153Sm3+ and 111In3+ DTPA derivatives with high hepatic specificity: in vivo and in vitro studies

Prata, Maria João; Santos, Ana Catarina; Neves, M.; Geraldes, Carlos F. G. C.; Lima, João L. M. P. de

doi:10.1016/s0162-0134(02)00417-8

Cited by 10 publications

(6 citation statements)

References 20 publications

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“…In order to gain further insight into the in vivo behaviour of the trinuclear Gd 3 L, we performed biodistribution and dynamic g scintigraphic studies in Wistar rats using the Sm 3þ analog complex where the gadolinium was replaced by a mixture of radioactive ( 153 Sm) and non-radioactive samarium (22,23). The scintigraphic image obtained 200 s after tracer injection of Sm * 3 L is shown in Fig.…”

Section: Biodistribution and Dynamic Scintigraphic Studiesmentioning

confidence: 99%

In vivo MRI assessment of a novel Gd^III‐based contrast agent designed for high magnetic field applications

Sousa

Livramento

Helm

et al. 2008

Contrast Media & Molecular

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Gd(3)L is a trinuclear Gd(3+) complex of intermediate size, designed for contrast agent applications in high field magnetic resonance imaging (H(12)L is based on a trimethylbenzene core bearing three methylene-diethylenetriamine- N,N,N'',N''-tetraacetate moieties). Thanks to its appropriate size, the presence of two inner sphere water molecules and a fast water exchange, Gd(3)L has remarkable proton relaxivities at high magnetic field (r(1) = 10.2 vs 3.0 mM(-1) s(-1) for GdDOTA at 9.4 T, 37 degrees C, in H(2)O). Here we report an in vivo MRI feasibility study, complemented with dynamic gamma scintigraphic imaging and biodistribution experiments using the (153)Sm-enriched analog. MRI experiments were performed at 9.4 T in mice with Gd(3)L and the commercial contrast agent gadolinium(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (GdDOTA). Gd(3)L was well tolerated by the animals at the dose of 8 micromol Gd kg(-1) body weight. Dynamic contrast enhanced (DCE) images showed considerably higher signal enhancement in the kidney medulla and cortex after Gd(3)L injection than after GdDOTA injection at an identical dose. The relaxation rates, DeltaR(1), were calculated from the IR TrueFISP data. During the excretory phase, the DeltaR(1) for various tissues was similar for Gd(3)L and GdDOTA, when the latter was injected at a three-fold higher dose (24 vs 8 micromol Gd kg(-1) body weight). These results point to an approximately three times higher in vivo relaxivity (per Gd) for Gd(3)L relative to GdDOTA, thus the ratio of the relaxivities of the two compounds determined in vitro is retained under in vivo conditions. They also indicate that the two inner sphere water molecules per Gd in Gd(3)L are not substantially replaced by endogenous anions or other donor groups under physiological conditions. Gd(3)L has a pharmacokinetics typical of small, hydrophilic complexes, involving fast renal clearance and no retention in the blood pool. The dynamic gamma scintigraphic studies and the biodistribution experiments performed in Wistar rats with (153)Sm-enriched (*)Sm(3)L are also indicative of a fast elimination via the kidneys.

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Section: Biodistribution and Dynamic Scintigraphic Studiesmentioning

confidence: 99%

In vivo MRI assessment of a novel Gd^III‐based contrast agent designed for high magnetic field applications

Sousa

Livramento

Helm

et al. 2008

Contrast Media & Molecular

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“…To complement the MRI data, biodistribution and dynamic g scintigraphic studies were performed in Wistar rats using a metallostar solution where the gadolinium was replaced by a mixture of radioactive and non-radioactive samarium (13,14). The scintigraphic image obtained 200 s after tracer injection of 153 Smmetallostar is shown in Fig.…”

