Pharmacokinetics of [18F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer’s disease

Purpose

The aim of this study was to investigate the potential of [¹⁸F]flutemetamol as a preclinical PET tracer for imaging β-amyloid (Aβ) deposition by comparing its pharmacokinetics to those of [¹¹C]Pittsburgh compound B ([¹¹C]PIB) in wild-type Sprague Dawley rats and C57Bl/6N mice. In addition, binding of [¹⁸F]flutemetamol to Aβ deposits was studied in the Tg2576 transgenic mouse model of Alzheimer’s disease.

Methods

[¹⁸F]Flutemetamol biodistribution was evaluated using ex vivo PET methods and in vivo PET imaging in wild-type rats and mice. Metabolism and binding of [¹¹C]PIB and [¹⁸F]flutemetamol to plasma proteins were analysed using thin-layer chromatography and ultrafiltration methods, respectively. Radiation dose estimates were calculated from rat ex vivo biodistribution data. The binding of [¹⁸F]flutemetamol to Aβ deposits was also studied using ex vivo and in vitro autoradiography. The location of Aβ deposits in the brain was determined with thioflavine S staining and immunohistochemistry.

Results

The pharmacokinetics of [¹⁸F]flutemetamol resembled that of [¹¹C]PIB in rats and mice. In vivo studies showed that both tracers readily entered the brain, and were excreted via the hepatobiliary pathway in both rats and mice. The metabolism of [¹⁸F]flutemetamol into radioactive metabolites was faster than that of [¹¹C]PIB. [¹⁸F]Flutemetamol cleared more slowly from the brain than [¹¹C]PIB, particularly from white matter, in line with its higher lipophilicity. Effective dose estimates for [¹¹C]PIB and [¹⁸F]flutemetamol were 2.28 and 6.65?μSv/MBq, respectively. Autoradiographs showed [¹⁸F]flutemetamol binding to fibrillar Aβ deposits in the brain of Tg2576 mice.

Conclusion

Based on its pharmacokinetic profile, [¹⁸F]flutemetamol showed potential as a PET tracer for preclinical imaging. It showed good brain uptake and was bound to Aβ deposits in the brain of Tg2576 mice. However, its high lipophilicity might complicate the analysis of PET data, particularly in small-animal imaging.     

[18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer’s disease

Purpose

The aim was to identify the amyloid beta (Aβ) deposition by positron emission tomography (PET) imaging with the ¹⁸F-labeled Pittsburgh compound B (PIB) derivative [¹⁸F]flutemetamol (FMM) across a spectrum of Alzheimer’s disease (AD) and to compare Aβ deposition between [¹⁸F]FMM and [¹¹C]PIB PET imaging.

Methods

The study included 36 patients with AD, 68 subjects with mild cognitive impairment (MCI), 41 older healthy controls (HC) (aged ≥56), 11 young HC (aged ≤45), and 10 transitional HC (aged 46–55). All 166 subjects underwent 30-min static [¹⁸F]FMM PET 85 min after injection, 60-min dynamic [¹¹C]PIB PET, and cognitive testing. [¹⁸F]FMM scans were assessed visually, and standardized uptake value ratios (SUVR) were defined quantitatively in regions of interest identified on coregistered MRI (cerebellar cortex as a reference region). The PIB distribution volume ratios (DVR) were determined in the same regions.

Results

Of 36 AD patients, 35 had positive scans, while 36 of 41 older HC subjects had negative scans. [¹⁸F]FMM scans had a sensitivity of 97.2 % and specificity of 85.3 % in distinguishing AD patients from older HC subjects, and a specificity of 100 % for young and transitional HC subjects. The [¹¹C]PIB scan had the same results. Interreader agreement was excellent (kappa score?=?0.81). The cortical FMM SUVR in AD patients was significantly greater than in older HC subjects (1.76?±?0.23 vs 1.30?±?0.26, p?<?0.01). Of the MCI patients, 68 had a bimodal distribution of SUVR, and 29 of them (42.6 %) had positive scans. Cortical FMM SUVR values were strongly correlated with PIB DVR (r?=?0.94, n?=?145, p?<?0.001).

