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Spotlight on: “dynamic PET/CT imaging”

Background

Positron emission tomography/computed tomography (PET/CT or PET) has an established role in clinical practice, particularly for oncology. Interpretation of results typically involves a composite approach of qualitative evaluation by the reporting specialist as well as support from semi-quantitative measurements, commonly the maximum standardised uptake value (SUVMax). Acquisition protocols reflect this approach and are commonly based on static imaging at a pre-established time point following injection.

Dynamic PET, on the other hand, involves the continuous imaging over a pre-defined period immediately after injection, acquiring kinetic information. Tracer kinetic modelling based on several different models or principles can allow for parametric images as well as the extraction of time–activity curves (TACs) within selected volumes of interest [1].

While dynamic protocols are widely used in SPECT imaging, similar approaches in PET imaging outside of cerebral PET or research setting are still debated and currently not well established.

Clinical utility of dynamic PET (dPET) in oncology: is more… more?

Given the well-established role of PET/CT in the field of oncology, it is no surprise that dynamic PET protocols have been trialled in a conspicuous number of primary cancers. Some findings are of some interest, although with two main limitations:

  1. 1.

    Most of the studies only include a limited number of patients in a retrospective setting, which certainly impacts their significance.

  2. 2.

    Some research-based protocols, for example, 15O-oxygen for quantification of brain oxygen extraction and metabolism, require complex procedures such as arterial blood sampling that are not easy to perform in daily clinical setting.

In a 2020 study from colleagues in Budapest, Hungary, 34 patients with breast cancer were assessed by means of dynamic PET to investigate correlations between tumour phenotype and FDG kinetics, with a particular focus on tumour microenvironments. Dynamic acquisitions commenced immediately after injection of F-18 FDG and lasted 60 min. The authors found dynamic imaging to be less susceptible to tumour microenvironment-led variations, which could potentially assist in identifying more aggressive breast cancer subtypes [2].

The role of dynamic PET protocols in characterising pulmonary nodules was trialled in a small cohort of twenty patients with 21 pulmonary nodules detected on CT in a 2021 English study [3]. Each patient underwent a 60 min dynamic respiratory gated PET/CT scan, followed by a standard static acquisition 60 min post-injection. Dynamic PET data was analysed with a Patlak plot model based on a two-tissue compartmental model with irreversibly trapped tracer. The authors, however, failed to demonstrate the benefit of dynamic protocols over conventional static protocols and perfusion CT in this cohort.

Few studies have investigated the role of dynamic imaging in non-FDG PET radiotracers as well.

The diagnostic and prognostic potential of dynamic protocols of 18F-FET (FET), a well-known tyrosine analogue-based tracer highly specific for glioma, has been explored in the past [4]. More recently, interesting data on 45 patients with known disease were published by an Italian group [5]. The colleagues analysed the added value of performing a FET PET scan following an MRI and utilised a dynamic protocol of 35 frames within the first 5 min post-injection, concluding that FET PET had good diagnostic performance in differentiating between glioma recurrence and post-treatment changes in this setting.

Dynamic protocols for acquisition of 18F-choline in clinical settings have been proposed by an Italian group to overcome the urinary excretion of the tracer, which can impend the capacity to interpret findings within the pelvis [6]. The authors suggest that an early acquisition (static or dynamic) of the pelvis prior to the excretion of the tracer within the ureters may improve the readability of the study when paired with a standard static whole body acquisition.

More recently, a direct comparison of dynamic imaging with 18F-choline and 18-F-DCFPYL (2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) was performed within a small sample size of patients with prostate cancer [7]. The authors compared the two with regard to the capacity to identify the dominant intraprostatic lesion using a 22-min dynamic imaging protocol with multiple frames of acquisition times from 10 to 180 s and kinetic parameters, suggesting possible superiority of 18F-DCFPYL over 18F-choline in this setting.

A German group published their data on a small cohort of 25 patients with biochemical progression of prostate cancer who underwent dynamic 18F-PSMA-1007 PET scans of the pelvic area and the lower abdomen for 60 min after injection [8]. In the study, dynamic PET did not demonstrate any clinical advantage in terms of lesions identified over static protocols. However, potentially useful information was extracted from the data relating to pharmacokinetics and high tracer binding/internalisation in tumour tissue. These aspects may translate to clinical practice in the future by informing patient selection for PSMA-targeted therapies such as PSMA-617 labelled with 177Lu or 225Ac.

In summary, while dynamic PET protocols have the potential to extrapolate potentially clinically relevant information, currently this does not seem to translate into clinical relevance. This is partially due to the overall still poor comprehension of molecular tumour biology, and partly due to the complicated procedure of obtaining such data. However, there are clinical scenarios such as assessing responses to systemic therapy where dynamic PET imaging may assist clinicians to differentiate between residual tumour and inflammatory tissue.

The PET total body revolution: one-stop shop for cancer patients?

The restricted field of view of bed positions in the majority of commercially available PET cameras is a major limitation to the feasibility of implementing dynamic protocols in day-to-day practice, as it is in SPECT cameras where it could be beneficial, in example, for tree-phase bone scans.

Poor axial coverage also limits the quality of the scan and reduces the capacity to count coincidence photons.

Total-body-length PET scanners (TBPET) represent an important technological advancement to reduce these issues. While slightly different in specifications, they all allow to perform scans with a significantly larger field of view, thus reducing the potential dosage or acquisition time, while improving the practicality of dynamic imaging [9, 10]. Another advantage may be the increased signal-to-noise ratio, which might lead to easier detection of smaller lesions.

Dynamic protocols established on TBPET may provide more accurate and detailed data, improving both the quality of the quantification processes as well as excellent temporal sampling due to the larger field of view.

A possible point of discussion is the implementation of dynamic protocols that still include static imaging at 1 h post-injection, which are currently required for appropriate readings which use defined criteria (for example, response assessment by means of DEAUVILLE criteria for lymphoma patients) [11].

It has also been suggested that in the future, the role of TBPET could be strategic in the immune-PET era, when patients are likely to require more frequent assessments by means of PET scans and therefore cumulative radiation dose will pose a greater risk. TBPET may reduce cumulative dose to lower levels with potential benefits to the patient [12].

Conclusion

There seems to be a newborn (or perhaps re-born) interest in dynamic PET within the molecular imaging community.

This is due to the more elegant approach of modern oncology to treatment, notably with the advent of the immunotherapy era and also important technological advancements such as total body PET.

Both of these factors are pushing researchers to investigate new and innovative approaches to dynamic PET/CT imaging in oncology.

On one hand, the understanding of tumour microenvironment is growing and the insight that comes from kinetic data such as that provided by dynamic PET protocols can fuel a partnership with potentially important clinical impact for clinicians. This will likely further be developed as new radiopharmaceuticals become clinically available.

On the other hand, the advent of TBPET will certainly make it easier for clinicians to investigate and potentially define the role of dynamic PET in clinical practice. While some encouraging results have been documented in smaller cohorts, stronger evidence in large populations is lacking and would be greatly welcomed.

The potential benefit to patients and the molecular imaging community, while not yet fully scoped, will hopefully be better defined in the near future and head at full speed into the exciting theranostics era.

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Morigi, J.J., Kovaleva, N. & Phan, S. Spotlight on: “dynamic PET/CT imaging”. Clin Transl Imaging 10, 239–241 (2022). https://doi.org/10.1007/s40336-022-00500-0

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Keywords

  • Dynamic PET
  • Molecular imaging
  • Total body PET
  • Tumour microenvironment