Volume 16, Issue 1
The PET Center of Excellence Newsletter is a quarterly member information service published under the direction of the PET CoE leadership and SNMMI
IN THIS ISSUE
PET Center of Excellence
|Katherine Zukotynski, MD, FRCPC
Dear Friends and Colleagues,
When I read PET/CT, I am often amazed by how similar we are anatomically and yet how different we can be in spirit. What is the human spirit, and where is our common ground?
According to Wikipedia, “the human spirit is a component of human philosophy, psychology, art, and knowledge—the spiritual or mental part of humanity.” Where is our common ground? According to the Book of Genesis, it is written that we were once a united people speaking a common language and that we worked together to build a tower that could reach heaven. However, heaven was not ours to reach, and the story of the Tower of Babel ends with a people divided by language and geography across the Earth. Today, it is estimated there are 6,500 languages spoken around the world, some by more than a billion people—others by fewer than 1,000 people. In 1887, Dr. Zamenhof described a language he hoped could unite us and bring international understanding. Esperanto was not widely adopted, and over a century later, we are still searching for a common language and global understanding. Yet, in a way, we may already have our common language. Mathematics, the language of science, can transcend borders. Further, our history is a testament to human perseverance, often despite great hardship. To wit, Joan of Arc, a national symbol of France, overcame great odds to achieve victory for the French in the Hundred Years’ War. Toscanini, an immortal of late 19th and 20th century music, came from a background of poverty. Galileo, a famed mathematician and astronomer, pushed our understanding of the Universe forward despite being persecuted for his findings. Today, PET is at the crossroads of innovation, and the changes that are underway are the foundation of greatness.
Our newsletter includes a lead article on PSMA PET/CT, one of the innovations of present times. Also, there is now CE credit attached to our lead article. We include an article on DOTATATE PET from the technologist perspective as well as cases on pediatric PET/CT and PET/MR. I would like to thank Etienne Rousseau, Marty Schmitt, Helen Nadel, the SNMMI staff and members of the PET CoE and Newsletter Editorial Board who made this publication possible. Further, I would like to congratulate our intern, Shelley Acuff, for winning the 1st place Editor’s Choice Award in 2018 for her paper “Practical Consideration for Integrated PET/CT in Radiation Therapy Planning for Patient Care,” published in JNMT.
We are in the home stretch for the SNMMI Annual Meeting in Anaheim, CA, from June 22-25, and members of the PET CoE have helped organize several educational sessions (listed in this newsletter with rooms and times). In particular, the Peter Valk Memorial Lecture will be given by Dr. Hossein Jadvar and will be followed by the PET CoE Business Meeting on Monday, June 24, from 3-4:30 pm in room 213CD. We hope to see you there!
Finally, looking toward the future, the PET CoE will kick off a webinar series with a talk by Dr. Shana Elman on cardiovascular PET in September, and a PET/MR Workshop will be held October 26-28, 2019, in New York City. Details to follow when available.
Although human history is peppered by tragedy, often born out of prejudice or misunderstanding, it also includes stories of wonder that illustrate the incredible strength of the human spirit. Perhaps most important, past experience teaches that one person can go far, even if alone; however, when we stand united, we can go further, faster. So, let us not forget our common ground!
My presidency has been interwoven with the stuff of dreams, so it seems only fitting that I should pass on the Torch of the PET CoE at Disneyland. No matter how long the road has seemed at times, the views along the way have been beautiful. Thank you to those who have gone before and have made things a little easier. To those who have been my company, I would not be here without you. Finally, to those who will come behind, may the wind be always at your back, and may the road rise up to meet you all the days of your life.
1Département de médecine nucléaire et radiobiologie, Université de Sherbrooke, Sherbrooke (QC), Canada. 2Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Bethesda (MD), United States.
|PLEASE NOTE: This article is available for CE/SAM credit at https://www.snmmilearningcenter.org/Activity/6801385/Detail.aspx—FREE for PET CoE members!|
Prostate Cancer and Nuclear Medicine
Prostate cancer is, without a doubt, a major healthcare concern as it will touch the lives of roughly 11.2% of men and generate considerable costs: a study published in JAMA by Trogdon et al. estimated the 3-year cost to the United States Medicare program for screening for and treating this malignancy in 70+-year-old men to be approximately 1.2 billion dollars. Nuclear medicine has traditionally been involved in its staging/restaging/therapy response assessment with 99mTc-diphosphonate bone scan, but several PET agents are now in clinical use. 18F-FDG, a marker of glucose metabolism, can be used in castration-resistant prostate cancer and can provide prognostic information, but its role remains limited because of low accumulation in most prostate cancer lesions. 18F-NaF, also a bone-seeking agent, has fast plasma clearance and short uptake time—and 18F-NaF PET has higher resolution than bone scintigraphy—but it suffers from the same flaws, that is, the inability to image extraosseous disease and lack of specificity. Choline, present in phospholipids of the cell membrane, can accumulate in prostate cancer because of choline kinase overexpression and be labeled with either 11C (11C-choline) or 18F (18F-fluoromethylcholine, 18F-fluoroethylcholine). It can target soft-tissue lesions, including nodal disease, and has a role in detecting sites of disease in biochemical relapse. 18F-fluciclovine, a radiolabeled synthetic amino acid, has also shown promise for use in biochemical relapse. Its uptake mechanism is based on increased amino acid transporter presence on aggressive neoplastic lesions and, like 11C/18F-choline, it is FDA approved in that setting. All those tracers are nonspecific and can accumulate in a variety of malignancies and benign conditions [1-4].