Conclusion

[¹⁸F]FMM PET imaging detects Aβ deposition in patients along the continuum from normal cognitive status to dementia of AD and discriminates AD patients from HC subjects, similar to [¹¹C]PIB PET.     

In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer’s disease patients

Purpose

Imaging the 18-kDa translocator protein (TSPO) is considered a potential tool for in vivo evaluation of microglial activation and neuroinflammation in the early stages of Alzheimer’s disease (AD). ((R)-1-(2-chlorophenyl)-N-[¹¹C]-methyl-N-(1-methylpropyl)-3-isoquinoline caboxamide ([¹¹C]-(R)-PK11195) has been widely used for PET imaging of TSPO and, despite its low specific-to-nondisplaceable binding ratio, increased TSPO binding has been shown in AD patients. The high-affinity radioligand N-(5-fluoro-2-phenoxyphenyl)-N-(2-[¹⁸F]fluoroethyl-5-methoxybenzyl)acetamide ([¹⁸F]FEDAA1106) has been developed as a potential in vivo imaging tool for better quantification of TSPO binding. The aim of this study was to quantify in vivo binding of [¹⁸F]FEDAA1106 to TSPO in control subjects and AD patients.

Methods

Seven controls (five men, two women, age 68±3 years, MMSE score 29±1) and nine AD patients (six men, three women, age 69±4 years, MMSE score 25±3) were studied with [¹⁸F]FEDAA1106. PET measurements were performed on an ECAT EXACT HR system (Siemens Medical Solutions) in two 60-min dynamic PET sessions with a 30-min interval between sessions. Arterial blood radioactivity was measured using an automated blood sampling system for the first 5 min and using manually drawn samples thereafter. Quantification was performed using both kinetic analysis based on a two-tissue compartment model and Logan graphical analysis. Outcome measures were total distribution volume (V _T) and binding potential (BP _ND=k ₃/k ₄). An estimate of nondisplaceable distribution volume was obtained with the Logan graphical analysis using the first 15 min of PET measurements (V _{ND 1-15 min}). Binding potential (BP _ND) was also calculated as: V _T/V _{ND 1-15 min} ? 1.

Results

No statistically significant differences in V _T, k ₃/k ₄ or BP _ND were observed between controls and AD patients.

Conclusion

This study suggests that TSPO imaging with [¹⁸F]FEDAA1106 does not enable the detection of microglial activation in AD.     

Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

Purpose

Amyloid imaging with ¹⁸F-labelled radiotracers will allow widespread use of this technique, facilitating research, diagnosis and therapeutic development for Alzheimer’s disease (AD). The purpose of this analysis was to compare data on cortical Aβ deposition in subjects who had undergone both ¹¹C-PiB (PiB) and ¹⁸F-florbetaben (FBB) PET imaging.

Methods

We identified ten healthy elderly controls (HC) and ten patients with AD who had undergone PET imaging after intravenous injection of 370?MBq of PiB and 300?MBq of FBB under separate research protocols. PiB and FBB images were coregistered so that placement of regions of interest was identical on both scans and standard uptake value ratios (SUVR) using the cerebellar cortex as reference region were calculated between 40 and 70?min and between 90 and 110?min after injection for PiB and FBB, respectively.

Results

Significantly higher SUVR values (p?r?=?0.97, p?d 3.3 for PiB and 3.0 for FBB).

Conclusion

FBB, while having a narrower dynamic range than PiB, clearly distinguished HC from AD patients, with a comparable effect size. FBB seems a suitable ¹⁸F radiotracer for imaging AD pathology in vivo.     

A European multicentre PET study of fibrillar amyloid in Alzheimer��s disease

Purpose

Amyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer??s disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies.

Methods

In this study 238 [¹¹C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [¹¹C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69?±?8?years), 72 patients with mild cognitive impairment (MCI; mean age 67.5?±?8?years) and 51 healthy controls (mean age 67.4?±?6?years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28?±?15?months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype.

Results

[¹¹C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [¹¹C]PIB retention was observed in MCI patients, with a bimodal distribution (64?% MCI PIB-positive and 36?% MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [¹¹C]PIB retention was observed in MCI ApoE ??4 carriers compared to non-ApoE ??4 carriers (p?<?0.005). Of the MCI PIB-positive patients, 67?% had converted to AD at follow-up while none of the MCI PIB-negative patients converted.

