A novel magnetic resonance imaging (MRI) contrast agent containing Herceptin is reported. The surfaces of superparamagnetic iron oxide nanoparticles were modified with dextran and conjugated with Herceptin (Herceptin-nanoparticles) to improve their dispersion, magnetization, and targeting of the specific receptors on cells. From analytical results, we found that Herceptin-nanoparticles were well dispersed in solutions of various pH range, and had no hysteresis, high saturation magnetization (80 emu/g), and low cytotoxicity to a variety of cells. Notably, the magnetic resonance enhancements for the different breast cancer cell lines (BT-474, SKBR-3, MDA-MB-231, and MCF-7) are proportional to the HER2/neu expression level in vitro. When Herceptin-nanoparticles were administered to mice bearing breast tumor allograft by intravenous injection, the tumor site was detected in T (2)-weighted magnetic resonance images as a 45% enhancement drop, indicating a high level of accumulation of the contrast agent within the tumor sites. Therefore, targeting of cancer cells was observed by in vitro and in vivo MRI studies using Herceptin-nanoparticles contrast agent. In addition, Herceptin-nanoparticles enhancing the magnetic resonance signal intensity were sufficient to detect the cell lines with a low level of HER2/neu expression.

A derivative of H 5 ttda ( 3,6,10-tris(carboxymethyl)-3,6,10-triazadodecanedioic acid N-{2-[bis(carboxymethyl)amino]ethyl}-N-{3-[bis(carboxymethyl)amino]propyl}glycine), H 5 [(S)-4-Bz-ttda] ( (4S)-4-benzyl-3,6,10-tris(carboxymethyl)-3,6,10-triazadodecanedioic acid N-{(2S)-2-[bis(carboxymethyl)amino]-3-phenyl-propyl}-N-{3-[bis(carboxymethyl)amino]propyl}glycine; 1) carrying a benzyl group was synthesized and characterized. The stability constants of the complexes formed with Ca 2 , Zn 2 , Cu 2 , and Gd 3 were determined by potentiometric methods at 25.0 AE 0.18 and 0.1m ionic strength in Me 4 NNO 3 . The observed water proton relaxivity value of [Gd{(S)-4-Bz-ttda}] 2À was constant with respect to pH changes over the range pH 4.5 ± 12.0. From the 17 O-NMR chemical shift of H 2 O induced by [Dy{(S)-4-Bz-ttda}] 2À at pH 6.80, the presence of 0.9 inner-sphere water molecules was deduced. The water proton spin-lattice relaxation rate for [Gd{(S)-4-Bz-ttda}] 2À at 37.0 AE 0.18 and 20 MHz was 4.90 AE 0.05 mm À1 s À1 . The EPR transverse electronic relaxation rate and 17 O-NMR transverse-relaxation time for the exchange lifetime of the coordinated H 2 O molecule (t M ), and 2 H-NMR longitudinal-relaxation rate of the deuterated diamagnetic lanthanum complex for the rotational correlation time (t R ) were thoroughly investigated, and the results were compared with those previously reported for the other lanthanide(III) complexes. The exchange lifetime (t M ) for [Gd{(S)-4-Bz-ttda}] 2À (2.3 AE 1.3 ns) was significantly shorter than that of the [Gd(dtpa)(H 2 O)] 2À complex (dtpa diethylenetriaminepentaacetic acid). The rotational correlation time t R for [Gd{(S)-4-Bz-ttda}] 2À (70 AE 6 ps) was slightly longer than that of the [Gd(dtpa)(H 2 O)] 2À complex. The marked increase of relaxivity of [Gd{(S)-4-Bz-ttda}] 2Àmainly resulted from its longer rotational time rather than from its fast water-exchange rate. The noncovalent interaction between human serum albumin (HSA) and the [Gd{(S)-4-Bz-ttda}] 2À complex containing the hydrophobic substituent was investigated by measuring the solvent proton relaxation rate of the aqueous solutions. The association constant (K A ) was less than 100 m À1 , indicating a weaker interaction of [Gd{(S)-4-Bz-ttda}] 2À with HSA.