However, as it turned out, a revolution in prostate cancer imaging that would take the nuclear medicine world by storm was just around the corner.
Prostate-specific membrane antigen (PSMA), a type II membrane protein overexpressed in prostate malignancy, is actually not that new, nor is it specific.
Also known as glutamate carboxypeptidase II, PSMA has been known for quite some time. It was Horoszewicz et al. who researched and developed, in 1983, the LNCaP prostate adenocarcinoma cell line that prompted the creation of a murine monoclonal antibody (7E11-C5) targeting PSMA. 7E11-C5 was then used to create 111In-capromab pendetide, the first PSMA tracer for use in humans, which was approved by the FDA in 1996. While initial results in patients at high risk of disseminated disease were promising, it failed to gain traction in the clinic because of relatively poor sensitivity for disease outside of the prostate gland (10%). This is in part because the antibody targeted the intracellular domain of PSMA, which was essentially only exposed in necrotic cells [5, 6].
Nonetheless, this was not the end of PSMA antibody targeting. In 1997, Liu et al. isolated J591, a new monoclonal antibody that targeted the extracellular domain of PSMA that would be used for patient imaging with greater success than 7E11-C5 with both 111In for scintigraphy/SPECT and 89Zr for PET. Despite progress in targeting PSMA, PET antibody imaging for this malignancy had drawbacks. Like many antibody-based tracers, PSMA-targeting radiolabeled antibodies penetrate tumor tissue poorly, have long blood retention, and have high background signal, thus necessitating delayed imaging with longer-lived isotopes like 89Zr (half-life 3.3 days) that exhibit troublesome dosimetry because of their long half-lives. [7-11].
|Figure 1: 18F-DCFPyL PET/CT MIP image demonstrating tracer biodistribution and a metastatic pelvic lymph node with high PSMA uptake (red arrow). Image courtesy of Dr. François Bénard, BC Cancer (Vancouver, Canada).|
Well on their way to becoming the standard in prostate cancer PET imaging, small molecules based on the glu-urea-lys motif have been gamechangers. Used with PET labels 18F (half-life 110 minutes) and 68Ga (half-life 68 minutes), their favorable pharmacokinetics allowed imaging at early time-points and with better dosimetry. Moreover, uptake in fat, normal lymph nodes, and bone is minimal, which is advantageous since those are frequent sites of metastasis. The number of PSMA-targeting radiopharmaceuticals based on this scaffold ballooned in only a few years, and several PET tracers have been evaluated under clinical research protocols. The better-known are the 68Ga-labeled PSMA-HBED-CC (also known as PSMA-11), PSMA-617, and PSMA I&T as well as the 18F-labeled DCFPyL and PSMA-1007. Biodistribution-wise, these tracers remain very similar, with a few small differences. For instance, PSMA-1007 has particularly low urinary excretion compared with the other tracers, which may be an advantage for evaluation of local recurrence. An example of the biodistribution of this tracer is shown in Figure 1 [6, 9, 11, 12].
There are many reasons why there is such interest in PSMA, especially after development of small-molecule ligands. One is that they have very high uptake in malignant prostatic tissue (100 to 1000 times more cell membrane receptor expression than in normal prostate tissue and other normal organs) with reports that expression increases in castration-resistant phenotypes, with cancer stage, and with tumor grade, allowing for high-contrast imaging. Another is the possibility to leverage that contrast into a high therapeutic index for endoradiotherapy by labeling the ligands that incorporate a compatible chelator with therapeutic isotopes such as 177Lu (half-life 6.7 days; ß- emitter) or 225Ac (half-life 9.9 days; α emitter). Because nearly identical molecules can be leveraged to diagnose and treat prostate cancer, the radioligands are often termed a theranostic pair [11, 13, 14].
