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90Y-DOTA-biotin

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Y-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 as well as clinical studies in humans.

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 (Y-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.

Example of a Y-DOTA-biotin compound. The structure of the linker, as well as its binding position to DOTA, may vary.

References

  1. 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.
  2. Pagel JM; Kenoyer AL; Bäck T; 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. PMC 3142907. PMID 21613259.
  3. ^ Knox, SJ; Goris, ML; Tempero, M; Weiden, PL; Gentner, L; Breitz, H; Adams, GP; Axworthy, D; Gaffigan, S; Bryan, K; Fisher, DR; Colcher, D; Horak, ID; Weiner, LM (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.
  4. Paganelli, G.; Ferrari, M.; Ravasi, L.; Cremonesi, M.; De Cicco, C.; Galimberti, V.; Sivolapenko, G.; Luini, A.; De Santis, R.; Travaini, L. L.; Fiorenza, M.; Chinol, M.; Papi, S.; Zanna, C.; Carminati, P.; Veronesi, U. (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.
  5. 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. PMC 5506828. PMID 20423109.


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