Maximizing the use of batch production of 18F-FDOPA for imaging of brain tumors to increase availability of hybrid PET/MR imaging in clinical setting

Abstract Background Amino acid PET imaging of brain tumors has been shown to play an important role in predicting tumor grade, delineation of tumor margins, and differentiating tumor recurrence from the background of post-radiation changes, but is not commonly used in clinical practice due to high cost. We propose that PET/MRI imaging of patients grouped to the day of tracer radiosynthesis will significantly decrease the cost of PET imaging, which will improve patient access to PET. Methods Seventeen patients with either primary brain tumors or metastatic brain tumors were recruited for imaging on 3T PET/MRI and were scanned on 4 separate days in groups of 3-5 patients. The first group of consecutively imaged patients contained three patients, followed by two groups of 5 patients, and last group of 4 patients. Results For each of the patients, standard of care gadolinium enhanced MRI and dynamic PET imaging with 18F-FDOPA amino acid tracer was obtained. The total cost savings of scanning 17 patients in batches of 4 as opposed to individual radiosynthesis was 48.5% ($28,321). Semiquantitative analysis of tracer uptake in normal brain were performed with appropriate accumulation and expected subsequent washout. Conclusion Amino acid PET tracers have been shown to play a critical role in characterization of brain tumors but their adaptation to clinical practice has been limited due to high cost of PET. Scheduling patient imaging to maximally utilize the radiosynthesis of imaging tracer significantly reduces the cost of PET and results in increased availability of PET tracer use in neuro-oncology.

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18F-FACBC PET/MRI in the evaluation of human brain metastases: a case report

European Journal of Hybrid Imaging ◽

10.1186/s41824-021-00101-6 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Knut Johannessen ◽

Erik Magnus Berntsen ◽

Håkon Johansen ◽

Tora S. Solheim ◽

Anna Karlberg ◽

...

Keyword(s):

Case Report ◽

Clinical Practice ◽

Amino Acid ◽

Brain Metastases ◽

Metastatic Cancer ◽

Low Grade ◽

Pet Tracer ◽

Before And After ◽

Amino Acid Pet ◽

And Function

Abstract Background Patients with metastatic cancer to the brain have a poor prognosis. In clinical practice, MRI is used to delineate, diagnose and plan treatment of brain metastases. However, MRI alone is limited in detecting micro-metastases, delineating lesions and discriminating progression from pseudo-progression. Combined PET/MRI utilises superior soft tissue images from MRI and metabolic data from PET to evaluate tumour structure and function. The amino acid PET tracer 18F-FACBC has shown promising results in discriminating high- and low-grade gliomas, but there are currently no reports on its use on brain metastases. This is the first study to evaluate the use of 18F-FACBC on brain metastases. Case presentation A middle-aged female patient with brain metastases was evaluated using hybrid PET/MRI with 18F-FACBC before and after stereotactic radiotherapy, and at suspicion of recurrence. Static/dynamic PET and contrast-enhanced T1 MRI data were acquired and analysed. This case report includes the analysis of four 18F-FACBC PET/MRI examinations, investigating their utility in evaluating functional and structural metastasis properties. Conclusion Analysis showed high tumour-to-background ratios in brain metastases compared to other amino acid PET tracers, including high uptake in a very small cerebellar metastasis, suggesting that 18F-FACBC PET can provide early detection of otherwise overlooked metastases. Further studies to determine a threshold for 18F-FACBC brain tumour boundaries and explore its utility in clinical practice should be performed.

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CBMT-03. EVALUATION OF PET TRACERS TO DIFFERENTIATE IDH1 MUTANT GBM

Neuro-Oncology ◽

10.1093/neuonc/noz175.125 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi33-vi33

Author(s):

Andrei Molotkov ◽

Angeliki Mela ◽

Peter D Canoll ◽

Akiva Mintz

Keyword(s):