As hinted at above, PSMA imaging is actually not that specific for prostate. Small-molecule PSMA-ligands accumulate significantly in kidney cortex, salivary glands, lacrimal glands, liver, spleen, and duodenum. Low uptake may also be seen in sympathetic ganglia (figure 2). Notably, interpreters should be careful to avoid mistaking normal uptake in celiac ganglia for metastatic lymph nodes. Some uptake may also be seen in the nasopharynx and larynx, most likely related to minor salivary and seromucous glands [6, 12, 15].
|Figure 2: 18F-DCFPyL PET (A) and PET/CT fusion image (B) demonstrating uptake in the sympathetic nervous system. Image courtesy of Dr. François Bénard, BC Cancer (Vancouver, Canada).|
With many ongoing large-scale clinical trials across the world, more evidence of PSMA uptake in nonprostate malignancies and benign disease has surfaced. A detailed review article by Sheikhbahaei et al. showed that PSMA tracers accumulate in a variety of other malignancies, for instance (but not limited to): breast cancer, colon cancer, follicular lymphoma, multiple myeloma, papillary/follicular/medullary thyroid cancer, renal cell carcinoma, neuroendocrine tumors, several squamous cell carcinomas, GIST, lung cancer, urothelial cancers, hepatocarcinoma, and salivary gland cancer. Uptake in some of those entities might be related to the PSMA expression in neovasculature [11, 12, 16].
Accumulation has also been reported in many benign conditions such as granulomatous diseases (including sarcoidosis and granulomatosis with polyangiitis), bone conditions (such as Paget’s disease of bone, recent fractures, osseous hemangiomas, fibrous dysplasia), soft-tissue hemangiomas, and neural-origin tumors (e.g., schwannomas, nerve sheath tumors, meningiomas), although many more benign entities with PSMA uptake have been reported [5, 12].
Another important pitfall to keep in mind when interpreting PSMA PET is that not all prostate cancers will show PSMA accumulation. Most notably, some authors have reported that neuroendocrine phenotypes can show little uptake. Review of biopsy or pathology results is thus critical to provide accurate interpretation. Medication has also been reported to affect lesion uptake with PSMA PET. Short-term androgen deprivation therapy has been suggested to increase PSMA expression in prostate cancer metastases, but long-term androgen deprivation therapy may reduce the uptake of castration-sensitive prostate cancer on PSMA PET [17-19].
Despite these apparent shortcomings, because of aforementioned high contrast, PSMA remains clearly useful in restaging after biochemical recurrence. For instance, 68Ga-PSMA-HBED-CC demonstrated detections rates of 57.9% (PSA 0.2 – 0.5 ng/mL), 72.7% (0.5 – 1.0), 93.0% (1.0 – 2.0), and 96.8% (≥ 2.0) and 18F-PSMA-1007 of 61.5%, 74.5%, 90.1%, and 94.1%. Another indicator that PSMA PET has added value compared with other conventional modalities is that 68Ga-PSMA led to a 54% change in management and showed 86% sensitivity and specificity on a per-patient analysis according to a meta-analysis by Han et al. When comparing with 11C/18F-choline and 18F-fluciclovine, 68Ga-PSMA was also shown to have a higher proportion of positive PET/CT scans, according to a review by Evans et al.  Furthermore, due to the high PSMA-ligand uptake demonstrated by tumor tissue, it is possible to detect small nodal metastases that would not otherwise be identified based on size criteria on anatomical imaging like CT, even at sizes that would normally be considered below PET resolution: for detection rates of 50% and 90%, Jilg et al. estimated metastases had to measure ≥ 2.3 mm and ≥ 4.5 mm respectively. An example of PSMA PET uptake in a small node is shown in figure 3 [20-24].
|Figure 3: 18F-DCFPyL PET/CT demonstrating uptake in a small lymph node: (A) Low-dose CT image; (B) Fusion PET/CT image; (C) Zoomed CT. Image courtesy of Dr. François Bénard, BC Cancer (Vancouver, Canada).|
In an interesting twist, the nonspecific uptake of PSMA ligands (for prostate) has actually been leveraged by some to image renal cell carcinoma metastases and salivary cystadenocarcinoma, which then could potentially be targeted for endoradiotherapy by labeling some PSMA ligands with therapeutic radioisotopes like 177Lu or 225Ac. Other cancers that show significant PSMA uptake could potentially be imaged and treated in the same manner [13, 14, 25, 26].
Since the development of the first antibody that targeted the intracellular domain of the prostate-specific membrane antigen, imaging of PSMA has evolved at a tremendous pace. Small-molecule PSMA-targeting radiopharmaceuticals have demonstrated high sensitivity for detection of prostate cancer lesions and also a large impact on management of this malignancy. PSMA PET imaging is not entirely specific, and knowledge of normal biodistribution and frequent pitfalls as well as reader experience are critical for interpretation.
Moreover, ongoing studies of endoradiotherapy using PSMA-targeting ligands have shown promising results. However, as with any new technology, it will take time before we determine the rightful place of PSMA theranostics in our staging and treatment algorithms. One thing is sure, PSMA-based imaging and therapy are here to stay.
