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Abstract

Purpose

Tumor resection represents the first-line treatment for symptomatic meningiomas, and the extent of resection has been shown to be of prognostic importance. Assessment of tumor remnants with somatostatin receptor PET proves to be superior to intraoperative estimation with Simpson grading or MRI. In this preliminary study, we evaluate the prognostic relevance of postoperative PET for progression-free survival in meningiomas.

Methods

Results

Conclusion

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Methods

Study population

Tumor resection and radiation therapy

Imaging

Statistical analysis

Comparison of baseline variables between patients with positive or negative PET was performed using the chi-squared test and Fisher’s exact test for two or more categorical variables. The D’Agostino-Pearson omnibus normality test was utilized to test for normal distribution and equal variance in continuous data. The unpaired Student t-test was used to assess differences between two groups in case of parametric data, and the Mann–Whitney U-test was calculated for nonparametric variables. For paired data such as time intervals between different imaging modalities in each respective patient, the paired t-test and Wilcoxon matched-pairs signed rank test were utilized. Numerical data are described as mean ± standard error of the mean, and range is given, if not indicated otherwise. Statistical analyses were performed using a standard software package (SPSS Statistics version 25). The significance level was set at p ≤ 0.05.

Results

Patient and tumor characteristics

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Full size table

Imaging and extent of resection

Outcome

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Predictors for outcome

PET

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Next, we wanted to evaluate the importance of PET findings in case of “complete” tumor resections as judged by the operating surgeon and corresponding to SG I and II (n = 34). Here, tumor residuals on PET proved to be strongly associated with tumor progression (*p = 0.004), and a positive predictive value of 40% was reached, while the negative predictive value remained 100%. Again, PFS was significantly higher in patients with negative PET findings (*p = 0.014; Fig. 3C).

MRI

Five of seven patients with tumor recurrence showed no evidence of tumor remnants on postoperative MRI. Fisher’s exact test showed no association between tumor remnants on MRI and tumor progression/recurrence (p = 0.683). Sensitivity and specificity were 29% and 55%, respectively, with a positive predictive value of 10% and a negative predictive value of 82%. Exclusion of patients who received postoperative radiotherapy resulted in a positive predictive value of 14%. Detection of tumor remnants on MRI was not associated with less favorable outcome (p = 0.883; Fig. 3D).

Simpson grading

Simpson grading was not associated with tumor progression/recurrence (p = 0.414). Six of 34 meningiomas (18%) displayed tumor recurrence after SG I or II resections, and one of 15 patients (7%) had tumor progression after SG IV resection corresponding to a sensitivity and specificity of 14% and 67%, respectively. Of note, this patient did not receive postoperative radiotherapy. These findings held true when comparing only patients homogenously treated with a watch-and-wait approach (n = 42, p = 0.999). “Complete” tumor resection (SG I and II) was not associated with improved PFS (p = 0.590).

Implications for radiotherapy

Seven of 46 patients (14%) were treated with FSRT. In six of seven patients, radiotherapy planning data were available. Here, GTV as delineated on PET was significantly higher in comparison to MRI GTV (12.1 ± 3.3 cm³ versus 7.8 ± 2.7 cm³; *p = 0.032; Table 2). PET was especially helpful in determining bony tumor involvement, leading to a different PTV in five of six patients (83%; Fig. 4A, B).

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Discussion

This, in turn, is relevant from a health economics’ perspective. As SSTR2 PET and its associated ligands become more cost-effective and can be offered on a widespread basis, a reduction in the frequency of postoperative surveillance scans via MRI considering its limitations in predicting tumor recurrence has to be evaluated. In this context, further cost-effectiveness analyses are warranted.

The limitations of our study included the limited sample size and different adjuvant treatment strategies that were applied in our patient cohort depending on extent of resection. No additional sample size calculations and success thresholds for survival data were defined a priori, possibly introducing bias. Large prospective studies are needed to validate our promising findings in this preliminary study and take postoperative treatment strategies into account.

Data availability

The data presented in this study are available on request from the corresponding authors. The data are not publicly available due to the guidelines of the Institutional Review Board of the Ludwig-Maximilians-University in Munich.

Funding

Open Access funding enabled and organized by Projekt DEAL.

