Adriaan Lammertsma

• Amsterdam University Medical Center

Permeability‐glycoprotein (P‐gp), a crucial efflux pump transporter encoded by the ABCB1 gene, plays a pivotal role in drug disposition at the blood–brain barrier (BBB) and is involved in the pharmacokinetics of numerous therapeutic agents. This study investigates differences in P‐gp function at the BBB between males and females in a cohort of olde...

Background/Objectives: The complex pathophysiology of painful cervical radiculopathy is only partially understood. Neuroimmune activation in the dorsal root ganglion and spinal cord is assumed to underlie the genesis of radicular pain. Molecular positron emission tomography (PET) using the radiotracer [¹¹C]DPA713, which targets the 18-kDa transloca...

This single case study examines selective Pittsburgh compound-B (PiB) binding to an intracerebral light-chain amyloidoma using a 90-minute dynamic [¹¹C]PiB-PET scan and brain biopsy tissue. Parametric non-displaceable binding potential (BPND) images showed low specific binding in the amyloidoma (BPND = 0.23), while relative tracer delivery was adeq...

This preclinical study explored the feasibility of assessing P-glycoprotein (P-gp) function in both brain and gastrointestinal (GI) tract of rats using positron emission tomography (PET) following oral administration of [18F]MC225. Different oral administration protocols were evaluated, and radioactivity uptake was compared with uptake following in...

Purpose [ ¹⁸ F]NaF PET has become an increasingly important tool in clinical practice toward understanding and evaluating diseases and conditions in which bone metabolism is disrupted. Full kinetic analysis using nonlinear regression (NLR) with a two-tissue compartment model to determine the net rate of influx ( K i ) of [ ¹⁸ F]NaF is considered th...

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic bone disorder characterized by episodic flare-ups in connective tissue, which are frequently followed by the formation of heterotopic ossification. The absence of available plasma-soluble biomarkers for flare-ups or heterotopic bone formation poses severe challenges to the monitoring of...

Methods to shorten [18F]FDG Patlak PET imaging procedures ranging from 65-90 to 20-30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [18F]FDG Patlak i...

The use of Ultra-Low-Dose computedtomography (ULD-CT) in PET/CT imaging is gainingattention due to its potential to significantly reduceradiation exposure, which is crucial for patient safety.Accurate organ segmentation is essential for treatmentplanning, particularly in radiotherapy where it aids indelineating target volumes and organs at risk. Th...

Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare, genetic disease in which heterotopic bone is formed in muscles, tendons and ligaments throughout the body. Disease progression is variable over time and between individuals. ¹⁸ F-fluoride uptake in newly formed bone can be evaluated using [ ¹⁸ F]NaF (i.e., sodiumfluoride) PET/CT, ide...

Because of the limited axial field of view of conventional PET scanners, the internal carotid arteries are commonly used to obtain an image-derived input function (IDIF) in quantitative brain PET. However, time-activity curves extracted from the internal carotids are prone to partial-volume effects due to the limited PET resolution. This study aime...

Reducing proteinuria is a crucial approach in preventing kidney function loss. Previous preclinical studies indicated that caloric restriction (CR) imposed at a young age protects against age‐related proteinuria. However, these studies have not explored CR in established renal disease. Therefore, this study aimed to investigate the impact of CR on...

Immuno-positron emission tomography (immunoPET) enables imaging of specific targets that play a role in targeted therapy and immunotherapy, such as antigens on cell membranes, targets in the disease microenvironment or immune cells. The most common immunoPET applications use a monoclonal antibody labeled with a relatively long-lived positron emitte...

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essentia...

Background Amyloid‐β (Aβ) PET is commonly used for studying the earliest phases of Alzheimer’s disease (AD) in cognitively unimpaired (CU) individuals. In this group, the expected changes in Aβ pathology are small, which emphasizes the importance of selecting a method with the highest possible precision for measuring these changes. This study compa...

Background Amyloid‐ß (Aß) PET is commonly used for studying the earliest phases of Alzheimer’s disease (AD) in cognitively unimpaired (CU) individuals. In this group, the expected changes in Aß pathology are small, which emphasizes the importance of selecting a method with the highest possible precision for measuring these changes. This study compa...