Section: Biodistribution and Dynamic Scintigraphic Studiesmentioning

confidence: 99%

Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Livramento

Weidensteiner

Prata

et al. 2006

Contrast Media Mol Imaging

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À ¼ GdDOTA). The metallostar was well tolerated by the animals at the concentrations of 0.0500 (high dose) and 0.0125 (low dose) mmol Gd kg À1 body weight; (BW). The signal enhancement in the inversion recovery fast low angle shot (IR FLASH) images after the high-dose metallostar injection was considerably higher than after GdDOTA injection (0.1 mmol Gd kg À1 BW), despite the higher dose of the latter. The high-dose metallostar injection resulted in a greater drop in the spin-lattice relaxation time (T 1 ), as calculated from the inversion recovery true fast imaging with steady-state precession (IR TrueFISP) data for various tissues, than the GdDOTA or the low dose metallostar injection. In summary, these studies have confirmed that the approximately four times higher relaxivity measured in vitro for the metallostar is retained under in vivo conditions. The pharmacokinetics of the metallostar was found to be similar to that of GdDOTA, involving fast renal clearance, a leakage to the extracellular space in the muscle tissue and no leakage to the brain. As expected on the basis of its moderate molecular weight, the metallostar does not function as a blood pool agent. The dynamic g scintigraphic studies performed in Wistar rats with the metallostar compound having 153 Sm enrichment also proved the renal elimination pathway. The biodistribution experiments are in full accordance with the MR and scintigraphic imaging. At 15 min post-injection the activity is primarily localized in the urine, while at 24 h post-injection almost all radioactivity is cleared from tissues and organs.

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“…cells [2,3]. According to the authors' knowledge, however no attempts have been made to prepare radiolabeled therapeutic 153 Sm-complexes for in vivo studies, except for bone seeking palliative agents such as 153 Sm-EDTMP [4,5] and 153 Sm-PDTMP [6], as well as some radiolabeled antibodies [7] and 153 Sm(III)DTPA for hepatic disease targeting [8]. 153 Sm (T 1/2 = 46.7 h) usually prepared by neutron activation of natural and/or enriched 152 Sm 2 O 3 [9], can be an excellent therapeutic radionuclide, due to its medium energy beta particles for targeted therapy modalities, for developing radiation therapy compounds using small ligands [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…[ 111 In]bleomycin complex has shown high in vitro and in vivo stability and has been successfully used in human tumor detection and therapy [8].…”

Section: Introductionmentioning

confidence: 99%

Biological studies of samarium-153 bleomycin complex in human breast cancer murine xenografts for therapeutic applications

Bahrami-Samani¹,

Ghannadi‐Maragheh²,

Jalilian³

et al. 2010

Radiochimica Acta

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Bleomycin / Sm-153 / Breast cancer-xenograft / Biodistribution / SPECTSummary. In this work, a potential therapeutic DNA targeting agent, 153 Sm-bleomycin complex ( 153 Sm-BLM), was developed and the tumor accumulation studies were performed using single photon emission computed tomography (SPECT) and scarification studies. 153 Sm-BLM was prepared at optimized conditions (room temperature, 4-8 h, 0.1 mg bleomycin for 740-3700 MBq 153 SmCl 3 , radiochemical purity over 98%, HPLC, specific activity = 55 TBq/mmol). 153 Sm-BLM was administered into human breast cancer murine xenografts and the biodistribution and imaging studies were performed up to 48 h. 153 Sm-BLM demonstrated superior tumor accumulation properties in contrast with the other radiolabeled bleomycins with tumor : blood ratios of 41, 72 and 182 at 4, 24 and 48 h, respectively, and tumor : muscle ratios of 23, 33 and > 1490 at 4, 24 and 48 h, respectively, while administered intravenously. The SPECT images also demonstrated the obvious tumor uptake at the chest region of the breast-tumor bearing mice. These initial experiments demonstrate significant accumulation of 153 Sm-BLM in tumor tissues.

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153Sm3+ and 111In3+ DTPA derivatives with high hepatic specificity: in vivo and in vitro studies

Cited by 10 publications

References 20 publications

In vivo MRI assessment of a novel Gd^III‐based contrast agent designed for high magnetic field applications

In vivo MRI assessment of a novel Gd^III‐based contrast agent designed for high magnetic field applications

Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Biological studies of samarium-153 bleomycin complex in human breast cancer murine xenografts for therapeutic applications

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153Sm3+ and 111In3+ DTPA derivatives with high hepatic specificity: in vivo and in vitro studies

Cited by 10 publications

References 20 publications

In vivo MRI assessment of a novel GdIII‐based contrast agent designed for high magnetic field applications

In vivo MRI assessment of a novel GdIII‐based contrast agent designed for high magnetic field applications

Firstin vivo MRI assessment of a self-assembled metallostar compound endowed with a remarkable high field relaxivity

Biological studies of samarium-153 bleomycin complex in human breast cancer murine xenografts for therapeutic applications

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In vivo MRI assessment of a novel Gd^III‐based contrast agent designed for high magnetic field applications

In vivo MRI assessment of a novel Gd^III‐based contrast agent designed for high magnetic field applications