Amino Acid ◽

Pet Imaging ◽

Causal Link ◽

Amino Acid Derivative ◽

Normal Brain ◽

Pet Tracers ◽

Pet Tracer ◽

Altered Glucose ◽

Pet Ct ◽

18F Fdg

Abstract OBJECTIVE PET/CT offers the unique potential to noninvasively evaluate biomarker expression and aberrant metabolism. 18F-FDG has driven PET/CT to the forefront of cancer imaging, as altered glucose metabolism is a hallmark of oncogenesis. However, 18F-FDG is suboptimal for GBM due to high physiologic uptake in normal brain. The development of alternative tracers has reignited the field of PET/CT in GBM and offers hope for diagnosis and molecular staging in GBM. We hypothesize that fundamental differences in metabolism and oncogene expression present in IDH1 mutatant gliomas can be shown using PET imaging, as has been suggested in some correlative clinical studies. Our objective was therefore to establish a causal link between IDH1 mutation in GBM and uptake of targeted PET tracers in a unique proneural GBM transgenic model characterized by p53, IDH1 mutations and PDGF expression. METHODS We examined the uptake of 3 blood-brain-barrier (BBB) penetrant tracers that have been used in GBM: (a) 18F-FDG, a surrogate for increased glycolysis; (b) 18F-Fluciclovine, an amino acid derivative transported into cells through the energy-independent L-type amino acid transporter (LAT) system and is approved by the FDA for prostate cancer; and (c) 11C-ER176, a tracer that binds the TSPO receptor that is generally expressed on activated microglia as well as GBM. RESULTS We did not observe significant differences in 18F-FDG uptake between wt and IDH mutant GBM cells. However, we found that IDH mutant GBM cells demonstrated significantly increased 18F-Fluciclovine (47%) and 11C-ER176 (53%) versus IDH wt cells. CONCLUSION We have established a causal link between IDH mutation status and uptake of (a) 18F-Fluciclovine, a promising FDA approved PET tracer and (b) 11C-ER176, a second generation TSPO ligand. Thus, we are performing further studies in orthotopic syngeneic GBM models to determine if PET imaging can non-invasively demonstrate molecular characterization and therapeutic stratification in glioma.

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Radiolabeled, non-natural amino acid PET imaging of brain tumors

Science-Business eXchange ◽

10.1038/scibx.2010.1108 ◽

2010 ◽

Vol 3 (36) ◽

pp. 1108-1108

Keyword(s):

Amino Acid ◽

Brain Tumors ◽

Pet Imaging ◽

Natural Amino Acid ◽

Amino Acid Pet

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Kinetic Analysis of 2-[11C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Compartmental Model Investigation and Mathematical Analysis

Molecular Imaging ◽

10.1162/15353500200202112 ◽

2002 ◽

Vol 1 (3) ◽

pp. 153535002002021

Author(s):

Joanne M. Wells ◽

David A. Mankoff ◽

Mark Muzi ◽

Finbarr O'Sullivan ◽

Janet F. Eary ◽

...

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Cellular Proliferation ◽

Compartment Model ◽

Response To Therapy ◽

Model Parameters ◽

Normal Brain ◽

Identifiability Analysis ◽

Pet Tracer ◽

Thymidine Transport

2-[11C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. We previously described and validated a five-compartment model for thymidine incorporation into DNA in somatic tissues, but the effect of the blood–brain barrier on the transport of TdR and its metabolites necessitated further validation before it could be applied to brain tumors. Methods: We investigated the behavior of the model under conditions experienced in the normal brain and brain tumors, performed sensitivity and identifiability analysis to determine the ability of the model to estimate the model parameters, and conducted simulations to determine whether it can distinguish between thymidine transport and retention. Results: Sensitivity and identifiability analysis suggested that the non-CO2 metabolite parameters could be fixed without significantly affecting thymidine parameter estimation. Simulations showed that K1t and KTdR could be estimated accurately ( r = .97 and .98 for estimated vs. true parameters) with standard errors < 15%. The model was able to separate increased transport from increased retention associated with tumor proliferation. Conclusion: Our model adequately describes normal brain and brain tumor kinetics for thymidine and its metabolites, and it can provide an estimate of the rate of cellular proliferation in brain tumors.

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Comparison of Amino Acid PET to Advanced and Emerging MRI Techniques for Neurooncology Imaging: A Systematic Review of the Recent Studies

Molecular Imaging ◽

10.1155/2021/8874078 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Brittany M. Stopa ◽

Csaba Juhász ◽

Sandeep Mittal

Keyword(s):