Background The use of computed tomography (CT) for attenuation correction (AC) in whole‐body PET/CT can result in a significant contribution to radiation exposure. This can become a limiting factor for reducing considerably the overall radiation exposure of the patient when using the new long axial field of view (LAFOV) PET scanners. However, recen...

Background The need for arterial blood data in quantitative PET research limits the wider usability of this imaging method in clinical research settings. Image-derived input function (IDIF) approaches have been proposed as a cost-effective and non-invasive alternative to gold-standard arterial sampling. However, this approach comes with its own lim...

Background Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging techniques and clinical trials. However, new invasive pressure indices that do not require hyperemia have rece...

Simple Summary Recently: long axial field-of-view (LAFOV) positron emission tomography (PET) scanners have been introduced. Compared with conventional short axial field-of-view systems, these new scanners have a larger axial coverage and, thereby, a higher system sensitivity. This provides new opportunities for applying PET in clinical practice. So...

Introduction P-glycoprotein (P-gp) is one of the most studied efflux transporters at the blood-brain barrier. It plays an important role in brain homeostasis by protecting the brain from a variety of endogenous and exogeneous substances. Changes in P-gp function are associated both with the onset of neuropsychiatric diseases, including Alzheimer’s...

The purpose of this study was to quantify any differences between the SUVs of 89Zr immuno-PET scans obtained using a PET/CT system with a long axial field of view (LAFOV; Biograph Vision Quadra) compared to a PET/CT system with a short axial field of view (SAFOV; Biograph Vision) and to evaluate how LAFOV PET scan duration affects image noise and S...

Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical p...

The traditional design of PET target engagement studies is based on a baseline scan and one or more scans after drug administration. We here evaluate an alternative design in which the drug is administered during an on-going scan (i.e., a displacement study). This approach results both in lower radiation exposure and lower costs. Existing kinetic m...

The oral route is the most widely used and preferable way of drug administration. Several pharmacokinetic processes play a role in the distribution of administered drugs. Therefore, accurate quantification of absorption, distribution, metabolism, excretion, and characterisation of drug kinetics after oral administration is extremely important for d...

Transforming growth factor β (TGFβ) activity is perturbed in remodelled pulmonary vasculature of patients with pulmonary arterial hypertension (PAH), cancer, vascular diseases and developmental disorders. Inhibition of TGFβ, which signals via activin receptor-like kinase 5 (ALK5), prevents progression and development of experimental PAH. The purpos...

Purpose: To give a comprehensive literature overview of alterations in regional cerebral glucose metabolism, measured using [18F]FDG PET, in conditions associated with hyperkinetic movement disorders and ataxia. In addition, correlations between glucose metabolism and clinical variables as well as the effect of treatment on glucose metabolism are...

Pharmacokinetic modelling with arterial sampling is the gold standard for analysing dynamic PET data of the brain. However, the invasive character of arterial sampling prevents its widespread clinical application. Several methods have been developed to avoid arterial sampling, in particular reference region methods. Unfortunately, for some tracers...

Importance Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know the...

Current PET datasets are becoming larger, thereby increasing the demand for fast and reproducible processing pipelines. This paper presents a freely available, open source, Python-based software package called NiftyPAD, for versatile analyses of static, full or dual-time window dynamic brain PET data. The key novelties of NiftyPAD are the analyses...

Alzheimer’s disease is characterized by regional reductions in cerebral blood flow (CBF) and the gold standard for measuring CBF is [15O]H2O PET. Recently, proxies of relative CBF, derived from the early distribution phase of amyloid‐β and tau tracers, have gained attention. It has been hypothesized that relative CBF is likely to have higher precis...

This review describes the main benefits of using long axial field of view (LAFOV) PET in clinical applications. As LAFOV PET is the latest development in PET instrumentation, many studies are ongoing that explore the potentials of these systems, which are characterized by ultra-high sensitivity. This review not only provides an overview of the publ...

Purpose To relate [ ¹⁸ F]fluoride uptake on PET with abnormalities on magnetic resonance imaging (MRI) and conventional radiography (CR) in ankylosing spondylitis (AS) patients. Methods Ten clinically active AS patients (female 6/10, age 38 ± 11 years) were included, and both spine and SI-joints were examined. PET scans were dichotomously scored f...