The Gd(III) complexes of the two dimeric ligands [en(DO3A)2] {N,N'-bis[1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-10-yl-methylcarbonyl]-N,N'-ethylenediamine} and [pi(DTTA)2]8- [bisdiethylenetriaminepentaacetic acid (trans-1,2-cyclohexanediamine)] were synthesized and characterized. The 17O NMR chemical shift of H2O induced by [en{Dy(DO3A)}2] and [pi{Dy(DTTA)}2]2- at pH 6.80 proved the presence of 2.1 and 2.2 inner-sphere water molecules, respectively. Water proton spin-lattice relaxation rates for [en{Gd(DO3A)(H2O)}2] and [pi{Gd(DTTA)(H2O)}2]2- at 37.0 +/- 0.1 degrees C and 20 MHz are 3.60 +/- 0.05 and 5.25 +/- 0.05 mM(-1) s(-1) per Gd, respectively. The EPR transverse electronic relaxation rate and 17O NMR transverse relaxation time for the exchange lifetime of the coordinated H2O molecule and the 2H NMR longitudinal relaxation rate of the deuterated diamagnetic lanthanum complex for the rotational correlation time were thoroughly investigated, and the results were compared with those reported previously for other lanthanide(III) complexes. The exchange lifetimes for [en{Gd(DO3A)(H2O)}2] (769 +/- 10 ns) and [pi{Gd(DTTA)(H2O)}2]2- (910 +/- 10 ns) are significantly higher than those of [Gd(DOTA)(H2O)]- (243 ns) and [Gd(DTPA)(H2O)]2- (303 ns) complexes. The rotational correlation times for [en{Gd(DO3A)(H2O)}2] (150 +/- 11 ps) and [pi{Gd(DTTA)(H2O)}2]2- (130 +/- 12 ps) are slightly greater than those of [Gd(DOTA)(H2O)]- (77 ps) and [Gd(DTPA)(H2O)]2- (58 ps) complexes. The marked increase in relaxivity (r1) of [en{Gd(DO3A)(H2O)}2] and [pi{Gd(DTTA)(H2O)}2]2- result mainly from their longer rotational correlation time and higher molecular weight.

Adenocarcinomas in rats and humans frequently contain perivascular, degranulating mast cells that release heparin. Protamine is a low-molecular weight, cationic polypeptide that binds to heparin and neutralizes its anticoagulant properties. A novel magnetic resonance imaging (MRI) contrast agent containing protamine was synthesized. TTDASQ, the derivative of TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid), was also synthesized and the kinetic stability of [Gd(TTDASQ)]- chelate containing phosphate buffer and ZnCl2 to measure the relaxation rate (R1) at 20 MHz was studied by transmetallation with Zn(II). The water-exchange rate (k(ex)298) of [Gd(TTDASQ)]- is 6.4 x 10(6) s(-1) at 25.0 +/- 0.1 degrees C which was obtained from the reduced 17O relaxation rates (1/T(1r) and 1/T(2r)) and chemical shift (omega(r)) of H(2)17O, and it is compared with that previously reported for the other gadolinium(III) complex, [Gd(DO3ASQ)]. The binding affinity assay showed that the (TTDASQ)3-pro19 has higher activity toward heparin. On the other hand, the effect of heparin on the relaxivity of the [Gd(TTDASQ)3-pro19] conjugate shows the binding strength (K(A)) is 7669 dm3 mol(-1) at pH 7.4 and the relaxivity (r(b)1) of the [Gd(TTDASQ)3-pro19]-heparin adduct is 30.9 dm3 mmol(-1) s(-1).

