Greg Freiherr, Industry Consultant

Greg Freiherr has reported on developments in radiology since 1983. He runs the consulting service, The Freiherr Group.

Blog | Greg Freiherr, Industry Consultant | Molecular Imaging | April 13, 2016

Why the Use of PET/CT in Radiation Therapy Requires Thinking Outside the Box

Why the Use of PET/CT in Radiation Therapy Requires Thinking Outside the Box

Graphic courtesy Pixabay

The intersection between PET/CT and radiation therapy is widening. And it is doing so in unanticipated ways.

You might expect this hybrid’s potential against cancer to be found in its natural proclivity for the visualization of malignant tumors, one that has grown more sensitive with the advance of PET technology. Or perhaps you might predict an enhanced ability to see the earliest signs of cancer from the increased sensitivity or localization possible through advances in CT. You might also expect the use of this modality’s unique combination of functional and anatomical data to be leveraged in the planning of therapy, possibly in place or in combination with CT simulators now in use.

But there is where you would be wrong.

Little has come from more than a decade of forward thinking in the latter direction and little is likely to come of it. That does not mean, however, that PET/CT will not have a role to play in the planning of cancer therapy. Far from it.

PET/CT’s biggest opportunity in this regard may stem from the insights this modality can provide about the metabolic pathways of this disease. This potential has been taking shape over the last several years in studies of an enzyme implicated in the occurrence — and treatment — of cancer.

The enzyme, called deoxycytidine kinase, is associated with certain types of cancer. One of the first reports of how PET/CT might use this enzyme to visualize and monitor cancer surfaced about six years ago in the Journal of Nuclear Medicine. The research, conducted in mice, has since been extended to human subjects. Plans for formal clinical trials are now in the works.

The development of a PET agent for this enzyme is still years in the future, as is a commercial radiopharmaceutical that might be widely available. Neither one is a sure thing. But the research may demonstrate how PET/CT could make its long-awaited impact on therapy planning.

In the meantime PET/CT is proving useful as an adjunct to more conventional efforts to visualize and destroy cancer. Recently, the hybrid has been used effectively by research teams in England to identify and guide the removal of cancer cells that remain after the treatment of head and neck cancer. Its use in tracking down elusive malignancies might be leveraged to eliminate the need for patients to undergo invasive post-treatment surgery.

It is encouraging to see such reports, just as it is sobering to realize that PET/CT has not lived up to past expectations, ones that would seem less difficult to achieve.

Peer-reviewed literature abounds with the potential once imagined for PET/CT in radiotherapy planning. Just years after the these two modalities were put together, oncologists and radiation therapists began exploring how the unique combination of structural and functional information might afford better targeting of tumors, according to their distribution, size and metabolic activity.

More than a decade ago the idea appeared of applying these capabilities in the form of a dedicated PET/CT simulator. One paper, published in 2005, concluded that such a simulator could reduce radiation exposure of healthy tissues, thereby intensifying the dose administered to malignancies. Already two years earlier the idea of using PET/CT as a treatment planning tool for conformal radiation therapy had been proven feasible. The paper describing this research, while noting the potential for reduced risk due to minimized dose being applied to healthy tissues, concluded that “the impact on treatment outcome remains to be demonstrated.”

And therein may lay the rub. While the potential of PET/CT and radiation therapy has long been recognized, the challenges standing in the way of its widespread use for the most obvious application in radiation therapy have been formidable. These may be less technological than political and logistical.

First and foremost is the lack of reimbursement for the use of PET/CT in radiotherapy. Second is the fact that PET/CT and radiotherapy planning are done in two different departments — one nuclear medicine; the other radiation therapy. Third is staff training.

While there may be other reasons, these would seem difficult enough. Consequently, realization of PET/CT’s potential in therapy would seem to require thinking outside the simulators — and turf — of radiation therapy planning, as it is practiced today, and more in line with the metabolic pathways that that define the strengths of this hybrid.

Editor’s note: This is the second blog in a series of four by industry consultant Greg Freiherr on Where Molecular Imaging Fits in Managing the Cancer Patient. To read the first blog, “How to Achieve the Quantitative Promise of PET/CT,” click here.