Author information

Authors and Affiliations

1. Department of Neurosurgery, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany

   Nico Teske, Annamaria Biczok, Stefanie Quach, Joerg-Christian Tonn, Christian Schichor & Moritz Ueberschaer

2. German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany

   Nico Teske, Annamaria Biczok, Stefanie Quach, Franziska J. Dekorsy, Maximilian Niyazi, Joerg-Christian Tonn, Nathalie L. Albert, Christian Schichor & Moritz Ueberschaer

3. Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany

   Franziska J. Dekorsy & Nathalie L. Albert

4. Institute of Neuroradiology, LMU University Hospital, LMU Munich, Munich, Germany

5. Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany

   Raphael Bodensohn & Maximilian Niyazi

6. Bavarian Center for Cancer Research (BZKF), Erlangen, Germany

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Contributions

Study concept and design: J.C.T.; C.S; M.U.

Data collection: A.B.; S.Q; F.J.D; R.F; R.B.; N.L.A.; M.U.

Analysis and interpretation of data: N.T.; A.B.; S.Q.; F.J.D.; R.F.; R.B.; M.N.; J.C.T.; N.L.A.; C.S.; M.U.

Drafting of the manuscript: N.T.; J.C.T.; C.S.; M.U.

Revising of the manuscript: N.T.; A.B.; S.Q.; F.J.D.; R.F.; R.B.; M.N.; J.C.T.; N.L.A.; C.S.; M.U.

Corresponding authors

Correspondence to
Nico Teske or Moritz Ueberschaer.

Ethics declarations

Ethics approval and consent to participate

This is an observational study. Study protocol and design were approved by the Institutional Review Board of the Ludwig-Maximilians-University in Munich, Germany (18-007), and patients’ informed consent was obtained.

Competing interests

Nico Teske: no disclosures

Annamaria Biczok: no disclosures

Stefanie Quach: no disclosures

Franziska J. Dekorsy: no disclosures

Robert Forbrig: no disclosures

Raphael Bodensohn: no disclosures

Maximilian Niyazi: honoraria for lectures from BrainLab

Joerg-Christian Tonn: research grants from Novocure and Munich Surgical Imaging, honoraria for lectures from BrainLab and CarThera, and royalties from Springer Publisher Intl.

Nathalie L. Albert: no disclosures

Christian Schichor: no disclosures

Moritz Ueberschaer: no disclosures

Additional information

Publisher’s note

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About this article

Cite this article

• Received23 April 2023

• Accepted12 August 2023

• Issue Date

Keywords

, Tara D. Barwick, , Andrea G. Rockall, , , , , Juan W. Valle, Richard A. Hubner, Mairéad G. McNamara, , , , , , , , , , Jingky P. Lozano-Kuehne, Eric O. Aboagye and

Journal of Nuclear Medicine

Abstract

Neuroendocrine neoplasms (NEN) are a heterogeneous group of malignancies arising from cells of the diffuse neuroendocrine system. Accurate diagnosis of primary lesion and staging the extent of disease dictates both management and prognosis, whereby patients with limited disease can undergo radical locoregional therapy, including surgery or ablation with curative intent, whereas systemic therapy is reserved for those with metastatic disease given with palliative intent (1). Accurate imaging is crucial. As 20%–50% of patients with NEN will have metastatic disease at presentation (2), there is a need for an imaging methodology that is both sensitive and widely accessible.

MATERIALS AND METHODS

Study Design and Participants

Procedures

PET Imaging Protocol

Image Interpretation

As the presence of liver metastases is an independent prognostic factor (15), subgroup analysis of SUV and TBR measurements of the liver lesions based on tumor size was performed.