Conclusion

This study demonstrated the robustness of [¹¹C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25?% per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100?% negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.     

The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer’s disease

Purpose

The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer’s disease (AD) patients and healthy elderly controls.

Methods

Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [¹¹C]PIB to assess amyloid-β plaque load and [¹⁸F]FDG to assess glucose metabolism. [¹¹C]PIB binding and [¹⁸F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD.

Results

While amyloid-β plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho?=?0.56, p?<?0.05).

Conclusion

The present study shows that in a group of AD patients amyloid-β plaque load as measured by [¹¹C]PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [¹⁸F]FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration.     

Cerebrospinal fluid lactate levels and brain [18F]FDG PET hypometabolism within the default mode network in Alzheimer’s disease

Purpose

It has been suggested that neuronal energy metabolism may be involved in Alzheimer’s disease (AD). In this view, the finding of increased cerebrospinal fluid (CSF) lactate levels in AD patients has been considered the result of energetic metabolism dysfunction. Here, we investigated the relationship between neuronal energy metabolism, as measured via CSF lactate levels, and cerebral glucose metabolism, as stated at the 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ([18F]FDG PET) in AD patients.

Methods

AD patients underwent lumbar puncture to measure CSF lactate levels and [18F]FDG PET to assess brain glucose metabolism. CSF and PET data were compared to controls. Since patients were studied at rest, we specifically investigated brain areas active in rest-condition owing to the Default Mode Network (DMN). We correlated the CSF lactate concentrations with the [18F]FDG PET data in brain areas owing to the DMN, using sex, age, disease duration, Mini Mental State Examination, and CSF levels of tau proteins and beta-amyloid as covariates.

Results

AD patients (n?=?32) showed a significant increase of CSF lactate levels compared to Control 1 group (n?=?28). They also showed brain glucose hypometabolism in the DMN areas compared to Control 2 group (n?=?30). Within the AD group we found the significant correlation between increased CSF lactate levels and glucose hypometabolism in Broadman areas (BA) owing to left medial prefrontal cortex (BA10, mPFC), left orbitofrontal cortex (BA11, OFC), and left parahippocampal gyrus (BA 35, PHG).

Conclusion

We found high CSF levels of lactate and glucose hypometabolism within the DMN in AD patients. Moreover, we found a relationship linking the increased CSF lactate and the reduced glucose consumption in the left mPFC, OFC and PHG, owing to the anterior hub of DMN. These findings could suggest that neural glucose hypometabolism may affect the DMN efficiency in AD, also proposing the possible role of damaged brain energetic machine in impairing DMN.

     

Comparison of the diagnostic performance of FDG-PET and VBM-MRI in very mild Alzheimer’s disease

Purpose The aim of this study was to compare the diagnostic performance of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM) on magnetic resonance imaging (MRI) in the same group of patients with very mild Alzheimer’s disease (AD). Methods Thirty patients with very mild AD (age 67.0±5.8 years; MMSE score 25.5±1.2, range 24–28), 32 patients with mild AD (age 67.0±4.5 years, MMSE score 22.1±0.8, range 21–23) and 60 age- and sex-matched normal volunteers underwent both FDG-PET and three-dimensional spoiled gradient echo MRI. Statistical parametric mapping was used to conduct voxel by voxel analysis and Z score mapping. First, the region of interest (ROI) maps of significant reductions in glucose metabolism and grey matter density in the mild AD patients were defined. Secondly, analysis of receiver operating characteristic (ROC) curves for Z scores in the ROI maps discriminating very mild AD patients and normal controls was performed. Results In mild AD patients, FDG-PET indicated significant reductions in glucose metabolism in the bilateral posterior cingulate gyri and the right parietotemporal area, while VBM analysis showed a significant decrease in grey matter volume density in the bilateral amygdala/hippocampus complex, compared with the normal control group. ROC analysis showed that in very mild AD patients the accuracy of FDG-PET diagnosis was 89% and that of VBM-MRI diagnosis was 83%. The accuracy of the combination of FDG-PET and VBM-MRI diagnosis was 94%. Conclusion In very mild AD, both FDG-PET and VBM-MRI had high accuracy for diagnosis, but FDG-PET showed slightly higher accuracy than VBM-MRI. Combination of the two techniques will yield a higher diagnostic accuracy in very mild AD by making full use of functional and morphological images.     

