Relaxometry, animal biodistribution, and magnetic resonance imaging studies of some new gadolinium (III) macrocyclic phosphinate and phosphonate monoester complexes

C. F G C Geraldes, A. D. Sherry, I. Lazar, A. Miseta, P. Bogner, E. Berenyi, B. Sümegi, G. E. Kiefer, K. McMillan, F. Maton, R. N. Muller

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Abstract

The Gd3+ complexes of three new phosphorus containing tetraaza macrocycles (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene ethylphosphonic acid), H4DOTEP; 1,4,7,10-tetraazacyclododecane-1,4,7,10- tetrakis (methylene phosphonic acid monoethylester), H4DOTPME; and the corresponding n-butyl ester, H4DOTPMB) were prepared and examined for possible use as MRI contrast agents. Although thermodynamically and kinetically less stable than Gd(DOTA)- in saline and HSA solution, the stability of these new macrocyclic complexes appears to be sufficiently high for in vivo applications. NMRD relaxivity profiles of the three complexes indicate that the number of inner sphere water molecules for these chelates is ≤1 and that the more hydrophobic chelate, Gd(DOT-PMB), binds to human serum albumin (HSA). Biodistribution studies of the radioactive 153Sm or 159Gd chelates in rats, gamma imaging of the 153Sm chelates in rats, and proton MRI studies of the nonradioactive Gd3+ chelates in rabbits all indicate that the DOTPMB complexes accumulate preferentially in the liver, spleen, and small intestines while the more hydrophilic DOTEP and DOTPME complexes appear to display renal clearances similar to other low molecular weight contrast agents.

Original languageEnglish
Pages (from-to)696-703
Number of pages8
JournalMagnetic Resonance in Medicine
Volume30
Issue number6
DOIs
Publication statusPublished - 1993

Fingerprint

Organophosphonates
Gadolinium
Serum Albumin
Contrast Media
Magnetic Resonance Imaging
Phosphorus
Small Intestine
Protons
Esters
Spleen
Molecular Weight
Rabbits
Kidney
Acids
Water
Liver
1,4,7,10--tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonic acid monoethylester)
gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
1,4,7,10-tetraazacyclododecane--1,4,7,10-tetrakis(methylene ethylphosphonic acid)
cyclen

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Relaxometry, animal biodistribution, and magnetic resonance imaging studies of some new gadolinium (III) macrocyclic phosphinate and phosphonate monoester complexes. / Geraldes, C. F G C; Sherry, A. D.; Lazar, I.; Miseta, A.; Bogner, P.; Berenyi, E.; Sümegi, B.; Kiefer, G. E.; McMillan, K.; Maton, F.; Muller, R. N.

In: Magnetic Resonance in Medicine, Vol. 30, No. 6, 1993, p. 696-703.

Research output: Contribution to journalArticle

Geraldes, C. F G C ; Sherry, A. D. ; Lazar, I. ; Miseta, A. ; Bogner, P. ; Berenyi, E. ; Sümegi, B. ; Kiefer, G. E. ; McMillan, K. ; Maton, F. ; Muller, R. N. / Relaxometry, animal biodistribution, and magnetic resonance imaging studies of some new gadolinium (III) macrocyclic phosphinate and phosphonate monoester complexes. In: Magnetic Resonance in Medicine. 1993 ; Vol. 30, No. 6. pp. 696-703.
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AU - Lazar, I.

AU - Miseta, A.

AU - Bogner, P.

AU - Berenyi, E.

AU - Sümegi, B.

AU - Kiefer, G. E.

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AU - Maton, F.

AU - Muller, R. N.

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