Related Content

Moffitt Cancer Center researchers are developing a noninvasive, accurate method to analyze a patient's tumor mutations and biomarkers to determine the best course of treatment.

Getty Images

News | Lung Imaging | October 19, 2020
October 19, 2020 — Personalized treatment options for patients with...
Indeterminate lesion on PET/CT classified by PET/MRI for 53-y-old man with lung cancer.

Indeterminate lesion on PET/CT classified by PET/MRI for 53-y-old man with lung cancer. Contrast-enhanced CT (A), PET (B), and fused 18F-FDG PET/CT (C) images are displayed in comparison with contrast-enhanced T1-weighted MRI (D), PET, and fused 18F-FDG PET/MRI (F) images. In CT (A), hyperdense, subcentimeter liver lesion (arrows) in segment VII is suggestive of transient hepatic attenuation difference or small hemangioma. As malignancy cannot be excluded, it needs further investigation. On PET/MRI, lesion is clearly classified as metastasis because of contrast enhancement and tracer uptake due to later acquisition time point. Follow-up CT confirmed diagnosis after 78 d. Images created by Ole Martin, University Dusseldorf, Medical Faculty and Benedikt Schaarschmidt, University Hospital Essen.

News | PET-MRI | September 18, 2020
September 18, 2020 — A single-center observational study of more than 1,000 oncological examinations has demonstrated
A 12-year-long collaboration with Canon Medical Research USA, Canon Medical Systems Japan and Southern Nevada outpatient radiology leader Steinberg Diagnostic Medical Imaging (SDMI) has resulted in the development of 3 PET scanners, each generation more advanced than the last
News | PET-CT | September 08, 2020
September 8, 2020 — A 12-year-long collaboration with...
a) Includes scintigraphy and PET with and without concomitant CT. b) Includes conventional radiography, dual-energy x-ray absorptiometry, fluoroscopy, and radiography performed during radiologic interventions. c) Includes general, cardiothoracic, maxillary, plastic, and orthopedic surgery and neurosurgery. d) Includes allergology, cardiology, geriatrics, general internal medicine, pulmonology, gastroenterology, and rheumatology

a) Includes scintigraphy and PET with and without concomitant CT. b) Includes conventional radiography, dual-energy x-ray absorptiometry, fluoroscopy, and radiography performed during radiologic interventions. c) Includes general, cardiothoracic, maxillary, plastic, and orthopedic surgery and neurosurgery. d) Includes allergology, cardiology, geriatrics, general internal medicine, pulmonology, gastroenterology, and rheumatology. Image courtesy of American Roentgen Ray Society (ARRS), American Journal of Roentgenology (AJR)

News | Radiology Imaging | August 14, 2020
August 14, 2020 — According to ARRS' ...
PSMA PET/CT accurately detects recurrent prostate cancer in 67-year-old man. 18F-DCFPyL-PSMA PET/CT shows extensive, intensely PSMA-avid local recurrence in prostate (bottom row; solid arrow) in keeping with the known tumor recurrence in the prostate. Right: PET shows extensive, intensely PSMA-avid local recurrence in prostate (top row; solid arrow) and a solitary bone metastasis in left rib 2 (bottom row; dotted arrow). Image courtesy of Ur Metser, et al.

PSMA PET/CT accurately detects recurrent prostate cancer in 67-year-old man. 18F-DCFPyL-PSMA PET/CT shows extensive, intensely PSMA-avid local recurrence in prostate (bottom row; solid arrow) in keeping with the known tumor recurrence in the prostate. Right: PET shows extensive, intensely PSMA-avid local recurrence in prostate (top row; solid arrow) and a solitary bone metastasis in left rib 2 (bottom row; dotted arrow). Image courtesy of Ur Metser, et al.

