The search for new diagnostic approaches is important, especially when they hold promise for solving an unmet clinical need. Yet, no less important is the simplification of methodologic aspects of new techniques. Only then can they be readily, easily, and successfully used in the clinical setting. Taplin and his coworkers had fully recognized such a need for streamlining and simplifying an emerging diagnostic approach by publishing their work, “Suspensions of Radioalbumin Aggregates for Photoscanning the Liver, Spleen, Lung and Other Organs,” in The Journal of Nuclear Medicine in 1964 (1). The nuclear medicine community welcomed Taplin’s contribution, as the high number of citations the article received would suggest, because it set a standard for how to prepare radiolabeled albumin microspheres, how to control their quality and size, how to obtain images of optimum diagnostic quality, and how to avoid possible adverse effects.
Suspensions of sterile and pyrogen-free human serum albumin labeled with 125I or 131I had in fact been in use in clinical investigations and had become commercially available (Albumatope; E.R. Squibb and Sons) (2,3). The emergence of nuclear imaging devices at that time, such as Cassen’s rectilinear scanner or Anger’s γ-camera, accelerated the interest in radioiodinated human serum albumin or albumin derivatives because the 131I label was suitable for radionuclide imaging. Initial studies with human serum albumin aggregates of colloid size had indeed confirmed the feasibility of this radionuclide for imaging (3). The 1964 Taplin publication reads like a cookbook recipe for how to consistently and reproducibly prepare macroaggregates of human serum albumin of different sizes ranging from small-particle colloidal suspensions (10–20 nm) to larger-particle suspensions (1–5 μm). A short section of the article defines physiologic aspects of colloid-sized particles as an underpinning for understanding their pharmacokinetics. After being phagocytosed by Kupffer cells in the liver, macroaggregates are retained in the cells sufficiently long for radionuclide imaging and then are degraded by proteolytic processes, with the radioiodine released into blood in the form of 131I-tyrosine or small proteins or even in free form, with accumulation of 131I in the gastric mucosa as noted on late imaging.
Referring to findings in animals, the text confirms a wide safety margin for albumin aggregates in doses needed for imaging but warns of potentially serious adverse effects from excessive doses of large macroaggregates. Scan doses of the radioligand, even when injected repeatedly, remained without detectable antigenic effects, most likely because human serum albumin had been converted to a particulate form by heat treatment and pH adjustment during its preparation. A series of rectilinear photoscans illustrates the high-quality liver, spleen, and salivary gland images that could be obtained with the new, simplified preparation method. Of note, the series of images includes one of lung perfusion in an experimental animal after intravenous administration of larger (≈15 μm) albumin aggregates. Curiously, a recipe for preparing macroaggregates of the particular size is missing from the paper, even though this size of albumin microspheres became fundamental to imaging of tissue perfusion. Unlike smaller albumin aggregates, they were mechanically trapped in the microvasculature in strict proportion to blood flow. With the observation of microsphere trapping, Taplin laid the foundation for a new imaging approach suitable for studying multiple organs and having a substantial and lasting impact on nuclear medicine imaging, as highlighted by the subsequent pulmonary perfusion imaging for the diagnosis of pulmonary embolism (4).
NOTE
I would like to mention that I had the privilege of personally knowing Dr. George V. Taplin, the author of the publication this commentary addresses. Taplin, or “Tappy,” as we called him, was Professor Emeritus when I joined the Laboratory of Nuclear Medicine and Radiation Biology and the Department of Radiological Sciences at UCLA. In fact, because my office was located next to his, we often talked together or exchanged new ideas. His keen interest in advancing nuclear medicine through high-quality research, and his inquisitive mind, were truly impressive, as was his absolute honesty in judging research accomplishments. Even more so was his encouragement and support of young investigators. Yet, there was never any doubt about Tappy’s pioneering contributions to today’s nuclear medicine.
DISCLOSURE
No potential conflict of interest relevant to this article was reported.
Acknowledgments
I thank Susan Nath for her editorial assistance in preparing this commentary.
- © 2020 by the Society of Nuclear Medicine and Molecular Imaging.
REFERENCES
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- Received for publication May 1, 2020.
- Accepted for publication May 7, 2020.