Independent Reader Evaluations

Statistical Analysis

RESULTS

Baseline Characteristics

Baseline Characteristics of Patient Cohort (n = 45)

Comparison of [¹⁸F]FET-βAG-TOCA and [⁶⁸Ga]Ga-DOTA-Peptide PET

Lesion Analysis

Regional Analysis

Interreader Agreement

Liver Metastases

DISCLOSURE

This work was funded by Medical Research Council Developmental Clinical Studies grant MR/J007986/1. The authors acknowledge infrastructure support from the National Institute for Health Research Imperial Biomedical Research Centre and the Imperial College Experimental Cancer Medicine Centre. Rohini Sharma received grant funding from Incyte, AAA, Boston Scientific, and Terumo. Mairéad McNamara received research grant support from Servier, Ipsen, NuCana, and AstraZeneca, travel and accommodation support from AAA, Ipsen, and AstraZeneca, and speaker honoraria from AAA and AstraZeneca and is on the advisory boards for Incyte and AstraZeneca. Andrea Frilling received grants from Novartis, AAA, Ipsen, Sirtex, and Clifton, all unrelated to the submitted work. Angela Lamarca received travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan, Delcath Advanz Pharma, and Roche, speaker honoraria from Merck, Pfizer, Ipsen, Incyte, AAA/Novartis, QED, Servier, AstraZeneca, EISAI, Roche, Advanz Pharma, and MSD, advisory and consultancy honoraria from EISAI, Nutricia, Ipsen, QED, Roche, Servier, Boston Scientific, Albireo Pharma, AstraZeneca, Boehringer Ingelheim, GENFIT, TransThera Biosciences, Taiho, and MSD, and principal investigator–associated institutional funding from QED, Merck, Boehringer Ingelheim, Servier, AstraZeneca, GenFit, Albireo Pharma, Taiho, TransThera, and Roche and is a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. Juan Valle received personal fees from Agios, AstraZeneca, Baxter, Genoscience Pharma, Hutchison Medipharma, Imaging Equipment Ltd (AAA), Incyte, Ipsen, QED, Servier, Sirtex, and Zymeworks and grants, personal fees, and nonfinancial support from NuCana, all outside the submitted work. Richard Hubner received consultancy fees from Beigene, Ipsen, and Novartis and travel and accommodation support from Roche. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. No other potential conflict of interest relevant to this article was reported.

KEY POINTS

PERTINENT FINDINGS: In a prospective, noninferiority study in 45 patients with histologically confirmed NET, we observed excellent correlations between both tracers with no difference across median SUV_max.

Footnotes

• © 2024 by the Society of Nuclear Medicine and Molecular Imaging.

References

• Received for publication September 22, 2023.
• Accepted for publication December 19, 2023.

Citation, DOI, disclosures and article data

Morgan M, Elfeky M, Yu Y, et al. Gallium-68 DOTATATE. Reference article, Radiopaedia.org (Accessed on 17 Jul 2024) https://doi.org/10.53347/rID-62034

Gallium-68 DOTATATE​​ (or Ga-68 DOTATATE) is a PET radiotracer that is a form of somatostatin-receptor (SSTR) functional imaging. It is most commonly used for evaluating primary and metastatic well-differentiated neuroendocrine tumors. There are also emerging uses for evaluating other somatostatin-expressing conditions, such as meningiomas or sarcoidosis ⁵.

Gallium-68 DOTATATE is synthesized from three main components:

1. gallium (Ga) radiotracer

2. linked, via a chemical macrocyclic chelator, known as DOTA (or tetraxetan; IUPAC name: 1,4,7,10-tetraazacyclododecane-tetraacetic acid)

3. to the short-chain peptide Tyr3-octreotate (TATE)

Ga-68 DOTATATE​​ has shown improved accuracy for detection relative to indium-111 pentetreotide SPECT-CT ¹​. It binds SSTR subtype 2 and binds 100 times more avidly than indium-111 pentetreotide ².

There are other forms:

These have an affinity for different somatostatin receptors, SSTR subtypes 3 and 5 and SSTR subtype 5, respectively ³.

Physiological high-intensity uptake is typically seen in the spleen ^4,5.

The liver, uncinate process of the pancreas, pituitary gland, adrenal glands and urinary tract typically demonstrates moderate-intensity uptake ^4,5.

The salivary and thyroid glands typically only show mild uptake ^4,5.

In contrast to FDG PET, there is little tracer activity within the brain. 

