Synthesis and characterization of new porphyrazine-Gd(III) conjugates as multimodal MR contrast agents.
Magnetic resonance imaging (MRI) has long been used clinically and experimentally as a diagnostic tool to obtain three-dimensional, high-resolution images of deep tissues. These images are enhanced by the administration of contrast agents such as paramagnetic Gd(III) complexes. Herein, we describe the preparation of a series of multimodal imaging agents in which paramagnetic Gd(III) complexes are conjugated to a fluorescent tetrapyrrole, namely, a porphyrazine (pz). Zinc metalated pzs conjugated to one, four, or eight paramagnetic Gd(III) complexes are reported. Among these conjugates, Zn-Pz-8Gd(III) exhibits an ionic relaxivity four times that of the monomeric Gd(III) agent, presumably because of increased molecular weight and a molecular relaxivity that is approximately thirty times larger, while retaining the intense electronic absorption and emission of the unmodified pz. Unlike current clinical MR agents, Zn-Pz-1Gd(III) is taken up by cells. This probe demonstrates intracellular fluorescence by confocal microscopy and provides significant contrast enhancement in MR images, as well as marked phototoxicity in assays of cellular viability. These results suggest that pz agents possess a new potential for use in cancer imaging by both MRI and near-infrared (NIR) fluorescence, while acting as a platform for photodynamic therapy.
Department of Chemistry, Northwestern University, Evanston, Illinois, USA.
Ying
Y
Song
Hong
H
Zong
Evan R
ER
Trivedi
Benjamin J
BJ
Vesper
Emily A
EA
Waters
Anthony G M
AG
Barrett
James A
JA
Radosevich
Brian M
BM
Hoffman
Thomas J
TJ
Meade
D000230:Adenocarcinoma / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000532:radiotherapy; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005453:Fluorescence; D005682:Gadolinium / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000532:radiotherapy; D008279:Magnetic Resonance Imaging / Q000379:methods*; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D025202:Molecular Diagnostic Techniques; D008970:Molecular Weight; D010778:Photochemotherapy / Q000379:methods; D011859:Radiography; D045725:Tetrapyrroles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D003287:Contrast Media; D056831:Coordination Complexes; D045725:Tetrapyrroles; D005682:Gadolinium