-(2-nitrobenzenesulfonamide)-N,N″-[[6-(methoxycarbonyl)-pyridin-2-yl]methyl]-1-(p-nitrobenzyl)-1,2-diaminoethane 
• 1255535-34-2 2-(p-nitrobenzyl)-(1,2-bis[N,N'-{p-nitrobenzyl}methyl]-N,N'-bis-[6-carboxy-2-pyridylmethyl])ethylenediamine 
• 10294-56-1 phosphorous acid 

Downstream Products

• 1502873-76-8 N,N'-(methylphosphonate)-N,N'-[((6-carboxylato)pyridin-2-yl)methyl]-1-(p-benzyl-isothiocyanato)-1,2-diaminoethane 

Relevant academic research and scientific papers

H6phospa-trastuzumab: Bifunctional methylenephosphonate-based chelator with 89Zr, 111In and 177Lu

The acyclic chelator H6phospa and the bifunctional derivative p-SCN-Bn-H6phospa have been synthesized using nosyl protection chemistry and evaluated with 89Zr, 111In, and 177Lu. The p-SCN-Bn-H6phospa derivative was successfully conjugated to trastuzumab with isotopic dilution assays indicating 3.3 ± 0.1 chelates per antibody and in vitro cellular binding assays indicating an immunoreactivity value of 97.9 ± 2.6%. Radiolabeling of the H 6phospa-trastuzumab immunoconjugate was achieved with 111In in 70-90% yields at room temperature in 30 minutes, while 177Lu under the same conditions produced more inconsistent yields of 40-80%. Stability experiments in human serum revealed the 111In- phospa-trastuzumab complex to be 52.0 ± 5.3% intact after 5 days at 37 °C, while the 177Lu-phospa-trastuzumab to be only 2.0 ± 0.3% intact. Small animal SPECT/CT imaging using mice bearing subcutaneous SKOV-3 ovarian cancer xenografts was performed, and it was found that 111In-phospa-trastuzumab successfully identified and delineated small (～2 mm in diameter) tumors from surrounding tissues, despite visible uptake in the kidneys and bone due to moderate chelate instability. As predicted from stability assays in serum, the 177Lu-phospa-trastuzumab conjugate served as a negative control and displayed no tumor uptake, with high uptake in bones indicating rapid and complete radiometal dissociation and suggesting a potential application of H6phospa in transient lanthanide chelation for bone-delivery. Radiolabeling with 89Zr was attempted, but even with elevated temperatures of 37 °C, the maximum observed radiometal incorporation over 18 hours was 12%. It can be concluded from this work that H6phospa is not superior to the previously studied H 4octapa for use with 111In and 177Lu, but improvements in 89Zr radiolabeling were observed over H 4octapa, suggesting H6phospa to be an excellent starting point for elaboration of 89Zr-based radiopharmaceutical development. To our knowledge, H6phospa is the best desferrioxamine alternative for 89Zr radiolabeling to be studied to date.