Alzheimer’s disease is characterized by regional reductions in cerebral blood flow (CBF) and the gold standard for measuring CBF is [15O]H2O PET. Recently, proxies of relative CBF, derived from the early distribution phase of amyloid‐β and tau tracers, have gained attention. It has been hypothesized that relative CBF is likely to have higher precis...

The traditional design of PET target engagement studies is based on a baseline scan and one or more scans after drug administration. We here evaluate an alternative design in which the drug is administered during an on-going scan (i.e., a displacement study). This approach results both in lower radiation exposure and lower costs. Existing kinetic m...

Multiple sclerosis (MS) is an inflammatory demyelinating disease. Current treatments are focussed on immune suppression to modulate pathogenic activity that causes myelin damage. New treatment strategies are needed to prevent demyelination and promote remyelination. Development of such myelin repair therapies require a sensitive and specific biomar...

Background Excellent performance characteristics of the Vision Quadra PET/CT, e.g. a substantial increase in sensitivity, allow for precise measurements of image-derived input functions (IDIF) and tissue time activity curves. Previously we have proposed a method for a reduced 30 min (as opposed to 60 min) whole body ¹⁸F-FDG Patlak PET imaging proce...

Alzheimer’s disease is characterized by regional reductions in cerebral blood flow (CBF). Although the gold standard for measuring CBF is [ ¹⁵ O]H 2 O PET, proxies of relative CBF, derived from the early distribution phase of amyloid and tau tracers, have gained attention. The present study assessed precision of [ ¹⁵ O]H 2 O derived relative and ab...

A standardized approach to acquiring amyloid PET images increases their value as disease and drug response biomarkers. The majority of 18F PET amyloid brain scans often are assessed only visually (per regulatory labels), with a binary decision indicating the presence or absence of Alzheimer's disease amyloid pathology. Minimizing technical variance...

Purpose Multiple sclerosis (MS) is a disease characterized by inflammatory demyelinated lesions. New treatment strategies are being developed to stimulate myelin repair. Quantitative myelin imaging could facilitate these developments. This first-in-man study aimed to evaluate [ ¹¹ C]MeDAS as a PET tracer for myelin imaging in humans. Methods Six h...

Purpose Current European Association of Nuclear Medicine (EANM) Research Ltd. (EARL) guidelines for the standardisation of PET imaging developed for conventional systems have not yet been adjusted for long axial field-of-view (LAFOV) systems. In order to use the LAFOV Siemens Biograph Vision Quadra PET/CT (Siemens Healthineers, Knoxville, TN, USA)...

Background Despite its widespread use, the semi-quantitative standardized uptake value ratio (SUVR) may be biased compared with the distribution volume ratio (DVR). This bias may be partially explained by changes in cerebral blood flow (CBF) and is likely to be also dependent on the extent of the underlying amyloid-β (Aβ) burden. This study aimed t...

The transforming growth factor β (TGFβ) pathway plays a complex role in cancer biology, being involved in both tumour suppression as well as promotion. Overactive TGFβ signalling has been linked to multiple diseases, including cancer, pulmonary arterial hypertension, and fibrosis. One of the key meditators within this pathway is the TGFβ type I rec...

Objective To investigate the potential of whole body positron emission tomography/computed tomography (PET/CT) with a macrophage tracer to image arthritis in patients with early rheumatoid arthritis (RA). Methods Thirty-five previously untreated, clinically active early RA patients underwent whole body PET/CT scanning with the macrophage tracer (...

Objective To determine whether macrophage positron emission tomography (PET)/computed tomography (CT) imaging using ( R )-[ ¹¹ C]PK11195 at 0 and 2 weeks is associated with clinical response at 13 weeks in patients with early rheumatoid arthritis (RA). Methods Whole-body ( R )-[ ¹¹ C]PK11195 PET/CT scans were performed at baseline and after 2 week...

The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [ ¹⁸ F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of...

In this contribution, several opportunities and challenges for long axial field of view (LAFOV) PET are described. It is an anthology in which the main issues have been highlighted. A consolidated overview of the camera system implementation, business and financial plan, opportunities and challenges is provided. What the nuclear medicine and molecu...

Background Accurate quantitative measures of amyloid beta (Aβ) plaques are needed to identify individuals with subthreshold Aβ levels or for measuring small changes over time. To this end, dynamic or dual‐time‐window scanning protocols are required. Optimal pharmacokinetic models for quantifying Aβ burden using both [ ¹⁸ F]flutemetamol and [ ¹⁸ F]f...