(1) Background: A variety of stressors may be potentially harmful to adolescents’ health and well-being. Relaxation techniques have been recognized as a valid method for stress release, but the challenge is to apply them practically in schools to produce the desired effects. (2) Methods: This feasibility study used the Perceived Stress Scale (PSS) and hair cortisol concentration (HCC) to test the effects of an abbreviated progressive muscle relaxation (APMR) program on female adolescents. The participants were recruited from a high school and assigned by class cluster to either the experimental group (EG, n = 40) or the control group (CG, n = 35). Both received 4 weeks of stress-related lessons. The EG received 60 additional sessions of APMR over 12 weeks. (3) Results: The program dropout rate of the participants was 1.3%. The EG’s program adhesion rate was 99.1%, and nearly half felt satisfied with the program. After adjusting for the BMI and the pretest in the ANCOVA, it was found that the CG had a greater change in HCC between the pre- and post-tests than the EG, while the PSS did not change significantly in either group. (4) Conclusion: APMR is a valid practice for physiological homeostasis of HCC for female adolescents, but it has no significant effect on perceived stress.

The wa ter 1 H and 17 O NMR re lax ation prop er ties of aque ous so lu tions con tain ing Gd(III) che lates of the DTPA-BIPA, DTPA-BAA, DTPA-BDEA and DTPA-BMA lig ands were in ves ti gated, and the re sults were com pared with those pre vi ously re ported for the Gd(III) com plex with DTPA ligand. The sig nif i cant de vi ation from the monoexponential be hav ior at the es ti ma tion of tem per a ture de pend ence of 1 H lon gi tu di nal relax ation rate for Gd(III) com plexes with DTPA-BIPA, DTPA-BAA and DTPA-BDEA lig ands is char ac ter is tic of the slow chem i cal ex change. The mea sure ments of 17 O NMR trans verse re lax ation rates and EPR transverse elec tronic re lax ation rates in the range 276-343 K, al lowed the as sess ment of the wa ter-exchange lifetime be tween the co or di na tion site and the bulk sol vent. With this ap proach, we ob tained the wa ter-exchange life time ( M ) of 1515, 1429, 1538 and 2128 ns for [Gd(DTPA-BIPA)(, re spec tively. Compared with the M value of 303 ns for [Gd(DTPA)(H2O)] 2-, we are able to con clude that the wa ter res i dence life time in creases when the two termi nal carboxylate groups of DTPA were sub sti tuted by two am ide groups. IN TRO DUC TIONSta bile com plexes of the gad o lin ium(III) ion in aqueous so lu tion are gen er at ing much in ter est as ac tual and po tential con trast agents in bio med i cal mag netic res o nance im aging (MRI).1 Para mag netic metal com plexes are used to increase the im age con trast for MRI. 1,2 The first clin i cally utilized con trast en hance ment agent was [Gd(DTPA)(H 2 O)] 2-, which dis trib utes in the extracellular space and sig nif i cantly in creases pro ton re lax ation rates. Para mag netic metal ions func tion as con trast agents due to the in ter ac tions be tween the elec tron spins of the paramag netic cen ter and the pro ton nu clei, con se quently re sult ing in the in crease of the re lax ation rates for the ob served wa ter pro tons near the ions. For small para mag netic com plexes, wa ter co or di na tion to the metal ion di rectly (in ner sphere) and dif fu sion in the outer sphere en vi ron ment are the two main con tri bu tors to re lax ation en hance ment given by equation (1).(1) R is 1 and R os 1 re fer to the in ner sphere and outer sphere con tri bu tion to the lon gi tu di nal relaxivity, re spec tively. The in ner sphere con tri bu tion for R1 is given by equa tion (2). (2)where M is the con cen tra tion of the metal com plex, q is the num ber of co or di nated in ner sphere wa ter mol e cules, T 1M is the lon gi tu di nal re lax ation time and M is the wa ter res i dence life time on the metal ion. T 1M is a func tion of the in ter ac tion strength and it can be ob tained us ing the Sol o mon-BloembergenMor gan (SBM) the ory, a sim pli fied ver sion is shown in equations (3-4). 1,3 (3) (4) where r is the ef fec tive dis tance be tween the Gd(III) elec tron spin and the wa ter pro tons, H is the pro ton magnetogyric ratio, g is the Landè fac tor, B is the Bohr magneton, S is the spin quan tum ...