The performance of a newly developed potential tumor-seeking magnetic resonance (MR) contrast agent ␣-Aqua-13,17-bis(1-carboxypropionyl) carbamoylethyl-3,8-bis(1-phenethyloxyethyl)--hydroxy-2,7,12,18-tetramethyl-porphyrinato manganese (III) (HOP-8P) was tested using a mouse model. Tumorbearing (SCC-VII) mice were imaged using a 1.5T MR imager before and after intravenous administration of 0.1 mmol/kg of HOP-8P. A biodistribution analysis was performed using an optical emission spectrometer. Significant enhancement of the transplanted tumor was observed in MR images 24 h after intravenous injection of HOP-8P. The biodistribution assessment of manganese also correlated with the results of the imaging study. During the 24-h period following contrast administration, HOP-8P was consistently cleared from the circulation, liver, kidneys, and muscle; however, it was progressively accumulated within the tumor. Since precise information about tumor localization and characterization is essential for cancer treatment, there is an ongoing and substantial need for tumor-specific contrast agents. Today, nonspecific extravascular contrast agents such as Gd-DTPA are being used as the workhorse for tumor detection and characterization. Although Gd-DTPA may enhance lesions of high vascularity immediately following intravenous injection, the enhancement is mostly transient, and it immediately leaks into the interstitium. It may also enhance relatively hypovascular fibrous lesion following a time delay, but the degree of enhancement is dependent on the volume of the interstitial space. Therefore, tumor enhancement with gadolinium chelates is fairly nonspecific.Recently, researchers have studied intracellular or cellbound contrast agents to depict hepatocytes (1), Kupffer cells (2), lymph nodes (3), neoplasms (4), and antigens (5). Their research includes the use of porphyrin derivatives for the diagnosis and treatment of malignant tumors. Porphyrins are cyclic tetrapyrrole compounds that are tumor localizers and photosensitizers that are mainly used in photodynamic therapy (6). Since the cyclic tetrapyrrole structure is well suited for metal ion chelation, the compounds have been tested as tumor-seeking MR contrast agents. Following this theme, metalloporphyrins such as manganese tetra (4-sulfonatophenyl) porphyrin was reported to have enhanced human-mouse xenograft models of many neoplasms (7,8).Our agent, ␣-Aqua-13,17-bis(1-carboxypropionyl)carbamoylethyl-3,8-bis(1-phenethyloxyethyl)--hydroxy-2,7,12,18-tetramethyl-porphyrinato manganese (III) (HOP-8P) is a newly developed manganese porphyrin derivative with a side-chain combination that gives the compound amphiphilic characteristics (i.e., hydrophilic and lipophilic at the same time).The purpose of this study was to test the tumor-enhancing characteristics and the biodistribution of this newly developed manganese porphyrin. MATERIALS AND METHODS Contrast MediaThe molecular structure of HOP-8P is illustrated in Fig. 1. The compound is a newly developed manganese porphyrin derivat...
Use of contrast-enhanced multiphase 3D MRA with ultrafast SPGR with shorter TR and TE resulted in clear images of the lateral saccular aneurysm model.
Discriminating between tumours and normal tissues non-invasively is one of the major goals of diagnostic MR imaging. Although tumours are often hypointense on T1-weighted images and hyperintense on T2-weighted images compared to normal tissues even without any contrast media, these findings are not consistently specific. Therefore, a tumour-specific MRI contrast agent remains important for improved detection of tumours, staging, and their characterization. Gadolinium chelates are now being used as the workhorse for detecting tumours in the clinical environment. These contrast media, however, are non-specific extravascular contrast agents. Gadolinium chelates are rapidly delivered to tumours depending on their vascular space, and stay in the tumour depending on the size of the extracellular compartment; however in the majority of the cases, they are rapidly washed out of the tumour. Therefore, the imaging windows for tumour depiction using gadolinium chelates have been quite narrow, and furthermore, the detection of hypovascular tumours has always been problematic with non-specific agents.Porphyrins were the first potentially tissue-specific MR contrast agents to be evaluated because of their ability to form stable chelate complexes with paramagnetic metal ions and their selective retention by tumours. Moreover, complexes containing manganese were identified as potentially the most useful ones because of the high relaxivity of this metal. 2, 4-bis (1-tetrahydro-fulfuroxyethyl)-deuteroporphynyl (IX)-6-7-bisaspartic acid (THF-Mn-ASP), a prototype of HOP-9P, has shown its tumour specific characteristics in a previous report (Suzuki et al, 1996). In this study we perform an initial evaluation of the recently developed HOP-9P as a new tumour seeking MR contrast media using mice in comparison to conventional gadolinium chelates. MATERIALS AND METHODS ChemicalsThe compound, 13, 17-bis (1-carboxypropionyl) carbamoylethyl-3, 8-bis (1-phenylpropyloxyethyl)-2, 7, 12, 18-tetramethyl-porphynato manganese (III) (HOP-9P) has a molecular weight of 1135. In this study, HOP-9P was dissolved with 0.1 M phosphate buffer (pH8.0), and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) (Magnevist, Nihon Schering, Co. Ltd) was diluted with physiological saline before use. Phantom study for relaxivity measurementsThe relaxivity of HOP-9P was measured at 37˚C in 0.9% sodium chloride solution in a 50 ml polypropylene centrifuge tube using a 1.5T super-conductive imager (Magnetom SP, Siemens Medical Systems, Erlangen, Germany). Relaxivity of Gd-DTPA was also measured for comparison. The T1 relaxation times for each solutions were calculated using the spin echo sequence (SE) (TR of 400 and 2400 ms), with 15 ms of TE. A matrix of 256 × 256 and slice thickness of 8 mm were used for the T1 measurements. Summary The purpose of the study is to evaluate the tumour enhancing characteristics and biodistribution of a newly developed metalloporphyrin derivative, HOP-9P (13, 17-bis (1-carboxypropionyl) carbamoylethyl-3, 8-bis (1-phenylpropyloxyeth...
Time-resolved 3D MR angiography can provide high-quality arteriograms. Its performance in revealing renal artery stenosis is comparable with that of conventional angiography.
Dynamic MR dacryocystography, which requires neither ionizing radiation nor chemical contrast media with high viscosity, may be a useful tool for depicting nasolacrimal obstructions.
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