1Department of Radiology, British Columbia Children’s Hospital, University of British Columbia, Vancouver, BC, Canada. 2Department of Radiology, Stanford University, Stanford, CA, USA
A 14-year-old girl presented with a two-year history of arm pain and swelling. She was initially imaged with x-ray and CT, which identified lytic and sclerotic cortical defects along the proximal right ulna. The appearance of these findings suggested a non-bacterial chronic osteomyelitis; however, subsequent magnetic resonance (MR) imaging revealed striking soft-tissue abnormalities suggestive of a soft-tissue malignancy. A 99mTc bone scan further demonstrated bony lesions in the proximal right ulna and radius, distal humerus, and the right fourth metacarpal.
A vertex-to-toes, contrast-enhanced 18F-FDG PET/CT scan was then performed for staging and to assess for possible systemic disease (Figure 1A). Multiple sites of abnormal FDG activity were identified in the right forearm, including the known bony lesions around the olecranon, proximal ulna, and radius with a surrounding intensely FDG-avid large tissue mass of more than 11.9 cm. The abnormality in the right fourth metacarpal was also confirmed as having intense FDG avidity. In addition, the scan indicated small-volume lymphadenopathy in the right medial arm, axillary regions bilaterally, the right inguinal area, and iliac regions bilaterally. Further, PET/CT revealed disease in both kidneys, including a large soft-tissue solid mass arising from the lateral aspect of the right kidney that was missed on the prior MRI (Figure 1B). At least two other abnormal FDG-avid soft-tissue densities were seen in both kidneys. Given all of these findings, lymphoma with metastatic bony involvement was the most likely diagnosis. Biopsy confirmed a diagnosis of stage IV B lineage lymphoblastic lymphoma.
A follow-up 18F-FDG PET/CT was performed at the end of the patient’s chemotherapy induction, indicating a complete metabolic response. Unfortunately, three years later, she had recurrence of FDG-avid disease both at the primary site and at multiple distant locations, and she eventually succumbed to her disease.
A 2.5-year-old girl presented with abnormal gait and pain in her left hip. An outside bone scan revealed osseous abnormalities in the right femur, proximal left tibia, and scattered ribs, with a suspected diagnosis of lymphoma. Subsequently, a contrast-enhanced 18F-FDG PET/CT was performed from vertex to toes to further assess the disease. On PET/CT, osseous abnormalities were shown to be more extensive than on the bone scan (Figure 2A). Most strikingly, the PET/CT revealed a large FDG-avid soft-tissue mass arising from and focally obliterating the right calvarial frontal bone, which was previously unknown (Figure 2B). In hindsight, some unusual mild inhomogeneity of tracer activity was visualized on the right side of the skull on the previous bone scan, but this lesion was much more apparent on PET/CT. The soft tissue mass extended both intra- and extra-cranially, with marked compression of the frontal lobe and ventricles. Permeative bone destruction was present within much of the skull base and calvarium bilaterally. Further hypermetabolic bony lesions were identified throughout the mandibular angles, proximal humeri, scapulae, sternum, ribs, iliac wings, acetabulae, femora, and tibiae. Cervical and supraclavicular lymphadenopathy also was identified. PET/CT also revealed splenic and hepatic involvement. Biopsy confirmed stage IV diffuse large B-cell lymphoma.
Follow-up 18F-FDG PET/CT scans performed after two cycles of chemotherapy and at the end of treatment showed complete metabolic resolution. One year later, the patient presented again with a 1-week history of decreased energy and appetite. Subsequent investigations and 18F-FDG PET/CT scans indicated relapse of disease, with diffuse abnormal lytic bony disease throughout the entire skeleton, in keeping with a diagnosis of acute lymphoblastic leukemia. The patient unfortunately eventually succumbed to her disease.
Lymphoma is one of the most common pediatric cancers, with non-Hodgkin lymphomas (NHL) making up about two-thirds of pediatric lymphomas . The 3 most common NHL diagnoses include Burkitt lymphoma (40% of pediatric NHL), lymphoblastic lymphoma (30%, usually of T-cell lineage), and diffuse large B-cell lymphoma (25%) . The overall long-term survival rate for each of these lymphomas in children after 5 years is 80-90% [3,4]
In both of these cases, 18F-FDG PET/CT was able to detect systemic disease previously unidentified on prior scans and improve the accuracy of disease staging for these patients. As shown by these cases, 18F-FDG PET/CT is highly effective in assessing the full extent of systemic disease in pediatric NHL, therefore providing a more accurate view of a patient’s disease both at baseline and on follow-up. 18F-FDG PET/CT was also able to preliminarily distinguish between lymphoma and sarcoma prior to biopsy based on imaging findings.
