Localization of metalloporphyrin-induced “specific” enhancement in experimental liver tumors: Comparison of magnetic resonance imaging, microangiographic, and histologic findings

Tumor models and specific contrast agents for small animal imaging in oncology

“…It was not until early 1990s that DENA-induced HCC lesions could have been noninvasively characterized by MRI in living rats, on which a methodology paper [6] was granted the Stauffer Award in 1993 by the Association of University Radiologists and Society of Chairs of Academic Radiology Departments [http://www.aur.org/Awards_Training_Grants/stauffer.cfm]. Since then, a research platform based on this model has played a major role in preclinical evaluations of a number of newly developed specific MRI CAs [6,[9][10][11][12][13][14][15] and contributed to the discovery of necrosis avid contrast agents (NACAs) for, among many other applications, determination of myocardial infarction and anticancer therapeutic assessment [16][17][18][19][20].…”

“…High targetability has been desired for development of so called tumor-seeking CAs that preferentially accumulate in the tumor and cause either positive (CR > 1) or negative (CR < 1) tumor CE depending on whether a paramagnetic (row E), or superparamagnetic (row F) agent is applied. Two approaches have been attempted to realize such tumor specificity: (1) using antibodies, of which in vivo applications still remain elusive due to issues such as aggregation, RES clearance and insufficient MRI signal sensitivity; and (2) using porphyrinbased CAs, which is rooted from the porphyrins used in cancer photodynamic therapy (PDT), but has turned out to be a matter of tumor-mistargeting, with the real target having been identified as necrosis or infarction [16][17][18][19][20]. For more comprehensive overviews about advanced oncological imaging techniques and probes in the advocated new era of molecular imaging, readers are recommended to refer to the recent publications [43,44].…”

“…Thanks to the present experimental platform, we have been to identify a new type of tissue specific contrast agents namely necrosis avid contrast agents or NACAs by converting paramagnetic metalloporphyrins from initially intended tumor-seeking CAs into the present in vivo imaging markers for tissue life-status, in addition to other multiple utilities [16][17][18][19][20]. This has led to a number of research extensions: i.e.…”

Efficient and cancer-selective gene transfer to hepatocellular carcinoma in a rat using adenovirus vector with iodized oil esters

“…There are reports that HCC induced by DENA and phenobarbital in rats is hypervascular and is fed by a tumor-specific artery. 19,20 The animal protocol described in this study was approved by the Laboratory Animal Facilities of the Jikei University School of Medicine and performed in accordance with the National Institutes of Health Guidelines.…”

“…This HCC model was selected because its blood supply resembles that of human HCC. 19,20 We then compared the efficiency and cancer selectivity of gene transfer by both methods.…”