Conjugates of vitamin B12 with N ε-functionalized histidine for labeling with [ 99mTc(OH 2) 3(CO) 3] +: synthesis and biodistribution studies in tumor bearing mice

• Published in: Journal of organometallic chemistry Vol. 689; no. 25; pp. 4803 - 4810
• Main Authors: van Staveren, Dave R., Waibel, Robert, Mundwiler, Stefan, Schubiger, P. August, Alberto, Roger
• Format: Journal Article
• Language: English
• Published: LAUSANNE Elsevier B.V 06.12.2004; Elsevier
• Subjects: Biodistribution; Bioorganometallic chemistry; Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Histidine; Physical Sciences; Radiopharmacy; Science & Technology; Technetium; Vitamin B12; BOP; Histidine; EDC; DIPEA; HOBT; TBTU; Bioorganometallic chemistry; Technetium; Radiopharmacy; Vitamin B12; Biodistribution; biodistribution; technetium; RADIOPHARMACEUTICALS; COMPLEXES; CHEMISTRY; vitamin B12; bioorganometallic chemistry; BIOMOLECULES; radiopharmacy; LIGAND; histidine
• ISSN: 0022-328X; 1872-8561
• DOI: 10.1016/j.jorganchem.2004.09.050

Four different cyanocobalamin (vitamin B12) conjugates of histidine are synthesized and subsequently labeled by the reaction with [ 99mTc(OH 2) 3(CO) 3] +. The biodistribution and tumor uptake of the labeled conjugates are determined in mice with B16-F10 melanoma tumors. In this work, histidine derivatives bearing an acetic acid or a propyl amine substituent on the N ε-atom are conjugated to the b-acid, c-acid and d-acid moiety of cyanocobalamin (vitamin B12) via amide formation. Four different derivatives were prepared with different sites of conjugation ( b-, c- or d-acid) and different spacer lengths between histidine and the acid moiety. These conjugates can be efficiently labeled with [ 99mTc(OH 2) 3(CO) 3] + at yields higher than 95% under mild conditions (50 °C, 30 min, 10 −4 M). The biodistribution of the 99mTc(CO) 3 labeled conjugates is determined in mice bearing B16-F10 melanoma tumors. The organ distribution varies significantly for each of the derivatives with the percentage injected dose per gram of tumor tissue ranging from 4.4 ± 0.9 to 9.2 ± 2.0.