Thomas Beyer: First, it is recommended (see EANM GL by Boellaard et al) to scan PET/CT patients with their arms up. The techs should pre-inform the patients about the expected improvements in diagnostic quality of the scan. In case the arms cannot be moved above the head, ultra-low dose CT should be avoided; you could work with higher dose levels and ensure that alt. means of dose reduction (tube current modulation etc.) are turned on.

Thomas Beyer: Feel free to call it minimally invasive. The same would apply for CT nd MRI if IV contrast agents are being used. It is, however, well accepted to refer to PET/CT (and related hybrid imaging methods) as “non-invasive”. This is a reference to a physical action and has nothing to do with “radioactivity”.

Thomas Beyer: There is not too much radiation, if diagnostically indicated. Individual dose levels are monitored and regulated by national guidelines. Multiple scans, if diagnostically indicated, are covered as well.

Thomas Beyer: In short, a great research tool. The search is still on for the clinical key applications in oncology, with a tendency towards prostate cancer. Feel free to scout for the respective literature, such as: https://www.ncbi.nlm.nih.gov/pubmed/26742709 .

Thomas Beyer: PET imaging centres should fulfill a purpose: to help patients in need. If there are many patients to be diagnosed with PET then perhaps multiple PET scanners are needed (depending on the throughput regulations and other factors). Whether or not these systems are situated in one or multiple places depends on the owners, the accessibility and other factors. No a priori guidance.

Thomas Beyer: Price. Complexity. Lack of routine key applications.

Thomas Beyer: Please consult: https://www.ncbi.nlm.nih.gov/pubmed/25452219. In short, SUVmax is prone to noise effects. SUVmean disregards heterogeneities. SUVpeak is to be preferred. Whatever you do, stick to one value when reporting follow-up.

Barbara Malene Fischer: It depends very much on the location and patient history, but also on the avidity of the hot-spot. If a patient had a solitary intensely FDG-avid focus in a vertebral body (centrally) or in a pelvic bone (e.g. right or left pubic bone) I would most likely report it as suspicious for malignancy, even if there was no morphological changes on CT. However, if a patient had 2-3 foci on adjacent ribs I would be les worried.

Barbara Malene Fischer: You need to consider FDG-avidity, pattern of uptake, size, location (together with the location of the primary tumour).

Barbara Malene Fischer: I would start with PET/CT.

Barbara Malene Fischer: I personally prefer CT with contrast, but many institutions – mainly due to financial and/or logistical reasons – do a low-dose CT without contrast.

Barbara Malene Fischer: Very useful if possible. However RT needs to start relatively shortly (approx. <4 weeks) after staging and the PET/CT should be done in treatment position.

Barbara Malene Fischer: You can’t discriminate between a benign and malignant nodule based on the SUV alone, but need to consider many other factors as well.

Barbara Malene Fischer: That will depend on the type of cancer you are looking for.

Barbara Malene Fischer: We don’t on a standard FDG PET/CT.

Barbara Malene Fischer: You can’t discriminate between malignant lymph nodes and e.g. sarcoidosis in the mediastinum based on the SUV alone. However, the pattern of uptake will often differ (e.g. lambda- sign in sarcoidosis) – but if the patient is not known with sarcoidosis it will most often be necessary with an EBUS to rule out e.g. lymphoma.

Barbara Malene Fischer: The recommendation is > 2 weeks after chemotherapy. The truth is we don’t really know.

Barbara Malene Fischer: This is suggested in the literature. However, the clinical benefit compared to the more complex logistics is not convincing.

Barbara Malene Fischer: I would start with FDG-PET/CT.

José Vercher-Conejero: First, you should evaluate both images (AC and non-AC) side by side and try to discart possible artifacts due to the CT portion (though mainly, these artifacts generate the opposite, uptake on the AC-PET images and no abnormal uptake on the non-AC-PET. If this artifact is due to respiratory motion, repeating the BED on that anatomical region or using a respiratory gating mechanism could solve the problem.