Rather unusually, both of these patients also had disease outside of the typical eyes-to-thighs. While the disease in the upper extremity in case A was already known, the brain lesion in case B was not previously identified and therefore impacted patient management. A recent study of pediatric lymphoma in 11 centers worldwide found that identification of lesions outside of the eyes-to-thighs region had essentially no impact on clinical stage or treatment . Case B, however, indicates a case where early identification of a brain lesion by PET/CT was crucial in the patient’s treatment definition. While true whole-body scans may not be necessary in most cases, there is still a small fraction of cases where unexpected findings outside of the eyes-to-thighs area can be identified by 18F-FDG PET/CT. Such findings can potentially offer the benefit of improved understanding of a patient’s disease, overall patient management, and clinical outcome.
1Department of Radiology, British Columbia Children’s Hospital, University of British Columbia, Vancouver, BC, Canada. 2Department of Radiology, Stanford University, Stanford, CA
A previously healthy 17-year-old female presented with a two-week history of cough and congestion and painful right-sided cervical lymphadenopathy. She was initially diagnosed with sinusitis and thought to have reactive lymphadenopathy. Two months later, she presented again with persistent lymphadenopathy, drenching night sweats, and ongoing, though improving, cough. A chest x-ray revealed a mediastinal and left hilar mass, which was confirmed on CT. Ultrasound further revealed lower neck and supraclavicular lymphadenopathy. Fine needle aspiration and cervical core biopsy was consistent with classical Hodgkin lymphoma with CD30+ and Reed-Sternberg cells.
18F-FDG PET/MR was performed to stage the disease. Multiplanar, multisequence MRI was performed from vertex to toes, with intravenous gadolinium-containing contrast. PET/MR was able to characterize the intensely FDG-avid right cervical chain conglomerate lymphadenopathy as well as several smaller hypermetabolic left-sided cervical nodes (Figure 1A). Bilateral symmetrical brown fat was also identified. The extent of the bilateral supraclavicular, mediastinal, and hilar lymphadenopathy was also evaluated (Figure 1B). PET/MR also demonstrated further lymphadenopathy below the diaphragm, with extensive hypermetabolic lymph nodes in the iliac chains bilaterally and in the right periaortic chain (Figure 1C). These lesions were well-characterized and anatomically correlated using the post gadolinium contrast T1 images on MRI (Figure 1B-C). Additional focal lesions were also seen in the spleen, bilateral iliac bones, sacroiliac regions, and sacrum. This extensive, multistation lymphadenopathy both above and below the diaphragm was consistent with stage IVB Hodgkin disease.
The patient was started on OEPA-COPDAC chemotherapy, and a follow-up PET/MR was performed to assess response to treatment following the second cycle. Findings showed excellent treatment response, with interval decrease in size and FDG-avidity or metabolic resolution of numerous lymph nodes in the neck, chest, and pelvis and complete or near-complete metabolic resolution of osseous lesions in the axial skeleton. Overall, this study indicated a Deauville score of 3, consistent with a near-complete metabolic response.
About one-third of pediatric lymphoma is classified as Hodgkin lymphoma . This type of lymphoma is characterized by the presence of Reed-Sternberg cells, which have distinct large cell morphology . Hodgkin lymphoma has an incident rate of around three cases per 100,000 individuals, is most prevalent in young adults, and has a relatively high cure rate . However, a recent study found a high incidence of radiation-associated secondary malignancies in patients with a history of Hodgkin lymphoma . For this reason, reduction of radiation to the patient wherever possible may aid in mitigating this risk.
Currently, 18F-FDG PET/CT is widely used to assess pediatric Hodgkin lymphoma and other cancers . However, compared to PET/CT, 18F-FDG PET/MR has the advantage of a lower radiation dose, while maintaining an equivalent lesion detection rate, and can also reduce the number of scans a patient requires by removing the need for an additional MR scan [4,5]. The main disadvantage of using PET/MR is that scanning time tends to be significantly longer than PET/CT [4,5]. Therefore, PET/MR may be particularly useful in children with systemic disease, such as in this case.
In this case, PET/MR was able to successfully stage and assess response to treatment in pediatric Hodgkin lymphoma. The initial vertex-to-toes scan was able to characterize the full extent of disease and accurately stage the disease. In particular, previously unknown lymphadenopathy and bony metastases below the diaphragm were revealed on the staging PET/MR. The complete resolution of most of these lesions was seen on the follow-up scan, which indicated the effectiveness of the current treatment. 18F-FDG PET/MR was overall highly valuable in staging disease, assessing response to treatment, and aiding decision-making around patient management and further treatment. This imaging modality may thus be useful in evaluating future cases of pediatric Hodgkin lymphoma, with the benefit of relatively low radiation exposure.
The introduction of Netspot (68Ga-DOTATATE kit; Advanced Accelerator Applications), a new PET diagnostic imaging agent and procedure, has improved our physicians’ ability to manage patients with neuroendocrine tumors (NETs), as compared to traditional nuclear medicine imaging with Octreoscan (111In-pentetreotide). Introducing a new procedure can be daunting for any department, especially if only one imaging agent has predominantly been used. We hope this review of our experience implementing Netspot into a busy and diverse department will prove valuable to the reader.
