Noninvasive assessment of myocardial viability in a small animal model: comparison of MRI, SPECT, and PET.

Acute myocardial infarction (AMI) research relies increasingly on small animal models and noninvasive imaging methods such as MRI, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). However, a direct comparison among these techniques for characterization of perfusion, viability, and infarct size is lacking. Rats were studied within 18-24 hr post AMI by MRI (4.7 T) and subsequently (40-48 hr post AMI) by SPECT ((99)Tc-MIBI) and micro-PET ((18)FDG). A necrosis-specific MRI contrast agent was used to detect AMI, and a fast low angle shot (FLASH) sequence was used to acquire late enhancement and functional images contemporaneously. Infarcted regions showed late enhancement, whereas corresponding radionuclide images had reduced tracer uptake. MRI most accurately depicted AMI, showing the closest correlation and agreement with triphenyl tetrazolium chloride (TTC), followed by SPECT and PET. In some animals a mismatch of reduced uptake in normal myocardium and relatively increased (18)FDG uptake in the infarct border zone precluded conventional quantitative analysis. We performed the first quantitative comparison of MRI, PET, and SPECT for reperfused AMI imaging in a small animal model. MRI was superior to the other modalities, due to its greater spatial resolution and ability to detect necrotic myocardium directly. The observed (18)FDG mismatch likely represents variable metabolic conditions between stunned myocardium in the infarct border zone and normal myocardium and supports the use of a standardized glucose load or glucose clamp technique for PET imaging of reperfused AMI in small animals.

Biodistribution assessment of a lutetium(III) texaphyrin analogue in tumor-bearing mice using NIR Fourier-transform Raman spectroscopy.

The use of near-infrared (NIR)-excited Fourier-transform (FT) Raman spectroscopy as a technique for evaluating the extent of photosensitizer localization in tumor (human pancreatic adenocarcinomas)-bearing mice has been tested using lutetium(III) texaphyrin analogue Lu-T2B2Tex. The complex was injected subcutaneously in the form of three injections given during the course of 3 days. The kinetics of biodistribution were then followed over a time scale of 1-6 days. The NIR-FT-Raman spectra of tissue samples obtained from the xenographic tumor, muscle, heart, brain, liver, spleen, kidney and blood were recorded and used to identify the presence of Lu-T2B2Tex in these tissues. Five Raman sensitizer markers were used to estimate the relative content of Lu-T2B2Tex in tumor at various postinjection times. UV-Visible (Vis) absorption spectroscopic detection of this sensitizer in tissue extracts was applied as a conventional method. Both spectroscopic methods were in good agreement with each other and confirm that Lu-T2B2Tex localizes well in tumor tissue. Maximal drug content was observed 3 days after the final injection. This time delay seems to be optimal for tumor irradiation in photodynamic therapy.

Assessment of a potential tumor-seeking manganese metalloporphyrin contrast agent in a mouse model.

The performance of a newly developed potential tumor-seeking magnetic resonance (MR) contrast agent alpha-Aqua-13,17-bis(1-carboxypropionyl) carbamoylethyl-3,8-bis(1-phenethyloxyethyl)-beta-hydroxy-2,7,12,18-tetramethyl-porphyrinato manganese (III) (HOP-8P) was tested using a mouse model. Tumor-bearing (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. HOP-8P is a promising tumor-seeking metalloporphyrin MR contrast agent with a wide imaging window.