José Vercher-Conejero: No. SUVmax should not only has to be the only information to take into account when reporting a PET/CT scan…you also have to evaluate lymph node uptake distribution (bilaterality), location of the lung nodule/mass, clinical history, etc. Some reactive (immflamatory) lymph nodes may have a higher uptake than 3 and be benign.

José Vercher-Conejero: Evaluation of FDG metabolism of bladder lesions can be difficult mainly because the urinary excretion of FDG interferes with visualization of the primary bladder tumor. However, it’s important to keep in mind that the patient should void the bladder just before the PET adcquisition. Besides that, placing a urinary catheter on the patient or delayed pelvic images after diuretic administration and oral hydration may help.

José Vercher-Conejero: Some malignant processes might show low FDG uptake such as renal cell carcinoma, some lung tumors (carcinoid, lepidic ADK), hepatocellular carcinoma, mucinous neoplasms, indolent lymphomas, well-differenciate neuroendocrine tumors and well-differenciate thyroid tumors or some breast cancer histology (lobular).

José Vercher-Conejero: Sometimes it can be difficult to differentiate it if we only rely on FDG uptake. Anatomical infomation should be evaluated along with the lesion uptake to be more specific.

José Vercher-Conejero: On a normal basis, the CT acquisition takes few second to be performed and the BED from the PET usually takes around 2-3 min depending on the PET/CT equipment, so during this PET acquisition the patient has an respiratoy motion.

José Vercher-Conejero: When evaluating treatment response with PET/CT in a patient who’s receiving this type of drug, it’s important to keep in mind that if there are doubts of pseudoprogressionon vs. progression, a follow-up scan might be helpful. I recommend you to read a review a recent published paper FDG PET/CT for assessing tumour response to immunotherapy from Aide et al. (Eur J Nucl Med Mol Imaging. 2019; 46(1): 238–250).

José Vercher-Conejero: If the CT portion doesn’t help much, you can repeat the BED position re-evaluating the FDG uptake and check if the fused image with the CT helps (uptake foci on a fat density tissue). Also, bilateral uptake (if present) and its distribution might help.

José Vercher-Conejero: I doubt this can happen due to all the advantages from PET/CT over SPECT/CT. Other discussion topic would the the opposite, if PET/CT can replace SPECT/CT…

José Vercher-Conejero: I agree with you, evaluation of FDG metabolism of bladder lesions can be difficult mainly because the urinary excretion of FDG interferes with visualization of the primary bladder tumor. However, it’s important to keep in mind that the patient should void the bladder just before the PET acquisition. Besides that, placing a urinary catheter on the patient or delayed pelvic images after diuretic administration and oral hydration may help.

Myriam Wartski: Yes. As mentionned, ductal carcinoma have higher SUVmax than lobular carcinoma. Also, all factors of tumor aggressivity (ductal, SBR 3, high mitotic index, Triple negative phenotype, high Ki-67) are correlated with high SUV values.

Myriam Wartski: A moderate place because FDG PET/CT is generally used for visceral and bone metastasis assessment in one exam.

Myriam Wartski: This depends on the clinical problem.

Myriam Wartski: in neoadjuvant setting, timing of response evaluation with FDG PET/CT depends on the chemotherapy regimen and is variable among studies and trials.

Myriam Wartski: It is not routinely used, in fact.

Myriam Wartski: Yes, from stage II and above.

Myriam Wartski: Lobular.

Myriam Wartski: PET/CT.

Patrick Veit-Haibach: EUS is done clinically almost always anyway. It has the much higher resolution and therefore defines the depth of invasion usually better than cross sectional imaging. Also, small peritumoral lymh nodes are usually better seen. The PET/CT is for other local lymph node metastases and distant metastases detection. Also at baseline the PET/CT defines the uptake which can then be compared after neo-adjuvant radio/chemotherapy. The delta between the FDG uptake pre and post therapy is predictive of the overall prognosis.

