Amino Acid PET Imaging of the Early Metabolic Response During Tumor-Treating Fields (TTFields) Therapy in Recurrent Glioblastoma
Authors: Csaba Juhász
Natasha L Robinette
Alit Amit-Yousif
Sharon K Michelhaugh
Sandeep Mittal
Edit Bosnyák
Geoffrey R Barger
Journal: Clinical nuclear medicine (2018)
Discipline: CLINICAL MEDICINE
Keywords: Tumor-treating fields; TTFields therapy; malignant gliomas; amino acid PET; metabolic response

Abstract:  Tumor-treating fields (TTFields) therapy is a relatively new treatment approach for malignant gliomas. We evaluated if amino acid PET can detect an objective metabolic response to TTFields therapy in recurrent glioblastomas. PET scanning with alpha[C-11]-methyl-L-tryptophan (AMT) before and 2 to 3 months after the start of TTFields treatment showed an interval decrease of tryptophan uptake in the whole tumor (2 patients) or in a portion of the tumor (1 patient). These data demonstrate that TTFields therapy can induce an early metabolic response in recurrent glioblastoma, and this treatment response can be detected by amino acid PET. 

Retracted: No

PubPeer comments:
 Alternating electrical field therapy or TTF (tumor-treating-fields) is a new therapeutic modality against primary and recurrent GBM (glioblastoma, a highly aggressive form of brain cancer). Recent reports show TTF extends PFS (progression free survival) and OS (overall survival) in this cohort of patients that had a previous median survival of 16 months despite surgery, chemo and radiotherapy. https: en.wikipedia.org wiki Alternating_electric_field_therapy This paper reports on 3 patients. The issue is not TTF therapy, but the imaging modality. It is routine to use FDG-PET (18F-labeled deoxyglucose; images high glucose catabolism - Warburg effect) to image and stage GBM. These neurosurgeons use AMT-PET (alpha-methyl-tryptophan; images tryptophan catabolism) to image the tumors pre- and post TTF treatment. The problem? AMT is a known irreversible allosteric activator of a major immunosuppresive pathway of aggressive tumors (diagram). Positive feedback loops can trigger and maintain immunesuppression when AMT is administered. In otherwords, AMT in AMT-PET likely makes the tumors more aggressive. https: www.ncbi.nlm.nih.gov pubmed 5367800 Studies on the allosteric regulation of tryptophan oxygenase structure and function. by Feigelson P. https: www.ncbi.nlm.nih.gov pubmed 5575299 Alpha-methyltryptophan and its actions on tryptophan metabolism. by Sourkes TL. https: en.wikipedia.org wiki Indoleamine_2,3-dioxygenase Doctors, aren t you placing the patients in harm s way by using AMT-PET? Switch to FDG-PET, and you may get better PFS and OS in your clinical trial. Your imaging vs. treatment strategy appears to have as much logic as feeding corn-syrup to diabetic patients in-between their insulin shots. Think!!! ![file] ![file] , 
 AMT-PET is very beneficial to glioblastoma brain cancer patients. Professor Sandeep Mittal and Professor Csaba Juhasz pioneered AMT-PET clinical studies at Wayne State Medical School and Detroit Medical Centre, supported by assorted neurologists and radiologists and researchers. See their excellent review about AMT-PET. https: www.ncbi.nlm.nih.gov pubmed ?term=24825818 AMT-PET is far, far superior to FDG-PET, 1. to image, 2. to stage, 3. to evaluate glioblastoma.See scans below for evidence. Glioblastomas (GBM) have very high active kynurenine pathway anyways. AMT is a superb PET tracer to follow kynurenine pathway because AMT is consumed by IDO enzyme and get trapped in GBM cells. Glucose pathway is high in regular brain. Because of this FDG-PET in not able to contrast better. AMT is far, far superior. Many glioblastoma patients had the AMT-PET scans, and helped them live longer because neurosurgeons can image glioblastoma with very high contrast. Previous person said AMT allosteric activation of IDO can be harmful to patient. IDO is very high expressed in glioblastoma anyways. Because of this any activation of IDO by AMT is immaterial. Taking pros and cons of AMT, cons are negligible compared to pros. ![file] , 
 I had a good look at those  superb AMT-PET scans. Indeed, they are superb. I shall say, in fact those are extraordinary! ![file] Why do I say that? It is not possible to paint the Kynurenine pathway with AMT (alphamethyl-tryptophan) because AMT is not a substrate of IDO, the enzyme at top of the said pathway. If AMT cannot enter the pathway, it cannot paint the pathway in a PET scan. Reference: Sourkes TL. Alpha-methyltryptophan and its actions on tryptophan metabolism. Fed Proc. 1971 May-Jun; 30 (3): 897-903. PMID: 5575299 https: www.ncbi.nlm.nih.gov pubmed 5575299 I invite the authors to explain their PET scans. You have achieved an extraordinary feat that defeats biochemistry! ![file] ,