Background In Alzheimer’s disease (AD), reductions in cerebral blood flow (CBF) have been reported and these may be used as proxy for measuring treatment efficacy or disease progression. The gold standard technique for measuring CBF is [ ¹⁵ O]H 2 O positron emission tomography (PET). Recent studies, however, have reported high correlations between...

Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that are widely used to prevent cardiovascular diseases. However, a series of pleiotropic mechanisms have been associated with statins, particularly with atorvastatin. Therefore, the assessment of [¹⁸F]atorvastatin kinetics with positron emission tomography (PET) may elucidate t...

Purpose In order to achieve comparability of image quality, harmonisation of PET system performance is imperative. In this study, prototype harmonisation criteria for PET brain studies were developed. Methods Twelve clinical PET/CT systems (4 GE, 4 Philips, 4 Siemens, including SiPM-based “digital” systems) were used to acquire 30-min PET scans of...

Background Treat-to-target strategies for rheumatoid arthritis (RA) have shown significant improvements in therapy outcomes. Nevertheless, it usually takes a minimum of 12 weeks before clinical assessment of treatment response can be made. Quantitative positron emission tomography (PET) has shown potential to predict clinical response at a very ear...

Background: Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence. Methods: We used neuronavigation to acquire 133 image-guided an...

Aims To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (ΔT1) with [15O]H2O positron emission tomography (PET) measurements of quantitative myocardial perfusion. Methods and results Forty-three patients with suspected obstructed coronary artery disease underwent [15O]H2O PET and CMR at 1.5-T, including rest and adenosine stre...

The objective of the study was the construction of a generic curriculum development model for the use of biomedical physics (BMP) educators teaching the non-physics healthcare professions (HCP) in Europe. A comprehensive, qualitative cross-sectional Europe-wide survey of the curricula delivered by BMP in Faculties of Medicine and Health Sciences (F...

From its inception, EFOMP has pursued a policy to improve and coordinate education and training of medical physicists across all its participating European countries. Several EFOMP policy statements on education and training have been published and surveys have been held to get an overview of the actual situation. At the beginning of 2020 a new sur...

Purpose: Moderate-to-high correlations have been reported between the [11C]PiB PET-derived relative tracer delivery rate R1 and relative CBF as measured using [15O]H2O PET, supporting its use as a proxy of relative CBF. As longitudinal PET studies become more common for measuring treatment efficacy or disease progression, it is important to know t...

Background Detecting subtle-to-moderate biomarker changes such as those in amyloid PET imaging becomes increasingly relevant in the context of primary and secondary prevention of Alzheimer’s disease (AD). This work aimed to determine if and when distribution volume ratio (DVR; derived from dynamic imaging) and regional quantitative values could imp...

Background: Over the last decades, many brain imaging studies have contributed to new insights in the pathogenesis of psychiatric disease. However, in spite of these developments, progress in the development of novel therapeutic drugs for prevalent psychiatric health conditions has been limited. Objective: In this review, we discuss translationa...

To date, three fluorine-18 labelled tracers have been approved for assessing cerebral amyloid plaques pathology to assist in the diagnosis of Alzheimer's Disease (AD). Although scanning protocols are relatively similar across tracers, FDA/EMA approved visual rating guidelines to render scans as positive or negative differ between the three tracers....

Optimal pharmacokinetic models for quantifying amyloid beta (Aβ) burden using both [¹⁸F]flutemetamol and [¹⁸F]florbetaben scans have previously been identified at a region of interest (ROI) level. The purpose of this study was to determine optimal quantitative methods for parametric analyses of [¹⁸F]flutemetamol and [¹⁸F]florbetaben scans. Forty-si...

Objectives Non-small cell lung cancer (NSCLC) tumors harboring common (exon19del, L858R) and uncommon (e.g. G719X, L861Q) activating epidermal growth factor receptor (EGFR) mutations are best treated with EGFR tyrosine kinase inhibitors (TKI) such as the first-generation EGFR TKI erlotinib, second-generation afatinib or third-generation osimertinib...