Patrick Veit-Haibach: You can, but I do not see the use in that. Usually you would give positive oral contrast for the GI tract for the abomdinal CT part of the examination. An extra barium swallow would maybe show some ulceration of the tumour, but those tumours are usually larger anyway. And you would have captured that information with the EUS before anyway.

Patrick Veit-Haibach: Mucinous tumours are usually gastric tumours, not purely esophageal tumours. Mucinous tumours are only FDG postive in about 50% of cases, so there is no routine use recommended in those tumour entities.

Patrick Veit-Haibach: Maybe you’ll find one or the other positive esophageal tumour, but I have not seen that so far. I am not aware of a case report about that either. It is not recommended for any routine use in this disease.

Jean-Noël Talbot: Not on basis of the standard image itself at 60 min, but of course the clinical context will help. Some authors advised to compare with a delayed acquisition (120 min or so), an increase of SUV favouring malignancy but the enhancement of specificity is not obvious and this procedure is difficult in real life if you plan to perform at least 16 PET/CTs per day.

Jean-Noël Talbot: Major with FDG. To detect myocardial involvement, patients being prepared with a low carbohydrate regimen, to specify disease spread and to objectivate response to treatment. It is an official indication in the Core Summary of Product Characteristics of FDG in EU.

Jean-Noël Talbot: I am not aware of a published series for this indication. FDG has a reduced performance in the base of the skull due to its uptake by brain cortex. In other segments of the spine, FDG is sensitive to detect osteomyelitis and also to check the response for treatment and to determine whether it may be stopped.

Jean-Noël Talbot: It is very difficult if a baseline FDG PET/CT has not been performed for staging. This is highly recommended in France, even though some authors in Germany have questioned its indication.

Jean-Noël Talbot: This indication is listed in the FDG SmPC of EMA only for the hip, not for the knee or the shoulder. If negative, the NPV is good enough to rule out an active infection unless there are major arguments favouring this diagnosis. If positive, a differential diagnosis with pure inflammation should be made, considering the location of the foci (references in my presentation) and the presence of foci in the soft tissue. In difficult cases, labelled leucocytes scintigraphy cannot be avoided. A pure tracer of infection is currently lacking for PET but researches are underway.

Jean-Noël Talbot: FDG can play a role in the diagnosis of vascular and cardiac valves infection. It is part of the list of indications. Elements of differential diagnosis have been published and references are given in my presentation even though I had no time to comment on that. The differential diagnosis between infection of a vascular prosthesis and vasculitis is usually easy, thanks to the CT landmarking the prosthesis and since vasculitis is usally diffuse in several vessels.

Jean-Noël Talbot: Sure! If the meds result in some incomplete response or relapse when stopped, there is a risk that the lesions would be partially stunned with a poor contrast as background.

Jean-Noël Talbot: I have no such data present. To the best of my knowledge it has not been published.

Jean-Noël Talbot: This indication is listed in the FDG SmPC of EMA only for the hip, not for the knee or the shoulder. If negative, the NPV is good enough to rule out an active infection unless there are major arguments favouring this diagnosis. If positive, a differential diagnosis with pure inflammation should be made, considering the location of the foci (references in my presentation) and the presence of foci in the soft tissue. In difficult cases, labelled leucocytes scintigraphy cannot be avoided. A pure tracer of infection is currently lacking for PET but researches are underway.

Probably the writing party of he EANM guidelines was composed of NM specialists with an advanced practice. In the real world it is far easier to find a slot of FDG PET than a department of NM which performs leucocyte scintigraphy with in vitro labelling which is the reference method. So FDG PET may be the 1st line and it is more sensitive than bone SPECT.

