A cyclic peptide specific for type I collagen is derivatized with three {Gd(dtpa)} moieties to create a molecular MRI contrast agent for fibrosis imaging. In a mouse model of myocardial infarction (heart attack), collagen levels are elevated in the infarct zone. MRI after injection of the contrast agent selectively enhances and delineates the infarct zone (see preinjection and postinjection images); dtpa=diethylenetriaminepentaacetate.
Ein cyclisches Peptid, das spezifisch für Typ‐I‐Collagen ist, wurde mit drei {Gd(dtpa)}‐Einheiten derivatisiert, um ein molekulares Kontrastmittel für die Kernspintomographie zur Erkennung von Fibrosen zu erzeugen. In einem Mausmodell zum Myokardinfarkt sind die Collagenkonzentrationen in der Infarktzone erhöht. Nach der Injektion des Kontrastmittels ist die Infarktzone deutlicher zu erkennen (siehe Kernspintomogramme); dtpa=Diethylentriaminpentaacetat.
According to this study, the learning curve for LPD consisted of three phases. Conservatively, to attain technical competence for performing LPD, a minimum of 40 cases are required for laparoscopic surgeons with a degree of laparoscopic experience.
MR imaging at high magnetic fields benefits from an increased signal to noise ratio, however T1 based MR contrast agents show decreasing relaxivity (r1) at higher fields. High field, high relaxivity contrast agents can be designed by carefully controlling the rotational dynamics of the molecule. To this end, we investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc protected DOTAla suitable for solid phase peptide synthesis was synthesized and integrated into polypeptide structures. Gd(III) coordination results in very rigid attachment of the metal chelate to the peptide backbone through both the amino acid sidechain and coordination of the amide carbonyl. Linear and cyclic monomers (GdL1, GdC1), dimers (Gd2L2, Gd2C2) and trimers (Gd3L3, Gd3C3) were prepared and relaxivities were determined at different field strengths ranging from 0.47T to 11.7T. Amide carbonyl coordination was indirectly confirmed by determination of the hydration number q for the EuL1 integrated into a peptide backbone, q = 0.96±0.09. The water residency time of GdL1 at 37 °C was optimal for relaxivity, τM=17±2 ns. Increased molecular size leads to increased per Gd relaxivity (from r1 = 7.5 for GdL1 to 12.9 mM−1s−1 for Gd3L3 at 1.4T, 37 °C). The cyclic, multimeric derivatives exhibited slightly higher relaxivities than the corresponding linearized multimers (Gd2C2: r1 = 10.5 mM−1 s−1 versus Gd2C2-red r1 = 9 mM−1s−1 at 1.4T, 37 °C). Overall, all six synthesized Gd complexes had higher relaxivities at low, intermediate and high fields than the clinically used small molecule contrast agent [Gd(HP-DO3A)(H2O)].
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