Metalloporphyrins and Functional Analogues as MRI Contrast Agents

Abstract

Following the footprint of porphyrin-mediated photodynamic therapy (PDT), paramagnetic metalloporphyrins were originated as tumor seeking contrast agents (CAs) for magnetic resonance imaging (MRI). However, serial research has disproved their tumor selectivity, identified nonviable tissues as their real targets, and eventually elicited new applications in myocardial infarction delineation, tissue viability evaluation, ablation therapy assessment, as well as first pass or dynamic perfusion MRI, multi-organ contrast enhancement (CE), atherosclerotic plaque imaging and stem cell labeling or tracking. Furthermore, nonporphyrin analogues have been developed to reduce porphyrin related toxicities. These porphyrin and nonporphyrin compounds have been termed as necrosis-avid contrast agents (NACAs) to denote their major discovered affinity. The present review aims to document the evolving research in this particular field, to discuss possible mechanisms, to promote further preclinical and clinical development of this unique and promising class of MRI CAs, and to implicate a novel stroma targeting strategy for diagnosis and treatment of malignant and benign disorders.

Multiparametric MRI biomarkers for measuring vascular disrupting effect on cancer

“…As an alternative to histopathology, the necrosis ratio from MRI may provide an imaging tool for assessing necrosis for the serial follow-up of patients after reliable necrosis develops. The ultimately reliable determination of necrosis may only be realized with the use of necrosis-avid contrast agents, which are not clinically available [91,92] . Conventional MRI biomarkers are easier to acquire and analyze, while they only reveal incomplete pathophysiological processes, and are often too late compared with Figure 2 In vivo magnetic resonance imaging findings of an implanted tumor in rat liver.…”

Trends in Interdisciplinary Studies Revealing Porphyrinic Compounds Multivalency Towards Biomedical Application

“…Due to cromogenicity, its distribution can also be observed by histology (Chen, 1984;Shahbazi-Gahrouei, 2001). Porphyrin-based complexes were also identified as necrosis-avid contrast agents (NACAs) for noninvasive MRI identification of acute myocardial infarction, assessment of tissue or organ viability, and therapeutic evaluation after interventional therapies (Ni, 2008).…”

MR Contrast Agents for Cardiac Imaging

“…Lack of real tissue and/or disease specificity of these contrast agents have prompted further research and development of more specific MRI contrast agents. One noteworthy issue is that other, more advanced specific or targeting contrast agents always share more or less the nonspecific properties of the ECF contrast agents especially in their early systemic distribution phase, which has been explored for multipurpose applications of certain organ-or tissue-specific contrast agents such as the hepatobiliary Gd-BOPTA (Cavagna et al 1997) and necrosis-avid contrast agents (NACAs) (Ni et al 2002a(Ni et al , b, c, 2005aNi 2008) (Table 1).…”

“…One approach is to synthesize large and median molecules of Gd-containing polymer for prolonged intravascular retention and slower extravasation during renal elimination, as represented by Gd-polylysine (Bogdanov et al 1993), Gadomer-17 (Misselwitz et al 2001) and P792 (Port et al 2001;Taupitz et al 2001), which may feature rapid urinary clearance kinetics. Another approach utilizes the reversible protein-binding property of certain small molecular Gd chelates to form a type of ''semi-endogenous'' BP markers, as represented by gadofosveset trisodium (formerly identified asMS-325 or Angiomark) (Lauffer et al 1998), MP-2269 (Wallace et al 1998) and B-22956 (La Noce et al 2002), as well as other protein-binding (though perhaps somewhat weaker) agents such as Gd-BOPTA (Cavagna et al 1997) and NACAs (Ni 1998;Ni et al 2002a, b, c;Ni et al 2005a;Ni 2008). MS-325 has been the most clinically advanced agent of this class (Lauffer et al 1998).…”