A New Category of Contrast Media: Water‐soluble Radiopaque Polyvalent Chelates*

Abstract

and the Department of Surgery, Dearborn Veterans Hospital, Dearborn, M k h .The search for ideal contrast media for radiodiagnostic studies has extended over many decades. Although many serviceable contrast media have been developed and are now in clinical use, all the properties of an ideal contrast medium have never been captured in a single preparation. I t is well known that each of the available contrast media has particular, though not necessarily prohibitive, disadvantages. This paper will describe briefly the application of polyvalent-metal chelates as contrast media in bronchography and angiocardiography in anesthetized dogs. Because certain chemical and physical properties are possessed by heavymetal chelates, this group of compounds may be studied profitably for potential use as contrast media. Literally, scores of compounds in this category remain to be synthesized and investigated.Sa~eika,*-~ in 1954, was the first investigator to report the use of polyvalentmetal chelates as contrast media. He used Pb-ethylenediaminetetraacetate (PbEDTA) in a variety of experimental animals and, later, in human beings4 Following this lead, in 1956, Migliorini and Toddei5 in Italy and Shapiro6 in this country published their observations on the use of PbEDTA as a contrast medium in animals. These authors all have been hopefully impressed with this use of this chelate.Chelation has been defined as a reversible reaction between a polyvalent metallic ion and a polyaminocarboxylic acid to form, within the molecule, one or more heterocyclic ring structures, incorporating the metallic ion by both electrovalent and covalent bonds. The metallic ion thus becomes firmly bound and unavailable for chemical or physiological activity. The reaction product is called a chelate, a name derived from the Greek chele, meaning claw, which is descriptive of the "clawlike" structure of the chelate. The physical and chemical properties possessed by some heavy-metal chelates include (1) excellent radiopacity, (2) crystalline structure, ( 3 ) solubility in water, (4) physiological inertness within dosage limits, and (5) rapidity of excretion through the genitourinary tract and, to a lesser degree, the gastrointestinal tract.The literature dealing with the theoretical aspects of chelation chemistry is enormous. However, a brief statement of some pertinent basic concepts will be helpful. The reversible reaction of a chelate and the polyvalent metal is depicted :The equilibrium constant, K , , is a measure of the extent to which chelation

Metal-Based X-ray Contrast Media

“…116 BiDTPA (at a 1.12 M concentration) was evaluated in dogs to explore its potential utility as a bronchography or angiographic agent. 120 It was delivered to the right pulmonary bronchus via catheter for bronchography and was injected iv for angiography. Diagnostically useful bronchograms and angiocardiograms were obtained in both cases.…”

The physical performance of different X-ray contrast agents: calculations using a Monte Carlo model of the imaging chain

“…However, recently (@Hare 1992, Cardinal er d 1993) as well as in earlier work (Oosterkamp 1961, Carlsson 1962, interest has been focused on the possibility of using contrast agents with atomic numbers higher than that of iodine. There has been some effort to develop water soluble contrast media based on cobalt, nickel, copper, zinc, cadmium, lanthanum, cerium, lead and bismuth (Shapiro and Papa 1959, Rubin and Di Chiro 1959, Nalbandian et al 1959, but the toxicity or adverse effects of these media have hitherto been much higher than those of contemporarily developed iodine compounds. The increased attenuation of photons above the K absorption edge of an atom and the increasing energy of this edge with increasing atomic number provide an opportunity to use contrast agents with higher atomic numbers without loss of image quality compared to standard techniques.…”

Visipaque – a Step Forward

“…In spite of the fact that at all photon energies there are several atoms of high mass that are better attenuators of radiation than iodine (Table I), con-trast media based on iodine have been the leading media since the 1920s because they have produced fewer adverse biological effects than their noniodinated competitors. Water-soluble contrast media based on cobalt, nickel, copper, zinc, bromine, strontium, cadmium, lanthanum, cesium, gadolinium, ytterbium, lead and bismuth (22,30,40), have been tried but all have produced adverse effects, that in relation to their efficacy, have hitherto been much more serious than those of contemporary iodinated compounds. The domination of the iodine-based iodinated contrast media has been so large that toxicities of different contrast media have been compared in "iodine equivalent doses" and so far there has been no obvious need for applying the concept of "barn equivalent doses".…”