Netspot and Octreoscan both are localized in tumors with somatostatin receptors. The primary difference between them is the isotope used to label the somatostatin analog: a 68Ga positron emitter versus 111In. Positron emitters have certain advantages for PET imaging, including a higher energy photon (511 keV for 68Ga as compared to the 171 and 245 keV photopeaks of 111In), superior resolution, increased counting statistics, and attenuation correction. Additionally, PET provides the ability for quantification via standardized uptake values (SUVs), which is advantageous for repeat examinations during treatment monitoring.
Prior to implementing Netspot imaging in your facility, you should consider several factors. Most important: availability of the drug. 68Ga is a generator-produced radioisotope, so it has inherent limitations. Netspot is available as a reaction vial with lyophilized powder and must be radiolabeled with 68Ga through a licensed radiopharmacy. Questions such as these must be addressed: Where is the closest radiopharmacy? How many 68Ga generators does it have? How many hospitals is it currently supplying with the drug? Because the amount of radioactivity obtained per elution and the number of elutions per day are limited, the pharmacy may not be able to accommodate adding more doses to their daily schedule. The radiopharmacy is limited by the amount of radioactivity that can be obtained from each elution and the number of elutions that can be made. The distance and travel time from the radiopharmacy must also be considered, since the half-life of 68Ga is 68 minutes.
As you set up your facility, the next significant consideration relates to the scanner you intend to use for Netspot imaging. Is 68Ga set up as an isotope on your scanner? Do you plan to use the same scanning protocol that you use for your FDG patients? Considering that the recommended injected dose to a patient is a maximum of 5.4 mCi, will you need to increase your imaging time? What about your reconstruction parameters? Will you need to adjust your filters and other reconstruction parameters?
What about your in-house radiopharmacy (hot lab or RPL)? Does your dose calibrator have 68Ga set up as a push button, or are you going to need to use the calibration factor each time you assay a dose? Do you need to modify your daily start-up procedures to include a constancy and accuracy check of the 68Ga setting in addition to 137Cs and 18F? Is there adequate storage space for the additional leaded carriers? How are you going to separate the 68Ga from the 18F doses to prevent misadministration? What about your pharmacy manager program? Is your pharmacy manager software set up to receive and dispense 68Ga-DOTATATE? Do you need to add 68Ga to the dose manager so that you can record the daily constancy and accuracy checks?
Being familiar with Octreoscan, we can share with clinicians and patients that Netspot has improved sensitivity and specificity over Octreoscan with less radiation. An added advantage for patients and referring physicians is that the scans are performed and reported on the same day, with decreased imaging time compared to Octreoscan, which is a multi-day study. At our institution, we instruct patients to have only clear liquids for 2 hours prior to the exam. Whether or not to discontinue octreotide therapy should be discussed by the nuclear medicine physician and referring physician. The SNMMI 68Ga-DOTAXXXX Imaging Manual (2014) advises discontinuing octreotide therapy (when possible and not contraindicated) to avoid possible somatostatin receptor blockade. The time interval between interruption of therapy and 68Ga-DOTATATE injection depends on the type of drugs used: 1 day is suggested for octreotide and 3–4 weeks for long-acting analogs. When octreotide therapy is not discontinued, it can change in the biodistribution pattern of the Netspot. However, there are also literature reports of improved tumor-to-background ratios following pretreatment with octreotide. Again, this is something that has to be decided by the nuclear medicine physician and referring physician.
Patient imaging techniques Netspot are similar to 18F-FDG oncologic studies. The patient is injected, with uptake time of 50 to 70 minutes followed by the start of imaging. At our institution, due to the lower injected activity as compared to18F-FDG oncologic studies, we acquire Netspot for 4 to 5 minutes per bed position rather than 2 to 3 minutes. Also, we include the skull vertex rather than imaging to the base of skull. The correct biodistribution for Netspot consists of pituitary, liver, and spleen uptake with no brain uptake. Including the vertex ensures that the pituitary is in the first bed position. If there is no pituitary uptake, it’s time to notify your supervising physician immediately.
PET imaging continues to evolve, with advances in technology such as PET/CT and PET/MR to a new generation of PET radiopharmaceuticals that offer physicians new ways to images disease with PET. Netspot is one of the first of these new PET radiopharmaceuticals, and it changed how we as technologists manage our PET department. The technologist must be at the vanguard in introducing these new radiopharmaceuticals and working out how to assimilate the new procedures into our current workload.
Barry Shulkin, MD, MBA, was the inaugural speaker supported by the new PET COE Speaker’s Bureau. His talk was entitled Use of PET/CT in Pediatrics with Applications to be Used in Adults and occurred on March 23, 2019, in Arlington, TX, at the annual meeting of the Southwestern Chapter of SNMMI.
