Radiopharmaceutical Development for PET Imaging

PET imaging was initially based on the use of $^{15}O$ labeled to $O_2$, $CO$ and $CO_2$ primarily because the Allis Chalmers cyclotron in use initially at MGH and Washington University was a deuteron machine and was primarily used to producing $^{15}O$. More powerful cyclotrons were available in government laboratories such as Brookhaven but it was not until the mid 70's that such cyclotrons became available to biomedical facilities and the full range of isotopes including $^{11}C$, $^{13}N$,$^{15}O$ and $^{18}F$ became available to a wider audience.

Ter-Pogossian and Powers had demonstrated that $^{15}O$ labeled water could be used to measure blood flow in brain and other organs long before PET was developed (Ter-Pogossian and Powers 1958 [48] and Ter-Pogossian et al 1970 [49]). It should be mentioned that with the untimely death of Michael Ter-Pogossian the field lost a scientist of outstanding ability and integrity.

Oxygen-15 was and remains a very useful label for PET studies and became widely used at MGH for blood flow studies in brain and other organs (Ahluwalia et al 1973 [1], Brownell et al 1976 [14]). The application of labeled $CO_2$ to obtain equilibrium images of blood flow was applied successfully for imaging brain and heart in animals and man (Boucher et al 1976 [3]). The use of labeled $O_2$ together with $CO_2$ provided the basis for measuring regional oxygen metabolism. $^{15}O$ labeled $CO$ provided a means of measuring regional blood volume (Brownell and Cochavi 1978 [15]). Models were developed to obtain quantitative regional values of these important parameters (Subramanyam et al 1978 [46]). The measurement of blood flow and blood volume has become a useful clinical and research tool. By use of these techniques, abnormalities in brain and other organs could be visualized. In addition, alterations in regional cerebral blood flow resulting from visual and other stimuli could be observed (Raichle et al 1973 [42]). More recently magnetic resonance imaging (MRI) has proven capable of observing blood flow and blood volume as well as cerebral metabolism.

It is interesting that one of the factors most responsible for the acceptance of positron imaging was the development of radiopharmaceuticals. In particular, the development of $^{18}F$ labeled 2-fluorodeoxy-D-glucose (2FDG) by the Brookhaven group under the direction of Al Wolf and Joanna Fowler was a major factor in expanding the scope of PET imaging [37]. The half-life of $^{18}F$ was nearly optimal for positron imaging and it was immediately obvious that 2FDG could give precise values of energy metabolism in brain, heart and other organs (Reivich et al 1979 [43]). Michael Phelps further extended the application of 2FDG  [41] based on Sokoloff's autoradiographic studies using $^{14}C$ labeled deoxyglucose (Sokoloff et al 1977 [45]). Recent developments in PET radiopharmaceuticals are based on Henry Wagner's pioneering work on imaging with receptors [51].