Jean-Noël Talbot: In my experience this is not a frequent case, perhaps because patients with lesions typical for malignancy on a previous CECT are not all referred to PET/CT for staging or restaging. Of course it depends whether you have chosen the right tracer for PET. FDG is not sensitive for prostate cancer or well differentiated HCC or renal cancer or brain tumors or bronchoalveolar cancer or mucinous producing cancer or neuroendocrine neoplasias for which more sensitive tracers are available as FCH or PSMA or somatostatin ligands or may FAPI in future.

Helen Nadel: PET/CT can of course detect very small metabolically active metastases. Germ cell tumors are usually FDG avid as are their mets to include all forms. Size would not determine if metastasis were visible possibly

Helen Nadel: Global as in total body vertex to toes? The reason for this is that pediatric malignant disease can often occur distally in children, i.e. below elbows and knees. The time to add on the few bed positions can sometimes make a difference in staging. However, we do routinely decrease our time for bed postion in the head and extremities from torso. We would routinely decrease from 2 min for torso to 1 min for head and extemities without prior knowledge of disease in these areas. Recently we have had an IAEA publication that does state that in PEDIATRIC LYMPHOMA the incidence of disease that may upstage the patient is low enough to restrict to ‘eyes to thighs” imaging but I caution this is validated currently only for lymphoma. Reference : Cerci JJ, Etchebehere EC, Nadel H, Brink A, Bal CS, Rangarajan V, Pfluger T, Kagna O, Alonso O, Begum FK, Mir KB, Magboo VP, Menezes LJ, Paez D, Pascual TN. Is True Whole-Body (18)F-FDG PET/CT Required in Pediatric Lymphoma? An IAEA Multicenter Prospective Study. J Nucl Med. 2019 Aug;60(8):1087-1093. doi:
10.2967/jnumed.118.222299. Epub 2019 Jan 25. PubMed PMID: 30683766.

Helen Nadel: FDG is of course non specific so careful correlation with history and physical as well as laboratory results is mandatory. Benign disease such as inflammation can usually be less focally avid but there is no SUV or visual cut-off. In Sarcoma for instance it would be usually an order of magnitude greater FDG avidity for osteosarcoma or Ewing sarcoma. Rhabdomyosarcoma can be less avid in some cases but all are “usually” more avid than inflammation. Ultimately, biopsy is required to confirm a tissue diagnosis.

Helen Nadel: mIBG is still the mainstay for staging and response assessment for neuroblastoma as treatment protocols require a Curie score or SIOPEN score be given which is currently only vailidated for mIBG and not PET. 10% of all neuroblastoma patients may be mIBG negative in this instance PET with FDG or even Ga 68-DOTA or F-18 DOPA may be utilized. A newer indication for correlation with FDG PET is when there is persistent mIBG activity in patients who have no other evidence of active or progressive disease either clinically or biochemically. These patients might still have abnormal mIBG uptake that has not changed over a long time even when off therapy. The as yet not validated use for FDG PET is that if the lesions are negative on FDG while still hot on mIBG this may now have differentiated to more benign disease such as ganglioglioma or other benign neural crest tissue. Concordance on mIBG and FDG could suggest disease still has malignant potential and may require biopsy to confirm if now benign neural crest tissue that still remains only mIBG positive. Reference: Sharp SE, Shulkin BL, Gelfand MJ, Salisbury S, Furman WL. 123I-MIBG scintigraphy and 18F-FDG PET in neuroblastoma. Journal of Nuclear Medicine. 2009 Aug 1;50(8):1237-43.

Helen Nadel: There are some centers that are starting to use this. We plan to start such a program in conjuction with cardiology and cardiac surgery here at Stanford but have not started as yet. It can be done as it is in adults with some modifications.

Helen Nadel: If the lung lesions are FDG avid, it will be seen on the scan. Some specific MRI sequences can visualze the lung with pretty good sensitivity. We use a propeller and T1g MRI sequence routinely.

