An enzyme-activatable and cell-permeable MnIII-porphyrin as a highly efficient T1 MRI contrast agent for cell labeling.

Magnetic resonance imaging (MRI) is a preferred technique for noninvasively monitoring the fate of implanted cells, such as stem cells and immune cells in vivo. Cellular MRI requires contrast agents (CAs) to label the cells of interest. Despite promising progress made in this emerging field, highly sensitive, stable and biocompatible T1 CAs with high cell permeability and specificity remains an unmet challenge. To address this need, a novel MnIII-porphyrin, MnAMP was designed and synthesized based on the modification of MnIIItetra(carboxy-porphyrin) (MnTCP), a small and highly stable non-Gd extracellular CA with good biocompatibility and high T1 relaxivity (r1 = 7.9 mM-1 s-1) at clinical field of 3 Tesla (T). Cell permeability was achieved by masking the polar carboxylates of MnTCP with acetoxymethyl-ester (AM) groups, which are susceptible to hydrolysis by intracellular esterases. The enzymatic cleavage of AM groups led to disaggregation of the hydrophobic MnAMP, releasing activated MnTCP with significant increase in T1 relaxivity. Cell uptake of MnAMP is highly efficient as tested on two non-phagocytic human cell lines with no side effects observed on cell viability. MRI of labeled cells exhibited significant contrast enhancement with a short T1 of 161 ms at 3 T, even though a relatively low concentration of MnAMP and short incubation time was applied for cell labeling. Overall, MnAMP is among the most efficient T1 cell labeling agents developed for cellular MRI.

Gadolinium-free extracellular MR contrast agent for tumor imaging.

PURPOSE: To evaluate a new formulation of manganese porphyrin as a potential gadolinium (Gd)-free extracellular magnetic resonance imaging (MRI) contrast agent for dynamic contrast-enhanced (DCE) MRI of tumors. MATERIALS AND METHODS: A previously reported new contrast agent, MnTCP, was evaluated in six female tumor-bearing nude rats. MRI was performed on a 3 T clinical scanner 3 to 4 weeks after inoculation of breast tumor cells in the mammary fat pads. Gd-DTPA was injected intravenously, followed by injection of MnTCP at least 2 hours later (both at 0.05 mmol/kg). T1 relaxation time measurements and DCE-MRI were performed. RESULTS: Enhancement and clearance patterns were visually similar between MnTCP and Gd-DTPA. However, relative R1 increases in all 11 tumors were larger for MnTCP over 60 minutes postcontrast, the difference being significant as late as 20 minutes (R1post /R1pre = 1.42 ± 0.15 for MnTCP vs. 1.20 ± 0.08 for Gd-DTPA, P < 0.05). R1 -related effects for MnTCP were largely reduced after 60 minutes (R1post /R1pre = 1.13 ± 0.07) and completely gone within 24 hours (R1post /R1pre = 0.97 ± 0.06). DCE-MRI revealed a consistently larger (1.5 to over 2-fold) peak enhancement and higher values of the steepest slope, time-to-peak, and AUC60 in all tumors with MnTCP (P < 0.01). CONCLUSION: MnTCP is an alternative to extracellular Gd agents for tumor imaging, offering sensitive detection and rapid renal clearance.

[Transfer energy disposal in collisions of NaK (6(1)sigma+) with H2].

The radiative lifetimes and rate coefficients for deactivation of high lying 6(1)sigma+ state of NaK by collisions with H2 were studied. An OPO laser was set to a particular 2(1)sigma+ <-- 1(1)sigma+ transition. Another single mode Ti sapphire laser was then used to excite molecule from 2(1)sigma+ level to the 6(1)sigma+ state. The predissociation was monitored by the atomic potassium emission at the 3D --> 4P (1.7 microm) or the S --> 4P (1.24 microm), while bound state radiative processes were monitored by total fluorescence from the upper state to the various levels, all studied as a function of H2 density. The values for predissociation, collisional dissociation and collisional depopulation rate coefficients were obtained. The decay signal of the time resolved fluorescence from the 6(1)sigma+ --> 2(1)sigma+, 6(1)sigma+ -->1(1)sigma+ or 2(1)sigma+ --> 1(1)sigma+ transition was monitored. Based on the Stern-Volmer equation, the radiative lifetimes were monitored for 6(1)sigma+ --> 2(1)sigma+ and 2(1)sigma+ --> 1(1)sigma+ transition. The rate coefficients for deactivation of collisions with H2 were monitored for 6(1)sigma+ --> 2(1)sigma+, 6(1)sigma+ --> 1(1)sigma+ and 2(1)sigma+ -->1(1)sigma+. When the density of H2 was 10(19) cm(-3), the total collisional transfer energy (15 426 cm(-1)) and radiative energy (10 215 cm(-1)) were obtained. The relative fraction ((f(v)), (f(R)), (f(T)) of average energy disposal was derived as (0.58, 0.03, 0.39); (f(v)), (f(R)), (f(T)) represent separately the relative fraction of average energy disposal among vibration, rotation and translation. The major vibrational and translational energy release supports the assumption that the 6(1)sigma(+) -H2 collision occurs primarily in a collisional energy transfer mechanism. In this experiment, alkali molecules relative energy population ratio was determined through using the time integrated intensity, so we can get the total transfer energy. That the NaK (6(1)sigma+) energy transfers to the H2 vibrational, rotational and translational energy was quantitatively given for the first time, which illustrates the collisional mechanism.