If your group is interested finding a future PET topic speaker, please see the details here. If you are interested in applying to the Speakers’ Bureau for funding or would like more information, please contact Teresa Ellmer.
|Left: Dr. Barry Shulkin, St. Jude’s, Memphis, TN, and Dr. Lorraine De Blanche, Southwestern Chapter of SNMMI, board member and 2019 Program Chair. Right: Dr. Shulkin during his presentation.
The PET Center of Excellence acknowledges Gary Ulaner, MD, PhD, as one of the first Hal O’Brien Rising Star Award Winners. Dr. Ulaner was nominated by the PET Center of Excellence.
The Hal O’Brien Rising Star award is intended for early career professionals identified to have the potential to become future leaders in nuclear medicine. The award provides $1,000 for travel expenses to the High Country Nuclear Medicine Conference (HCNMC), where the awardee is presented with a plaque and invited to participate in the program. The award is targeted for junior faculty, post-docs, and fellows identified by councils and centers of the SNMMI as rising stars.
The SNMMI Annual Meeting will be held June 22-25 in Anaheim, CA. Registration details can be found at http://www.snmmi.org/am2019.
The PET Center of Excellence is pleased to announce that Hossein Jadvar, MD, PhD, MPH, MBA, FACNM, FSNMMI, is the recipient of the 2019 Peter E. Valk, MD, Memorial Lectureship and Award. Dr. Jadvar will receive his award and present a lecture, entitled PET in Prostate Cancer: Frontierland and Tomorrowland, on Monday, June 24, at 3:00 pm during the SNMMI Annual Meeting.
The PET Center of Excellence seeks volunteers for two key initiatives (see below). If you are interested in participating on these working committees, please email Teresa Ellmer (email@example.com), associate director of governance. Please include a one-paragraph statement of interest and your CV.
PET/MRI Working Group: The PET Center of Excellence has launched a PET/MRI working group that will bring together members from across SNMMI. PET/MRI is an emerging imaging modality that requires significant development to realize its full potential in research and clinical care. The objective of the SNMMI PET/MRI Working Group is to support the development of PET/MRI and to educate physicians, researchers, and technologists. It will support educational activities at the Annual Meeting, webinars, and workshops jointly sponsored with other organizations. PET/MRI is truly an intersociety modality requiring input from multiple organizations to help accelerate its development and clinical adoption. The new PET/MRI group will work with the SNMMI community to address member needs and help advance PET/MRI.
Theranostics Task Force: The purpose of this committee is to evaluate, promote, and educate about the use of PET as an adjunct for therapies. While the primary therapeutic focus is targeted radionuclide therapy (TRT), this working group will have a wider focus on any role of PET related to therapy (i.e., patient selection and/or radiation treatment planning). Current projects are examining the role of 68Ga-DOTATATE for 177Lu-DOTATATE therapy in NETs and the role of 18F-FDG in radiation treatment planning.
The PET COE Board of Directors held a retreat on Sunday, June 2, in Boston, Massachusetts. Special thanks to Vasken Dilsizian, MD, who attended on behalf of the SNMMI Board of Directors.
|PET COE Retreat, May 2019. Pictured, from left: Maria Liza Lindenberg, MD; Shelley Nicole Acuff, CNMT, RT(R)(CT); Gary Ulaner, MD, PhD, FACNM; Helen Nadel, MD, FRCPC; Todd Peterson, PhD; Twyla Bartel, DO, MBA, FACNM; Jian (Michael) Q. Yu, MD, FRCPC, FACNM; Michael V. Knopp, MD, PHD; Medhat M. Osman, MD, PhD, MS; Katherine Zukotynski, BASc, MD, FRCPC; and Ben Greenspan, MD, FACNM, FACR, FSNNMI.|
New Radiotracer Can Identify Nearly 30 Types of Cancer, with Future Potential for Therapeutic Application
A novel class of radiopharmaceuticals has proven effective in non-invasively identifying nearly 30 types of malignant tumors, according to research published in the June issue of The Journal of Nuclear Medicine. Using 68Ga-FAPI positron emission tomography/computed tomography (PET/CT), researchers were able to image a wide variety of tumors with very high uptake and image contrast, paving the way for new applications in tumor characterization, staging and therapy.
The 68Ga-FAPI radiotracer targets cancer-associated fibroblasts, which can contribute up to 90 percent of a tumor’s mass. Many cancer-associated fibroblasts differ from normal fibroblasts by their specific expression of the fibroblast activation protein, or FAP. FAP-specific inhibitors were first developed as conventional anticancer drugs; now they have been advanced into tumor-targeting radiopharmaceuticals.
|Figure. Maximum-intensity projections of 68Ga-FAPI PET/CT in patients reﬂecting 15 different histologically proven tumor entities (sorted by uptake in descending order). Ca = cancer; CCC = cholangiocellular carcinoma; CUP = carcinoma of unknown primary; MTC = medullary thyroid cancer; NET = neuroendocrine tumor.|
In the retrospective study, researchers used PET/CT to image 80 patients with 28 different kinds of cancer, aiming to quantify 68Ga-FAPI uptake in primary, metastatic or recurring cancers. All patients were referred for experimental diagnostics by their treating oncologists because they were facing an unmet diagnostic challenge that could not be solved sufficiently with standard methods. The injected activity for the 68Ga-FAPI examinations was 122-312 MBq, and the PET scans were initiated one hour after injection. Tumor tracer uptake was measured by SUVmean and SUVmax.