Systematic Review ◽

Amino Acid ◽

Brain Tumors ◽

Tumor Imaging ◽

Imaging Techniques ◽

Diagnostic Potential ◽

Cest Imaging ◽

Pubmed Search ◽

Amino Acid Pet ◽

Improved Performance

Introduction. Standard neuroimaging protocols for brain tumors have well-known limitations. The clinical use of additional modalities including amino acid PET (aaPET) and advanced MRI (aMRI) techniques (including DWI, PWI, and MRS) is emerging in response to the need for more accurate detection of brain tumors. In this systematic review of the past 2 years of the literature, we discuss the most recent studies that directly compare or combine aaPET and aMRI for brain tumor imaging. Methods. A PubMed search was conducted for human studies incorporating both aaPET and aMRI and published between July 2018 and August 2020. Results. A total of 22 studies were found in the study period. Recent studies of aaPET with DWI showed a superiority of MET, FET, FDOPA, and AMT PET for detecting tumor, predicting recurrence, diagnosing progression, and predicting survival. Combining modalities further improved performance. Comparisons of aaPET with PWI showed mixed results about spatial correlation. However, both modalities were able to detect high-grade tumors, identify tumor recurrence, differentiate recurrence from treatment effects, and predict survival. aaPET performed better on these measures than PWI, but when combined, they had the strongest results. Studies of aaPET with MRS demonstrated that both modalities have diagnostic potential but MET PET and FDOPA PET performed better than MRS. MRS suffered from some data quality issues that limited analysis in two studies, and, in one study that combined modalities, overall performance actually decreased. Four recent studies compared aaPET with emerging MRI approaches (such as CEST imaging, MR fingerprinting, and SISTINA), but the initial results remain inconclusive. Conclusions. aaPET outperformed the aMRI imaging techniques in most recent studies. DWI and PWI added meaningful complementary data, and the combination of aaPET with aMRI yielded the best results in most studies.

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Amino Acid PET Imaging of the Early Metabolic Response During Tumor-Treating Fields (TTFields) Therapy in Recurrent Glioblastoma

Clinical Nuclear Medicine ◽

10.1097/rlu.0000000000001942 ◽

2018 ◽

Vol 43 (3) ◽

pp. 176-179 ◽

Cited By ~ 6

Author(s):

Edit Bosnyák ◽

Geoffrey R. Barger ◽

Sharon K. Michelhaugh ◽

Natasha L. Robinette ◽

Alit Amit-Yousif ◽

...

Keyword(s):

Amino Acid ◽

Pet Imaging ◽

Metabolic Response ◽

Recurrent Glioblastoma ◽

Tumor Treating Fields ◽

Amino Acid Pet ◽

Early Metabolic Response

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Role of Amino Acid PET Tracers in Pediatric Brain Tumors

Atlas of PET/CT in Pediatric Patients ◽

10.1007/978-88-470-5358-8_19 ◽

2013 ◽

pp. 157-163 ◽

Cited By ~ 1

Author(s):

Arnoldo Piccardo ◽

Giovanni Morana

Keyword(s):

Amino Acid ◽

Brain Tumors ◽

Pediatric Brain Tumors ◽

Pet Tracers ◽

Amino Acid Pet ◽

Pediatric Brain

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Kinetic Analysis of 2-[11C]Thymidine PET Imaging Studies of Malignant Brain Tumors: Preliminary Patient Results

Molecular Imaging ◽

10.1162/15353500200202115 ◽

2002 ◽

Vol 1 (3) ◽

pp. 153535002002021

Author(s):

Joanne M. Wells ◽

David A. Mankoff ◽

Janet F. Eary ◽

Alexander M. Spence ◽

Mark Muzi ◽

...

Keyword(s):

Brain Tumors ◽

Kinetic Analysis ◽

Cellular Proliferation ◽

Response To Therapy ◽

Response To Treatment ◽

Normal Brain ◽

Arterial Blood ◽

Pet Tracer ◽

Wide Range ◽

Thymidine Transport

2-[11C]Thymidine (TdR), a PET tracer for cellular proliferation, may be advantageous for monitoring brain tumor progression and response to therapy. Kinetic analysis of dynamic TdR images was performed to estimate the rate of thymidine transport ( K1t) and thymidine flux ( KTdR) into brain tumors and normal brain. These estimates were compared to MRI and pathologic results. Methods: Twenty patients underwent sequential [11C]CO2 (major TdR metabolite) and TdR PET studies with arterial blood sampling and metabolite analysis. The data were fitted using the five-compartment model described in the companion article. Results: Comparison of model estimates with clinical and pathologic data shows that K1t is higher for MRI contrast enhancing tumors ( p > .001), and KTdR increases with tumor grade ( p > .02). On average, TdR retention was lower after treatment in high-grade tumors. The model was able to distinguish between increased thymidine transport due to blood–brain barrier breakdown and increased tracer retention associated with tumor cell proliferation. Conclusion: Initial analysis of model estimates of thymidine retention and transport show good agreement with the clinical and pathological features of a wide range of brain tumors. Ongoing studies will evaluate its role in measuring response to treatment and predicting outcome.

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