News | PET-CT | July 16, 2020
July 16, 2020 — New research confirms the high impact of...
Total-body dynamic 18F-FDG PET imaging with the uEXPLORER scanner allows us to monitor the spatiotemporal distribution of glucose concentration in metastatic tumors in the entire body (a). As compared to a typical clinical standardized uptake value image (b), the parametric image of FDG influx rate (Ki) can achieve higher lesion-to-background (e.g., the liver) contrast. In addition to glucose metabolism imaging by Ki, total-body dynamic PET also enables multiparametric characterization of tumors and organs

Total-body dynamic 18F-FDG PET imaging with the uEXPLORER scanner allows us to monitor the spatiotemporal distribution of glucose concentration in metastatic tumors in the entire body (a). As compared to a typical clinical standardized uptake value image (b), the parametric image of FDG influx rate (Ki) can achieve higher lesion-to-background (e.g., the liver) contrast. In addition to glucose metabolism imaging by Ki, total-body dynamic PET also enables multiparametric characterization of tumors and organs using additional physiologically important parameters, for example, glucose transport rate K1 (d), across the entire body. Image courtesy of G.B. Wang, M. Parikh, L. Nardo, et al., University of California Davis, Calif.

News | PET Imaging | July 16, 2020
July 16, 2020 — Results from the first...
PET/CT imaging showing uptake and retention of 86Y-NM600 (imaging agent) in immunocompetent mice bearing prostate tumors. PET imaging data was employed to estimate tumor dosimetry and prescribe an immunomodulatory 90Y-NM600 (therapy agent) injected activity. Image courtesy of R Hernandez et al., University of Wisconsin-Madison, WI.

PET/CT imaging showing uptake and retention of 86Y-NM600 (imaging agent) in immunocompetent mice bearing prostate tumors. PET imaging data was employed to estimate tumor dosimetry and prescribe an immunomodulatory 90Y-NM600 (therapy agent) injected activity. Image courtesy of R Hernandez et al., University of Wisconsin-Madison, WI.

News | PET-CT | July 15, 2020
July 15, 2020 — ...
Representative maximum-intensity projection PET images of a healthy human volunteer injected with 64Cu-NOTA-EB-RGD at 1, 8, and 24 hours after injection. Axial MRI and PET slices of glioblastoma patient injected with 64Cu-NOTA-EB-RGD at different time points after injection. Image courtesy of Jingjing Zhang et al., Peking Union Medical College Hospital, Beijing, China/ Xiaoyuan Chen et al., Laboratory of Molecular Imaging and Nanomedicine, NIBIB/NIH, Bethesda, USA

Representative maximum-intensity projection PET images of a healthy human volunteer injected with 64Cu-NOTA-EB-RGD at 1, 8, and 24 hours after injection. Axial MRI and PET slices of glioblastoma patient injected with 64Cu-NOTA-EB-RGD at different time points after injection. Image courtesy of Jingjing Zhang et al., Peking Union Medical College Hospital, Beijing, China/ Xiaoyuan Chen et al., Laboratory of Molecular Imaging and Nanomedicine, NIBIB/NIH, Bethesda, USA

News | PET Imaging | July 15, 2020
July 15, 2020 — A first-in-human study presented at the Society of...
Left: Total-body PET/CT in psoriatic arthritis: multiple joints affected, shoulders, elbows, wrists, knees, ankles and small joints of the hands/feet. Arrow: left wrist; arrowhead: right wrist. Middle: Total-body PET/CT in rheumatoid arthritis: multiple joints affected, right shoulder, small joints of the left hand. Arrowhead at the 4th proximal interphalangeal joint shows classic ring-like uptake pattern. Arrow on the foot images demonstrates the hammer toe deformity besides big toe arthritis. Right: Total

Left: Total-body PET/CT in psoriatic arthritis: multiple joints affected, shoulders, elbows, wrists, knees, ankles and small joints of the hands/feet. Arrow: left wrist; arrowhead: right wrist. Middle: Total-body PET/CT in rheumatoid arthritis: multiple joints affected, right shoulder, small joints of the left hand. Arrowhead at the 4th proximal interphalangeal joint shows classic ring-like uptake pattern. Arrow on the foot images demonstrates the hammer toe deformity besides big toe arthritis. Right: Total-body PET/CT in osteoarthritis: affected joints include the left elbow, right knee (arrow) and right big toe (arrowhead). Image courtesy of YG Abdelhafez et al., University of California Davis, Sacramento, CA.

News | SNMMI | July 14, 2020
July 14, 2020 — For the first time, physicians can examine the systemic burden of inflammatory arthritis simultaneous