RATIONALE AND OBJECTIVES: The authors assess the effect of weak protein binding on the efficacy of gadolinium chelates as contrast agents for magnetic resonance imaging (MRI). METHODS: Chelates with no (gadopentetate dimeglumine), weak (gadobenate dimeglumine), and strong (B-21326/7) protein binding were compared by in vitro MRI at 2T (spin echo [SE]: repetition time [TR]/echo time [TE] 350/8 mseconds) on solutions in 0.5 mM bovine serum albumin and in rat whole blood, and by in vivo MRI at 2T on rat models of brain tumors (SE TR/TE 350/10 mseconds) and of focal blood-brain barrier disruption (SE TR/TE 400/15 mseconds) after injection of MPP+. Relaxation rate enhancement in the blood of normal rabbits was measured in vivo after administration of contrast agents using IR-Snapshot FLASH. RESULTS: Signal intensity enhancement measured in vitro for whole rat blood 0.1 mM in gadobenate was 142% relative to the same concentration of gadopentetate. Peak signal intensity enhancement in brain tumors was 87% +/- 8% and 64% +/- 5% after 0.1 mmol/kg intravenous administration of gadobenate and gadopentetate, respectively; in MPP+ lesions, the peak signal intensity enhancement was 22% +/- 9%, 32% +/- 7%, and 64% +/- 14% after 0.2 mmol/kg intravenous of gadopentetate, gadobenate, and B-21326/7, respectively. In rabbits, the relaxation enhancement of blood 5 minutes after B-21326/7 and gadobenate administration was 323% and 182%, respectively, relative to the same dose (0.1 mmol/kg intravenous) of gadopentetate. CONCLUSIONS: Weak protein binding can substantially increase the efficacy of gadolinium chelates as general purpose contrast agents for MRI.
RATIONALE AND OBJECTIVES: The authors assess the effect of weak protein binding on the efficacy of gadolinium chelates as contrast agents for magnetic resonance imaging (MRI). METHODS: Chelates with no (gadopentetate dimeglumine), weak (gadobenate dimeglumine), and strong (B-21326/7) protein binding were compared by in vitro MRI at 2T (spin echo [SE]: repetition time [TR]/echo time [TE] 350/8 mseconds) on solutions in 0.5 mM bovine serum albumin and in rat whole blood, and by in vivo MRI at 2T on rat models of brain tumors (SE TR/TE 350/10 mseconds) and of focal blood-brain barrier disruption (SE TR/TE 400/15 mseconds) after injection of MPP+. Relaxation rate enhancement in the blood of normal rabbits was measured in vivo after administration of contrast agents using IR-Snapshot FLASH. RESULTS: Signal intensity enhancement measured in vitro for whole rat blood 0.1 mM in gadobenate was 142% relative to the same concentration of gadopentetate. Peak signal intensity enhancement in brain tumors was 87% +/- 8% and 64% +/- 5% after 0.1 mmol/kg intravenous administration of gadobenate and gadopentetate, respectively; in MPP+ lesions, the peak signal intensity enhancement was 22% +/- 9%, 32% +/- 7%, and 64% +/- 14% after 0.2 mmol/kg intravenous of gadopentetate, gadobenate, and B-21326/7, respectively. In rabbits, the relaxation enhancement of blood 5 minutes after B-21326/7 and gadobenate administration was 323% and 182%, respectively, relative to the same dose (0.1 mmol/kg intravenous) of gadopentetate. CONCLUSIONS: Weak protein binding can substantially increase the efficacy of gadolinium chelates as general purpose contrast agents for MRI.
Authors: Maria Antonietta Mazzei; Francesco Gentili; Francesco Giuseppe Mazzei; Paolo Gennaro; Duccio Guerrieri; Andrea Nigri; Guido Gabriele; Elisabetta Weber; Alfonso Fausto; Giuseppe Botta; Luca Volterrani Journal: Radiol Med Date: 2017-08-02 Impact factor: 3.469
Authors: Marie-France Bellin; Judith A W Webb; Aart J Van Der Molen; Henrik S Thomsen; Sameh K Morcos Journal: Eur Radiol Date: 2004-12-31 Impact factor: 5.315
Authors: Chunying Shu; Frank D Corwin; Jianfei Zhang; Zhijian Chen; Jonathan E Reid; Minghao Sun; Wei Xu; Jae Hyun Sim; Chunru Wang; Panos P Fatouros; Alan R Esker; Harry W Gibson; Harry C Dorn Journal: Bioconjug Chem Date: 2009-06 Impact factor: 4.774