Helen Nadel: The choice of radiopharmaceutical depends on the indication for the scan. We recently had a case of unusual undifferentiated carcinoid tumor that was very avid on FDG PET and yet not as avid on Ga-68 dotatate reflecting the undifferentiated histology of the tumor. In general there is more limitation to the neuroendocrine tumor types for the Ga radiophar. in neuroendocrine tumors also depends on tumor type and histology see answer above regarding neuroblastoma.

Clemens Cyran: Considering that both criteria are generally used in a study setting, the criteria that are defined in the study protocol should be followed. However, as also stated in the lecture, eventually morphological and functional information contributes to superior diagnostic accuracy.

Clemens Cyran: If monitoring of immunotherapy relies on conventional CT, time points for response monitoring should be carefully aligned with the oncologist and results need to be interpreted along the lines of immunotherapy criteria such as iRECIST with particular regard to uPD.

Clemens Cyran: Indeed, there are recent studies that show predictive values of FDG PET/CT in patients with MM with regard to PFS and OS.

Clemens Cyran: This depends on the criteria applied for assessment. Generally, when monitoring immunotherapy the concepts of dedicated criteria with particular regard to unconfirmed/confirmed progression should be kept in mind.

Katrine Riklund: In general, more inforamtion is gained with SPECT and it gives better information about the topography. On a patient level, the information on planar scint is most often accurate. As a problem solver, an added SPECT of the pelvic region is worth doing.

Katrine Riklund: Yes, antiandrogen therapy might reduce the uptake but prostate cancer is a multi-faced disease so the effect differ between patients.

Katrine Riklund: Yes, it could.

Katrine Riklund: The results so far show that F-PSMA is at least as good as Ga-PSMA with similar T/NT ratios. One added advantage is the low urinary excretion at time of scanning which makes F-PSMA superior over Ga-PSMA for evalutaion of lesions close to the bladder.

Katrine Riklund: Too small tumour burden, too low expression of PSMA.

Katrine Riklund: It might accumulate in fractures and degenerative changes.

Katrine Riklund: NSCLC, granulomatous lesions, ganglions, often with lower intensity and the prostate cancer met lesions.

Harun Ilhan: High PSMA-ligand uptake in patients with severe bone marrow involvement plays a crucial role in terms of related toxicity. The relatively long distance of Lu177 in tissue can be related to higher toxicity rates. However, there is also data supporting a displacement of PSMA-ligand uptake in tumor and active bone marrow, thus sparing healthy bone marrow. Nonetheless the range of alpha-emitters (e.g. Ac225), which is just on cellular level should be related with less toxicity. Some therapy algorithms thus suggest to start PSMA-ligand therapy using Ac225 in patients with severe bone (marrow) involvement.

Harun Ilhan: Both therapies have different targets and mechanisms. SIRT can be used to deliver high radiation doses on a capillary level while PRRT targets Somatostatin-Receptors on the tumor cell surface. As SIRT is a liver only therapy option, it should only be used in patients where tumor involvement of the liver is dominant. In case of high tumor load outside the liver (e.g. bone mets, lymph nodes / peritoneal) PRRT is the method of choice. Nonetheless there is data supporting a combination (e.g. stable metastases outside the liver and progression of liver metastases).

Harun Ilhan: There is more and more data supporting that Lu-177 PRRT seems to be more effective in patients with Paraganglioma / Phäochromocytoma. However, pretherapeutic imaging using Ga-68/F-18 labeled TATE/TOC compounds and I-123 MIBG is highly important. The method of choice should depend on tumor uptake in pretherapeutic imaging.

Harun Ilhan: The BG-75 cyclotron could be of high value for sites with relatively low patient numbers (e.g. first installation of PET/CT or PET/MRI scanners).

Harun Ilhan: As most BC metastases show more or less elevated Glucose-Metabolism, FDG-PET/CT can be used for staging and shows good sensitivity and specificity. Novel tracers, targeting for instance Estrogen-Receptors are under clinical investigastion (e.g. F18-Fluorestradiol) and can be of high value regarding patient selection for hormonal treatment options.