As we continue to cope with the coronavirus disease 2019 pandemic, we can take the opportunity to reflect back and learn from history how unexpected events changed the way we live and work, sometimes in good ways.
On September 11, 2001, many of us were at Rockville, Maryland, attending the HiRes meeting (High Resolution Imaging in Small Animals with PET, MR and Other Modalities: Instrumentation, Applications, and Animal Handling). This conference brought together physicists, biomedical researchers, veterinarians, physicians, and engineers to develop new in vivo imaging tools and methods for biomedical research on small animals. Although the conference was cut short and overshadowed by the tragic event on 9/11, the field of molecular imaging continued to grow and gain recognition for its potential impact on biomedical research (1,2). The driving force behind the growth was several technologic breakthroughs in small-animal imaging, in particular the small-animal PET technology described in the article by Chatziioannou et al. in this anniversary issue of JNM (3).
Initially developed to probe physiologic functions in human and nonhuman primates, PET was not known for its spatial resolution. Several groups attempted to develop high-resolution PET scanners for laboratory animals in the 1990s, with limited success in rodents. Yet, the advances in molecular biology and the availability of transgenic mice called for imaging technologies that could quantify molecular changes in mice noninvasively. The technologic breakthrough came after the group at UCLA adapted a new scintillator: cerium-doped lutetium oxyorthosilicate, leveraging its high light yield to create detectors with high spatial resolution without compromising other performance characteristics (e.g., energy resolution, timing resolution, and scatter fraction). Optical fibers were used to couple scintillation light from lutetium oxyorthosilicate to a position-sensitivity photomultiplier tube to overcome the physical limitations of light sensors at that time. The scanner delivered for the first time an image resolution better than 2 mm in full width at half maximum in all 3 dimensions, a peak system sensitivity of 5.62%, an average energy resolution of 19% in full width at half maximum at 511 keV, and a timing resolution of 2.4 ns in full width at half maximum. Importantly, the system had an excellent linearity and quantitative accuracy between the image value (cps/cm3) and the activity concentration measured by a well counter (MBq/cm3). Representative animal studies demonstrated whole-body PET imaging using FDG and 18F− in rodents, cardiac imaging in a rat, and dynamic imaging of neuroreceptor ligands in a rat. This work marked the beginning of an era during which in vivo quantitative PET imaging of rodents for longitudinal studies become a reality.
After the development of the small-animal PET at UCLA, several seminal works were published demonstrating the potential of molecular imaging for studying biologic processes (2), measuring gene expression in vivo (4), and accelerating drug development (5), among others. The interest in and demand for preclinical PET imaging grew rapidly, leading to the commercialization of small-animal PET technology. The procedures described in the work of Chatziioannou et al. (3) were adapted and became part of the National Electrical Manufacturers Association standard for evaluating the performance of preclinical PET systems. Embraced by many research groups and pharmaceutical companies, in vivo PET imaging became an essential tool to study disease models, to assess novel molecular probes, and to accelerate the screening and validation of targets and drugs using small animals. With additional anatomic or functional images from CT or MRI, preclinical PET/CT and PET/MRI systems are now an integral part of a research pipeline that supports innovation, validation, and translation of novel molecular probes from bench to human for clinical imaging and therapeutic applications.
In 2012, our society changed its name to the Society of Nuclear Medicine and Molecular Imaging, embracing the development of novel molecular probes for preclinical and clinical imaging and therapeutics as our core mission. Although imaging and therapies at the molecular level have always been the backbone of our discipline since its inception 60 years ago, small-animal PET technology likely played a role in accelerating the transformation and reshaping the landscape of our field over the past 2 decades. A recent technologic breakthrough—the total-body PET system (6)—brings immense excitement as we look forward to the new discoveries and clinical applications that will be enabled in the next decade.
As for what happened to the conference after 9/11—with all the airports shut down in North America, many of us took a road trip and drove across the country together to go home. Even in the worst of times, one can find comfort in friends—except that you will need to wear a mask and practice social distancing this time, please!
DISCLOSURE
No potential conflict of interest relevant to this article was reported.
- © 2020 by the Society of Nuclear Medicine and Molecular Imaging.
REFERENCES
- Received for publication June 9, 2020.
- Accepted for publication July 25, 2020.
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