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6 Recent PET-CT with Gallium 68 (DOTA) Reviews in Turkey: Check Real Patient Experience

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68Ga-DOTATATE PET/CT is the most sensitive exam to detect well-differentiated neuroendocrine tumors. Well-differentiated neuroendocrine tumors do not have an increased sugar metabolism and therefore cannot be detected with 18F-FDG-PET/CT. On the other hand, they have a receptor on the cell surface (SSTR — somatostatin receptor) to which 68Ga-DOTATATE binds and can thus make the tumor visible. This procedure has replaced octreotide scintigraphy in our clinic, as smaller lesions are better detected and can be precisely localized thanks to the combination of PET and CT.

Dotatate PET in oncology

On the axial fused images, a focal DOTATATE multiple accumulation can be localized in the pancreas (red arrow), which corresponds to a small neuroendocrine tumor that could not be delineated by CT. There is also a lymph node metastasis dorsal to the pancreas (yellow arrow).

Indications

• Staging, restaging and recurrence diagnostics of differentiated neuroendocrine tumors (e.g. also before and after 117Lu-DOTATATE therapy).

For details see PDF, page 105ff

Dotatate PET in neurooncology

In the brain, 68Ga-DOTATATE-PET/CT is suitable for clarifying meningiomas and meningioma recurrences, e.g. prior to radiation planning.

High tracer uptake in the meningioma

Indications

• Treatment planning for meningioma

For details see PDF, page 105ff

Responsible doctors

Martin Hüllner, Prof. Dr. med.

Senior Attending Physician, Vice Director of Department, Department of Nuclear Medicine

Research group: Hybrid and molecular tumor imaging, PET/CT and PET/MR, SPECT/CT

Alexander Maurer, Dr. med.

Attending Physician with extended responsibilites, Department of Nuclear Medicine

Multimodal oncological hybrid imaging (PET/CT and PET/MRI), Imaging of prostate cancer (PSMA PET), SPECT/CT

Michael Messerli, PD Dr. med.

Attending Physician with extended responsibilites, Department of Nuclear Medicine

Multimodal oncological imaging, Thoracic imaging, Research group: Hybrid and molecular tumor imaging

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Responsible Department

Introduction

Cancer is a highly unpredictable disease that affects billions of people worldwide. Each type of cancer cell has its own distinct  set of behavioural characteristics. 

What is a DOTA PET scan?

The DOTA PET CT scan (Gallium-68 DOTATATE scan) is a technology available for the detection and care of neuroendocrine tumours (NETs). It is an extremely sensitive technology. The DOTA PET CT scan is able to detect the smallest of lesions quite early. This facilitates a precise and appropriate treatment plan to be set in place for successful treatment response. Unlike other cancers which consume glucose, NETs have receptors for somatostatin, which is a hormone. Hence most of them are not detected on routine imaging techniques such as FDG-PET CT scans. A DOTA PET CT scan is a radioactive scan (68Ga) tagged with DOTATATE that resembles somatostatin and bonds to the tumour receptors to highlight NET. Other previously used cancer imaging techniques which have been in use to diagnose NETs take 4-6 hours and even a few days. In comparison, the DOTA PET CT scan offers higher precision and  accuracy of NET detection. The scan also offers improved patient comfort due to the lesser amount of time which is taken to conduct the scan.

What are the benefits of DOTA PET CT Scans?

The DOTA PET CT scan offers several advantages to doctors and patients. This makes it a very efficient  choice of imaging technology in diagnosing NETs. 

Some of its key benefits include-

1. Faster scanning time– The DOTA PET CT scan can be completed in just 15-20 minutes. This is much quicker than the previous technique of a three-day octreoscan, which takes a minimum of 3-4 days to complete. This allows for timely detection of tumours without the hassle of travelling back and forth to the testing centre consecutively.
2. Detailed images of high quality– The DOTA PET CT scan is highly sensitive. It is able to provide high-resolution images that can identify even sub-centimeter sized lesions. This leads to a higher success rate in the detection of tumours. It also helps doctors to plan appropriate treatments.
3. Assists in creation of treatment plans– The high quality results obtained from a DOTA PET CT scan ensure that doctors and healthcare professionals can effectively and efficiently draw up treatment plans which are appropriate for the patient. They can also use the technology to assess the success of the treatments for the best possible outcome. 

Is a DOTA PET CT scan safe?