Comparison of [18 F]FDG PET/CT and MRI in the diagnosis of active osteomyelitis

Objective

In diagnosing osteomyelitis (OM) both MRI and [18 F]FDG PET-CT proved to be accurate modalities. In anticipation of the advent of hybrid PET/MRI scanners we analyzed our patient group to give direction to future imaging strategies in patients with suspected OM.

Materials and methods

In this retrospective study all patients of a tertiary referral center who underwent both an MRI and a PET for the diagnosis of OM were included. The results of those scans were evaluated using patient’s histology, microbiological findings, and clinical/radiological follow-up. Additionally, ROC curve analysis of the SUVmax and the SUVmax ratio on the PET scans was performed. Two imaging strategies were simulated: first MRI followed by PET, or vice versa.

Results

Twenty-seven localizations in 26 patients were included. Both MRI and PET were shown to be accurate in our patients for the qualitative detection of OM. A cut-off value for the SUVmax of 3 gave optimal results (a specificity of 90 % with a sensitivity of 88 %). The SUVmax ratio gave a worse performance. The two simulated imaging strategies showed no difference in the final diagnosis in 20 out of 27 cases. Remarkably, 6 equivocal cases were all correctly diagnosed by the second modality, i.e., PET or MRI.

Conclusion

Both MRI and [18 F]FDG PET were accurate in diagnosing OM in a tertiary referral hospital population. Simulation of imaging strategies showed that a combined sequential strategy was optimal. It seems preferable to use MRI as a primary imaging tool for uncomplicated unifocal cases, whereas in cases with (possible) multifocal disease or a contraindication for MRI, PET is preferred. This combined sequential strategy looks promising, but needs to be confirmed in a larger prospective study.     

Dosimetry and efficacy of a tau PET tracer [18F]MK-6240 in Japanese healthy elderly and patients with Alzheimer’s disease

Annals of Nuclear Medicine - A new tau PET tracer [18F]MK-6240 has been developed; however, its dosimetry and pharmacokinetics have been published only for a European population. This study...     

Detection of amyloid in Alzheimer’s disease with positron emission tomography using [11C]AZD2184

Purpose

Current positron emission tomography (PET) radioligands for detection of Aβ amyloid in Alzheimer’s disease (AD) are not ideal for quantification. To improve the signal to noise ratio we have developed the radioligand [¹¹C]AZD2184 and report here the first clinical evaluation.

Methods

Eight AD patients and four younger control subjects underwent 93-min PET measurements with [¹¹C]AZD2184. A ratio approach using the cerebellum as reference region was applied to determine binding parameters.

Results

Brain uptake of [¹¹C]AZD2184 peaked within 1 min at 3–4% of injected radioactivity. AD patients had high radioactivity in cortical regions while controls had uniformly low radioactivity uptake. Specific binding peaked within 30 min at which time standardized uptake value ratios (SUVR) ranged between 1.19 and 2.57.

Conclusion

[¹¹C]AZD2184 is a promising radioligand for detailed mapping of Aβ amyloid depositions in Alzheimer’s disease, due to low non-specific binding, high signal to background ratio and reversible binding as evident from early peak equilibrium.     

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent — a pilot study

PurposeThe compound (E)-4-(2-(6-(2-(2-(2-¹⁸F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([¹⁸F]AV-45) is a novel radiopharmaceutical capable of selectively binding to β-amyloid (Aβ) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [¹⁸F]AV-45 in human subjects.MethodsIn vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0±5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9±13.9 MBq of [¹⁸F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7±13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information.ResultsIn vitro autoradiography revealed exquisitely high specific binding of [¹⁸F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12±0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7±78.6 μGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [¹⁸F]AV-45 were 33.8±3.4 μSv/MBq and 19.3±1.3 μSv/MBq, respectively.Conclusion[¹⁸F]AV-45 binds specifically to Aβ in vitro, and is a safe PET tracer for studying Aβ distribution in human brain. The dosimetry is suitable for clinical and research application.     

Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer’s disease patients

Purpose

The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer’s disease (AD).

Methods

In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [¹¹C]AZD2995 and [¹¹C]AZD2184 in three healthy control subjects and seven AD patients.

Results

AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [³H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [¹¹C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [¹¹C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus.

Conclusion

Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [¹¹C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [¹¹C]AZD2995. However, the very low nonspecific binding of [¹¹C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy.     

Evaluation of metabolism,plasma protein binding and other biological parameters after administration of (−)-[18 F]Flubatine in humans

Introduction(−)-[¹⁸ F]Flubatine is a PET tracer with high affinity and selectivity for the nicotinic acetylcholine α₄β₂ receptor subtype. A clinical trial assessing the availability of this subtype of nAChRs was performed. From a total participant number of 21 Alzheimer’s disease (AD) patients and 20 healthy controls (HCs), the following parameters were determined: plasma protein binding, metabolism and activity distribution between plasma and whole blood.MethodsPlasma protein binding and fraction of unchanged parent compound were assessed by ultracentrifugation and HPLC, respectively. The distribution of radioactivity (parent compound + metabolites) between plasma and whole blood was determined ex vivo at different time-points after injection by gamma counting after separation of whole blood by centrifugation into the cellular and non-cellular components. In additional experiments in vitro, tracer distribution between these blood components was assessed for up to 90 min.ResultsA fraction of 15% ± 2% of (−)-[¹⁸ F]Flubatine was found to be bound to plasma proteins. Metabolic degradation of (−)-[¹⁸ F]Flubatine was very low, resulting in almost 90% unchanged parent compound at 90 min p.i. with no significant difference between AD and HC. The radioactivity distribution between plasma and whole blood changed in vivo only slightly over time from 0.82 ± 0.03 at 3 min p.i. to 0.87 ± 0.03 at 270 min p.i. indicating the contribution of only a small amount of metabolites. In vitro studies revealed that (−)-[¹⁸ F]Flubatine was instantaneously distributed between cellular and non-cellular blood parts.Discussion(−)-[¹⁸ F]Flubatine exhibits very favourable characteristics for a PET radiotracer such as slow metabolic degradation and moderate plasma protein binding. Equilibrium of radioactivity distribution between plasma and whole blood is reached instantaneously and remains almost constant over time allowing both convenient sample handling and facilitated fractional blood volume contribution assessment.     

[18F]FLT-PET to predict pharmacodynamic and clinical response to cetuximab therapy in Ménétrier’s disease

Molecular imaging biomarkers of proliferation hold great promise for quantifying response to personalized medicine. One such approach utilizes the positron emission tomography (PET) tracer 3??-deoxy-3??[¹⁸F]-fluorothymidine ([¹⁸F]FLT), an investigational agent whose uptake reflects thymidine salvage-dependent DNA synthesis. The goal of this study was to evaluate [¹⁸F]FLT-PET in the setting of Ménétrier??s disease (MD), a rare, premalignant hyperproliferative disorder of the stomach treatable with cetuximab therapy. Over 15?months, a patient with confirmed MD underwent cetuximab therapy and was followed with sequential [¹⁸F]FLT-PET. For comparison to MD, an [¹⁸F]FLT-PET study was conducted in another patient to quantify uptake in a normal stomach. Prior to cetuximab therapy, stomach tissue in MD was easily visualized with [¹⁸F]FLT-PET, with pre-treatment uptake levels exceeding normal stomach uptake by approximately fourfold. Diminished [¹⁸F]FLT-PET in MD was observed following the initial and subsequent doses of cetuximab and correlated with clinical resolution of the disease. To our knowledge, this study reports the first clinical use of [¹⁸F]FLT-PET to assess proliferation in a premalignant disorder. We illustrate that the extent of MD involvement throughout the stomach could be easily visualized using [¹⁸F]FLT-PET, and that response to cetuximab could be followed quantitatively and non-invasively in sequential [¹⁸F]FLT-PET studies. Thus, [¹⁸F]FLT-PET appears to have potential to monitor response to treatment in this and potentially other hyperproliferative disorders.