Medicine:90Y-DOTA-biotin
90Y-DOTA-biotin consists of a radioactive substance (yttrium-90) complexed by a chelating agent (DOTA), which in turn is attached to the vitamin biotin via a chemical linker. It is used experimentally in pretargeted radioimmunotherapy. Animal studies have been conducted[1][2] as well as clinical studies in humans.[3][4]
In pretargeted radioimmunotherapy, two or three medications are applied in succession. At first, an antibody-drug conjugate is administered, which consists of a monoclonal antibody designed to target the tumour, and a chemical marker which in the case of DOTA-biotin therapy is one of the proteins avidin and streptavidin. After a time of typically one or two days to let the antibody accumulate in the tumour, a clearing agent may be given to eliminate residues of antibody that are still circulating in the bloodstream; this is especially done in humans. After a further waiting time, the radiotherapy (90Y-DOTA-biotin) is administered. Due to the high affinity of biotin to avidin and streptavidin, the radiotherapy accumulates where the antibody is, namely in the tumour, where it delivers its radioactivity.[3]
References
- ↑ Domingo RJ; Reilly RM (2000). "Pre-targeted radioimmunotherapy of human colon cancer xenografts in athymic mice using streptavidin-CC49 monoclonal antibody and 90Y-DOTA-biotin". Nuclear Medicine Communications 21 (1): 89–96. doi:10.1097/00006231-200001000-00015. PMID 10717908.
- ↑ Pagel JM et al. (May 2011). "Anti-CD45 pretargeted radioimmunotherapy using bismuth-213: high rates of complete remission and long-term survival in a mouse myeloid leukemia xenograft model". Blood 118 (3): 703–11. doi:10.1182/blood-2011-04-347039. PMID 21613259.
- ↑ 3.0 3.1 Knox, SJ; Goris, ML; Tempero, M; Weiden, PL; Gentner, L; Breitz, H; Adams, GP; Axworthy, D et al. (2000). "Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU-10 antibody/streptavidin in patients with metastatic colon cancer". Clinical Cancer Research 6 (2): 406–14. PMID 10690517.
- ↑ Paganelli, G.; Ferrari, M.; Ravasi, L.; Cremonesi, M.; De Cicco, C.; Galimberti, V.; Sivolapenko, G.; Luini, A. et al. (2007). "Intraoperative Avidination for Radionuclide Therapy: A Prospective New Development to Accelerate Radiotherapy in Breast Cancer". Clinical Cancer Research 13 (18): 5646s–5651s. doi:10.1158/1078-0432.CCR-07-1058. PMID 17875802.
- ↑ Schultz, Michael K.; Parameswarappa, Sharavathi G.; Pigge, F. Christopher (2010). "Synthesis of a DOTA−Biotin Conjugate for Radionuclide Chelation via Cu-Free Click Chemistry". Organic Letters 12 (10): 2398–401. doi:10.1021/ol100774p. PMID 20423109.
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