Everything in the world has its own set of pros and cons. Likewise, the DOTA PET CT scan also has a few risks that patients should be aware of. They include-

1. Since poorly differentiated NET tumours are less sensitive to show up on a  DOTA PET CT scan, this may make it difficult to identify them at an early stage.
2. Patients taking somatostatin analogs should stop taking the drug for 3-4 weeks before the scan. The drug may show a false negative result on the DOTA PET CT scan.

What do you need to do before a DOTA PET CT scan?

If you are going in for a DOTA PET CT scan, here are a few things you should keep in mind-

• The patient needs to inform the attending nurse, technician or the physician of any previous history of contrast allergy, asthma, arthritis, joint issues or fracture. In such cases, 15 minutes before the procedure, pre-medication is administered.
• The patient must also inform the doctor of any past history of surgery.
• If the patient has done the scan earlier, he should carry the past reports to the diagnostic centre.
• If the patient knows or believes she is pregnant, she should inform the attending staff.

What happens during a DOTA PET CT scan?

Here is what you can expect to happen during the procedure:

• You will be settled comfortably in an area where your privacy is respected throughout the entire procedure. You will also be given a hospital gown to change into.
• You will have to take off all jewellery and ornaments, metallic accessories and inner wear with metal wires etc.
• A cannula is inserted and a small dose of radioactive injection is given via IV. Following this, you will be isolated for 45 minutes to 1 hour. 
• You must drink water during this period of isolation. Before you are taken for the imaging, you will be asked to void urine.
• Post 45 minutes of isolation, the whole body scan is done.
• After this, PET imaging is done. This usually takes about 10 minutes.

Things to keep in mind after a DOTA PET CT Scan

Alright, you went through the main procedure of getting a DOTA PET CT scan. What do you need to do after the procedure? Here are a few things to remember:

• If you were sedated before the scan, you will be kept under observation in the recovery room for some time.
• You must drink at least 2 to 3 litres of water throughout the day. This is essential to flush out the remaining radioactive medicine in the body.
• You should stay away from pregnant women and children for 24 hours to avoid radioactive exposure.
• Lactating mothers should stop feeding for 24 hours after the scan.
• There are no dietary restrictions after the scan.  You may also resume all your normal activities.

ConclusionTo summarise, a DOTA PET CT scan is one of the best techniques available to detect neuroendocrine tumours in the body. The technology helps doctors prepare the right treatment plan for every patient. Visit Kiran PET CT diagnostic centre in Bangalore for your imaging needs and get access to modern healthcare which is designed for your best health.

Федеральное государственное бюджетное учреждение Министерства здравоохранения Российской Федерации
Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина

This information will help you get ready for your positron emission tomography (PET) computed tomography (CT) scan with Dotatate tracer at MSK.

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About your PET-CT with Dotatate tracer

A PET-CT scan is an imaging procedure that is used to:

• Find cancer cells.
• Plan your treatment.
• See how your treatment is working.

You’ll have a CT scan with a low dose of radiation at the same time as your PET scan. CT scans take a fast series of x-ray pictures. The x-ray pictures are combined with your PET scan to create pictures of your soft tissues and bones.

Tracer

Before your PET-CT, you’ll get a radioactive medication called a tracer. The tracer is attached to a substance that your cells and tissues use. Cancer cells use the substance differently than non-cancer cells. The radioactive part of the tracer lets your healthcare provider see how your cells are using the substance. This helps them find any usage that is not normal.

Your PET-CT will use Dotatate as the tracer. You will get the tracer through a catheter (thin, flexible tube). The catheter may be an intravenous (IV) line in your arm, hand, or central venous catheter (CVC), if you have one.

The tracer is used by your cells and doesn’t stay in your body long. It leaves your body mainly through your urine.

Oral contrast

• Iodinated contrast (contrast with iodine).
• Diluted barium sweetened with saccharin.

Both types of contrast work the same way and are used for the same purpose. Both are safe if you have diabetes.

You’ll need to start drinking the oral contrast 45 to 60 minutes before your PET-CT. This will give the contrast solution time to move through your body.

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Getting ready for your PET-CT with Dotatate tracer

Breastfeeding and pregnancy

Take devices off your skin

You may wear certain devices on your skin. Before your scan or procedure, device makers recommend you take off your:

• Continuous glucose monitor (CGM)
• Insulin pump

Talk with your healthcare provider about scheduling your appointment closer to the date you need to change your device. Make sure you have an extra device with you to put on after your scan or procedure.

