INDICATOR SUBSTANCES AND FLOW ANALYSIS 



621 



commensurately, and there are now textbooks 

 directed to applications of isotopic tracers in biology 

 in general [Kamen (36), Hevesy (33)], and in the 

 specialized fields of biochemistry and physiology 

 [Sacks (54)], agriculture [Comar (16)], and clinical 

 medicine [Veall & Vetter (70), Beierwaltes (4)]. 



Termiriologv 



Some words are used with special meanings in 

 tracer terminology; others are not always used with 

 the same meaning by various authors. The following 

 definitions are taken from an earlier publication (51) 

 in which citations of the original literature providing 

 the basis for the definitions may be foimd. 



A tracer is a labeled form of a substance. Ideally, 

 the label makes the labeled form detectable by the 

 observer without affecting its behavior in the system 

 being studied. In some instances an isotope of one 

 element has been considered as a substitute tracer 

 for a chemically similar element. Substances not 

 normally present in the system being studied, such 

 as colloids and inert gases, may also be treated as 

 tracers. 



The term carrier is used in two senses: /) Unlabeled 

 material of the same or a different ("nonisotopic") 

 element added to a sample containing a tracer as an 

 aid in chemical processing. A logical extension of this 

 meaning includes the unlabeled form of the sub- 

 stance being traced which is normally present in 

 the system. 2) A (usually unknown or postulated) 

 difTerent substance which acts as a transporting 

 vehicle (like a shuttle or ferryboat) in getting the 

 substance being studied through a membrane or 

 across a phase boundary. The sense meant is usually 

 clear from the context. 



The specific activity denotes the ratio of the amount 

 or concentration of the tracer to that of the total 

 (labeled plus unlabeled) substance. Any units which 

 define this ratio may be used. In some applications, 

 microcuries per gram of total substance suffices to 

 denote the specific acti\ity; in other studies the 

 precise location of a tracer element in a labeled 

 molecule must be specified. The term relative specific 

 activity has been used to mean the ratio of the specific 

 activity in one chemical form to that in another. 

 Other authors denote the "fractional amoimt of S 

 (substance) that is tagged" the absolute specific 

 activity, and call the radioactivity per unit amount 

 of 6' the relative specific activity. The latter two terms 

 have the same implications so far as the relative 

 number of isotopic atoms is concerned, and in the 



present discussion specific activity may have either 

 meaning. 



For mathematical purposes the constituents of a 

 living system can be represented as being located in 

 distinguishable phases or volumes designated as pools 

 or compartments. The boundaries of these compartments 

 may, but do not necessarily, conform to anatomical 

 boundaries. For example, the blood plasma is in a 

 relatively easily defined compartment. The location 

 of the bicarbonate pool is more difficult to define 

 but perhaps no less clear in concept, and in some 

 cases a shifting location, such as the cells undergoing 

 mitosis at a given moment, may be regarded as a 

 compartment. 



Transport of a substance into and out of a compart- 

 ment and chemical synthesis and degradation result 

 in appearance and disappearance of the substance 

 in the compartment. The term transfer will denote 

 unidirectional processes of either kind when the 

 mathematics is the same for both kinds. Exchange 

 implies a one-for-one substitution of atoms or mole- 

 cules, or simultaneous and equal transfers into and 

 out of a compartment. The term active transport is 

 used when energy in addition to the diffusion force 

 (i.e., the negative value of the electrochemical po- 

 tential) is involved in effecting transfers. 



In an unconstrained sytem there are direct trans- 

 fers of substance into each compartment from all 

 other compartments in the system. Constrained or 

 restricted exchange systems with the compartments 

 connected chainwise have been designated as catenary 

 (or catenated), or series systems, as contrasted with 

 mammillarv, centrally exchanging or parallel systems 

 which have a single central compartment exchanging 

 with multiple peripheral compartments and with 

 no direct transfers between the peripheral compart- 

 ments. 



The term steady stale is applied to compartments 

 where the rates of removal of the substances being 

 studied are equalled by their rates of replacement, 

 so that the concentrations and amounts of the sub- 

 stances being studied are constant during the period 

 of observation. Constant rates of transfer are also 

 usually specified or implied in mathematical treat- 

 ments but are not required by the definitions of 

 steady state. In particular, the steady state includes 

 situations where different concentrations of an ex- 

 changeable substance are maintained on opposing 

 sides of a membrane and where the difference is 

 greater than can be explained on a simple physical- 

 chemical basis such as a Donnan equilibrium. Of 

 course, during an experiment the tracer itself is 



