Molecular imaging with medical radioisotopes enables the minimally-invasive monitoring of aberrant biochemical, cellular and tissue-level processes in living subjects. The approach requires the administration of radiotracers composed of radioisotopes attached to bioactive molecules, the pairing of which considers several aspects of the radioisotope in addition to the biological behavior of the targeting molecule to which it is attached. With the advent of modern cellular and biochemical techniques, there has been a virtual explosion in potential disease recognition antigens as well as targeting moieties, which has subsequently opened new applications for a host of emerging radioisotopes with well-matched properties. Additionally, the global radioisotope production landscape has changed rapidly, with reactor-based production and its long-defined, large-scale centralized manufacturing and distribution paradigm shifting to include the manufacture and distribution of many radioisotopes via a worldwide fleet of cyclotrons now in operation. Cyclotron-based radioisotope production has become more prevalent given the commercial availability of instruments, coupled with the introduction of new target hardware, process automation and target manufacturing methods. These advances enable sustained, higher-power irradiation of solid targets that allow hospital-based radiopharmacies to produce a suite of radioisotopes that drive research, clinical trials, and ultimately clinical care. Over the years, several different radioisotopes have been investigated and/or selected for radiolabeling due to favorable decay characteristics (i.e. a suitable half-life, high probability of positron decay, etc.), well-elucidated chemistry, and a feasible production framework. However, longer-lived radioisotopes have surged in popularity given recent regulatory approvals and incorporation of radiopharmaceuticals into patient management within the medical community. This review focuses on the applications, nuclear properties, and production and purification methods for some of the most frequently used/emerging positron-emitting, solid-target-produced radioisotopes that can be manufactured using small-to-medium size cyclotrons (≤24 MeV).

We are combining nuclear medicine with molecular biology to establish a sensitive, quantitative, and tomographic method with which to detect gene expression in pancreatic islet cells in vivo. Dual-isotope SPECT can be used to image multiple molecular events simultaneously, and coregistration of SPECT and CT images enables visualization of reporter gene expression in the correct anatomic context. We have engineered pancreatic islet cell lines for imaging with SPECT/CT after transplantation under the kidney capsule. Methods: INS-1 832/13 and αTC1-6 cells were stably transfected with a herpes simplex virus type 1−thymidine kinase−green fluoresecent protein (HSV1-thymidine kinase-GFP) fusion construct (tkgfp). After clonal selection, radiolabel uptake was determined by incubation with 5-¹³¹I-iodo-1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)uracil (¹³¹I-FIAU) (αTC1-6 cells) or ¹²³I-FIAU (INS-1 832/13 cells). For the first set of in vivo experiments, SPECT was conducted after αTC1-6/tkgfp cells had been labeled with either ¹³¹I-FIAU or ¹¹¹In-tropolone and transplanted under the left kidney capsule of CD1 mice. Reconstructed SPECT images were coregistered to CT. In a second study using simultaneous acquisition dual-isotope SPECT, INS-1 832/13 clone 9 cells were labeled with ¹¹¹In-tropolone before transplantation. Mice were then systemically administered ¹²³I-FIAU and data for both ¹³¹I and ¹¹¹In were acquired simultaneously. Results: αTC1-6/tkgfp cells showed a 15-fold greater uptake of ¹³¹I-FIAU, and INS-1/tkgfp cells showed a 12-fold greater uptake of ¹²³I-FIAU, compared with that of wild-type cells. After transplantation under the kidney capsule, both reporter gene expression and location of cells could be visualized in vivo with dual-isotope SPECT. Immunohistochemistry confirmed the presence of glucagon- and insulin-positive cells at the site of transplantation. Conclusion: Dual-isotope SPECT is a promising method to detect gene expression in and location of transplanted pancreatic cells in vivo.

Cardiac magnetic resonance imaging with repeat hypercapnia accurately detects myocardial oxygenation changes in a dog model of ischemic heart disease.

Oxygen-15 (β+, t_1/2 = 122 s) radiolabeled diatomic oxygen, in conjunction with positron emission tomography, is the gold standard to quantitatively measure the metabolic rate of oxygen consumption in the living human brain. We present herein a protocol for safe and effective delivery of [¹⁵O]O₂ over 200 m to a human subject for inhalation. A frugal quality control testing procedure was devised and validated. This protocol can act as a blueprint for other sites seeking to implement similar imaging programs.