Metal mediated synthesis of heterocycles and dendrimers.
Synthesis of PAMAM Dendrimer Derivatives with …
Lauterbur, Wiener and Tomalia pioneered the use of dendrimer-based MRI contrast agents by reporting some of the highest known relaxivities for these agents 77, 78. These extraordinary properties have been studied extensively in vivo during the last decade by Kobayashi and Brechbiel. These properties appear to result from a combination of the geometrical amplification of chelated gadolinium that is possible on a dendrimers surface and higher rotational correlation times with minimal segmental motion that are intrinsic to these dendrimer conjugates. Consequently, dendrimer-based Gd(III) chelates consisting of generations 2 and 6 PAMAM dendrimers with 12 and 192 terminal surface amines conjugated to the chelating ligand 2-(4-isothiocyanatobenzyl)-6-methyl diethylene triamine pentaacetic acid through a thiourea linkage were synthesized and used in vivo with rabbits. These contrast agents exhibited excellent MRI images of blood vessels upon intravenous injection. The blood circulation times were sufficiently long, with more than 100 min for large dendrimer conjugates such as the G = 6 PAMAM-TU-Gd(III) - DTPA 79, 80.
Convergent Synthesis of Internally Branched PAMAM Dendrimers
Boron Neutron Capture Therapy: Boron neutron capture therapy is a cancer treatment based on a nuclear capture reaction. When 10B is irradiated with low energy or thermal neutrons, highly energetic a-particles and 7Li ions are produced that are toxic to tumor cells. To achieve the desired effects, it is necessary to deliver 10B to tumor cells at a concentration of at least 109 atoms per cell. One study, involving intratumoral injection of a conjugate between PAMAM dendrimer G5 carrying 1100 boron atoms at its surface and cetuximab, the monoclonal antibody specific for the EGF receptor, showed that the conjugate was present at an almost 10-fold higher concentration in brain tumors than in normal brain tissue 81.