You may not be sure how to manage your glucose while your device is off. If so, before your appointment, talk with the healthcare provider who manages your diabetes care.

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What to do the day before your PET-CT with Dotatate tracer

If you’re getting anesthesia, read the “For people getting anesthesia” section at the end of this resource.

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What to do the day of your PET-CT with Dotatate tracer

What to expect when you arrive

Many staff members will ask you to say and spell your name and birth date. This is for your safety. People with the same or similar names may be having a procedure on the same day. Once you’re in the department, you’ll fill out a brief questionnaire.

Your care team will inject the tracer  into your vein. You’ll wait about 60 minutes for your body to absorb the tracer. How long this takes will depend on the area of your body being scanned. You will also get contrast to drink at this time.

Try to relax and limit your movement during this time. You can sleep, read, listen to music, or watch videos while you’re waiting. Ask for a blanket if you feel cold.

Your care team will ask you to urinate (pee) just before your scan.

During your PET-CT with Dotatate tracer

When it’s time for your scan, your technologist will bring you to the scanning room. They will help you onto the scanning table. The machine looks like a large doughnut with a hole in the middle (see figure 1). This is the scanning ring (scanner). The scanner is about 3 feet (1 meter) deep.

Once you’re on the scanning table, the table will move slowly through the scanning ring. You must lie very still until your scan is done. This can take 30 to 45 minutes, depending on the type of scan you’re having.

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What to do after your PET-CT with Dotatate tracer

You may leave as soon as your scan is done, unless you have other tests or procedures scheduled. You’ll get a card stating that you had a test done with a radioactive tracer and your test date. Keep this card with you because some security equipment can find radioactivity until it leaves your body. This should take less than a day.

It is safe to be around other people, including pregnant people and children. You can spend time near others, and can kiss, hug, hold, and touch them.

Remember to stay hydrated after your scan. Drink water and other fluids throughout the rest of the day to help remove the tracer from your body. You can go back to your normal diet right away, unless you’re given other instructions.

Instructions for people who are breastfeeding

Stop breastfeeding for 4 hours after your scan. For the time that breastfeeding is interrupted, a mother can still express (pump) milk. She can then either throw away the pumped milk or store it for the same amount of time that breastfeeding is paused before giving it to the baby. During this time, the mother can feed the baby with previously expressed milk or formula.

Your PET-CT results

Back to top For people getting anesthesia

What to do the day before your PET-CT Arrange for someone to take you home You must have a responsible care partner take you home after your procedure. A responsible care partner is someone who can help you get home safely. They should be able to contact your care team if they have any concerns. Make sure to plan this before the day of your procedure. If you don’t have a responsible care partner to take you home, call one of the agencies below. They’ll send someone to go home with you. There’s a charge for this service, and you’ll need to provide transportation. It’s OK to use a taxi or car service, but you still need a responsible care partner with you. Agencies in New York Agencies in New Jersey VNS Health: 888-735-8913 Caring People: 877-227-4649 Caring People: 877-227-4649   Instructions for eating Stop eating at midnight (12 a.m.) the night before your surgery. This includes hard candy and gum. What to do the day of your PET-CT Instructions for drinking Between midnight (12 a.m.) and 2 hours before your arrival time, only drink the liquids on the list below. Do not eat or drink anything else. Stop drinking 2 hours before your arrival time. Water. Clear apple juice, clear grape juice, or clear cranberry juice. Gatorade or Powerade. Black coffee or plain tea. It’s OK to add sugar. Do not add anything else. Do not add any amount of any type of milk or creamer. This includes plant-based milks and creamers. Do not add honey. Do not add flavored syrup. If you have diabetes, pay attention to the amount of sugar in these drinks. It will be easier to control your blood sugar levels if you include sugar-free, low-sugar, or no added sugar versions of these drinks. It’s helpful to stay hydrated before surgery, so drink if you are thirsty. Do not drink more than you need. You will get intravenous (IV) fluids during your surgery. Stop drinking 2 hours before your arrival time. This includes water.

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