All patients tolerated the examination well. As the overall SUV mean, median and range of 68Ga-FAPI in primary tumors and metastatic lesions did not differ significantly, researchers analyzed all results in one group.
The highest average SUVmax (SUVmax >12) was found in sarcoma, esophageal, breast, cholangiocarcinoma and lung cancer. The lowest 68Ga-FAPI uptake (average SUVmax <6) was observed in pheochromocytoma, renal cell, differentiated thyroid, adenoid cystic and gastric cancers. The average SUVmax of hepatocellular, colorectal, head-neck, ovarian, pancreatic and prostate cancer was intermediate (SUVmax 6-12). In addition, the tumor-to-background ratios were more than three-fold in the intermediate group and more than six-fold in the high-intensity uptake group, resulting in high image contrast and excellent tumor delineation.
“The remarkably high uptake of 68Ga-FAPI makes it useful for many cancer types, especially in cases where traditional 18F-FDG PET/CT faces limitations,” said Uwe Haberkorn, MD, professor of nuclear medicine at the University Hospital of Heidelberg and the German Cancer Research Center in Heidelberg, Germany. “For example, low-grade sarcomas generally have a low uptake of 18F-FDG, causing an overlap between benign and malignant lesions. In breast cancer, 18F-FDG PET/CT is commonly used in recurrence, but not generally recommended for initial staging. And for esophageal cancer, 18F-FDG PET/CT often has only a low to moderate sensitivity for lymph node staging.”
In contrast to 18F-FDG PET/CT, 68Ga-FAPI PET/CT can be performed without specific patient preparation such as fasting or recline during uptake time. This is a potential operational advantage for 68Ga-FAPI PET/CT, as it stands to improve patient comfort and accelerate work-flow.
According to Haberkorn, 68Ga-FAPI offers the possibility of a theranostic approach in the future. “Cancer associated fibroblasts have been described as immunosuppressive and as conferring resistance to chemotherapy, which makes them attractive targets for combination therapies,” he said. “Because the 68Ga-FAPI tracers contain the universal DOTA-chelator, it is possible to label them with therapeutic radionuclides whose half-life fits to the tumor retention time of the carrier molecule. Since the tracer has been observed to accumulate in several important tumor entities, there may be a huge field of therapeutic application to be evaluated in the future.”
The authors of “68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer” include Clemens Kratochwil, Thomas Lindner, Labidi Abderrahim, Walter Mier, Hendrik Rathke, Manuel Röhrich and Frederik L. Giesel, Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany; Paul Flechsig, Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany, and Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany; Annette Altmann, Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany, and Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany; Sebastian Adeberg, Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany, and Heidelberg Institute for Radiation Oncology, Heidelberg, Germany; Hauke Winter, Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany, and Department of Surgery, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany; Peter K. Plinkert, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany; Frederik Marme, Department of Obstetrics and Gynecology, University Hospital Heidelberg, Heidelberg, Germany, and Department of Obstetrics and Gynecology, University Hospital Mannheim, Mannheim, Germany; Matthias Lang, Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany; Hans Ulrich Kauczor, Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany, and Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany; Dirk Jäger, Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany, and Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center, Heidelberg, Germany; Jürgen Debus, Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany, Heidelberg Institute for Radiation Oncology, Heidelberg, Germany, and Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center, Heidelberg, Germany; and Uwe Haberkorn, Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany, Translational Lung Research Center Heidelberg, German Center for Lung Research, Heidelberg, Germany, and Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany.
June 22 – 25, 2019
SNMMI 2019 Annual Meeting
July 13 – 14, 2019
Viva Las Vegas 2019
Las Vegas, NV
August 24 – 25, 2019
Hands-On Nuclear Medicine Physics Workshop
Iowa City, IA
September 9, 2019
BNMS Autumn Meeting 2019
September 12 – 14, 2019
Memorial Sloan Kettering 5th Annual Oncologic FDG PET/CT CME Course
New York, NY
September 15 – 18, 2019
2019 ASTRO Annual Meeting
West Chicago, IL
September 21 – 22, 2019
2019 Eastern Great Lakes Chapter SNMMI Annual Meeting
London, Ontario, Canada
September 24 – 27, 2019
65th Annual Scientific Meeting - Canadian Organization of Medical Physicists
Kelowna, British Columbia, Canada
October 26 – 28, 2019
SNMMI/ISMRM PET/MR Workshop
New York, NY