Objective To study the genetic contribution to the start of Alzheimer's disease with amyloid and tau biomarkers in cognitively intact older identical twins. Methods We studied in 96 monozygotic twin‐pairs relationships between Aβ aggregation as measured by the ratio Aβ1‐42/1‐40 in cerebrospinal fluid (CSF, n=126) and positron emission tomography (...

Fibrodysplasia ossificans progressiva (FOP) is a genetic disease characterized by the formation of heterotopic ossification (HO) in connective tissues. HO first develops in the thoracic region, before more peripheral sites are affected. Due to HO along the thoracic cage, its movements are restricted and pulmonary function deteriorates. Because deve...

Background Detecting amyloid‐β plaque accumulation in individuals who are initially amyloid negative can help understand the earliest stages of Alzheimer’s disease (AD). This study aimed to determine sample sizes that would be needed to detect statistically significant longitudinal changes using semi‐ (standard uptake value ratios; SUVR) and quanti...

Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However,...

Purpose: Sorafenib leads to clinical benefit in a subgroup of patients, while all are exposed to potential toxicity. Currently, no predictive biomarkers are available. The purpose of this study was to evaluate whether 11C-sorafenib and 15O-H2O PET have potential to predict treatment efficacy. Methods: In this prospective exploratory study, 8 patien...

Background The standard reference region (RR) for amyloid-beta (Aβ) PET studies is the cerebellar grey matter (GMCB), while alternative RRs have mostly been utilized without prior validation against the gold standard. This study compared five commonly used RRs to gold standard plasma input-based quantification using the GMCB. Methods Thirteen subj...

Aims : This study sought to determine the prognostic value of combined functional testing using positron emission tomography (PET) perfusion imaging and anatomical testing using coronary computed tomography angiography (CCTA)-derived stenosis severity and plaque morphology in patients with suspected coronary artery disease (CAD). Methods and resu...

This chapter provides an overview of the basic principles of quantification of cerebral PET studies using compartmental modelling. Both single- and two-tissue compartment models are presented with emphasis on volume of distribution and non-displaceable binding potential as outcome measures. Next, both full and simplified reference tissue models are...

Purpose Several studies found reduced retinal thickness on optical coherence tomography (OCT) in Alzheimer’s disease (AD), even in preclinical stages, labelling this technique of interest as biomarker. In this study, we examine retinal thickness changes in preclinical AD, as defined by cognitively normal individuals with amyloid‐beta (Aβ) on positr...

Introduction: Only a subgroup of non-small cell lung cancer (NSCLC) patients benefit from treatment using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) such as afatinib. Tumour uptake of [18F]afatinib using positron emission tomography (PET) may identify those patients that respond to afatinib therapy. Therefore, the aim...

In the field of rare bone diseases in particular, a broad care team of specialists embedded in multidisciplinary clinical and research environment is essential to generate new therapeutic solutions and approaches to care. Collaboration among clinical and research departments within a University Medical Center is often difficult to establish, and ma...

Purpose To compare cardiac magnetic resonance imaging (CMR) with [¹⁵O]H2O positron emission tomography (PET) for quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with coronary artery disease (CAD). Methods Fifty-nine patients with stable CAD underwent CMR and [¹⁵O]H2O PET. The CMR imaging protoco...

PurposeThis joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results...

Objective To develop and evaluate a model for staging cortical amyloid deposition using PET with high generalizability. Methods 3027 subjects (1763 Cognitively Unimpaired (CU), 658 Impaired, 467 Alzheimer’s disease (AD) dementia, 111 non-AD dementia, and 28 with missing diagnosis) from six cohorts (EMIF-AD, ALFA, ABIDE, ADC, OASIS-3, ADNI) who und...

Objective: To study the genetic contribution to the start of Alzheimer's disease as signified by abnormalities in amyloid and tau biomarkers in cognitively intact older identical twins. Methods: We studied in 96 monozygotic twin-pairs relationships between Aβ aggregation as measured by the ratio Aβ1-42/1-40 in cerebrospinal fluid (CSF) and positron...

Background Clinical assessment of arthritis is the cornerstone in the diagnosis and treatment of rheumatoid arthritis (RA). Nevertheless, reliable determination of (sub)clinical arthritis can be difficult, especially in the feet. Advanced imaging techniques may contribute to early diagnosis and therapy monitoring through sensitive detection and (qu...