Emerging Functional Imaging Biomarkers of Tumour Responses to Radiotherapy

Abstract

Tumour responses to radiotherapy are currently primarily assessed by changes in size. Imaging permits non-invasive, whole-body assessment of tumour burden and guides treatment options for most tumours. However, in most tumours, changes in size are slow to manifest and can sometimes be difficult to interpret or misleading, potentially leading to prolonged durations of ineffective treatment and delays in changing therapy. Functional imaging techniques that monitor biological processes have the potential to detect tumour responses to treatment earlier and refine treatment options based on tumour biology rather than solely on size and staging. By considering the biological effects of radiotherapy, this review focusses on emerging functional imaging techniques with the potential to augment morphological imaging and serve as biomarkers of early response to radiotherapy.

Keywords: diffusion-weighted imaging; functional imaging; hyperpolarised 13C; magnetic resonance imaging; positron emission tomography; radiotherapy; treatment response.

Figure 1

Single photon emission computed tomography (SPECT) imaging of cell death in vivo in Eμ-Myc tumours. Imaging of (^99mTc)-labelled C2Am at 2 h after probe administration and 24 h after drug treatment. SPECT/CT of representative Eμ-Myc mice before (BT, left) and after (AT, right) cyclophosphamide treatment. Top—maximum intensity projections (MIPs); middle—axial section through the cervical tumour; bottom—axial section through the axillary and mediastinal tumours. Tumours are indicated with arrowheads. Reproduced with permission from Neves et al. © SNMMI [20].

Figure 2

Perfusion magnetic resonance imaging (MRI) with pulsed arterial spin labelling (pASL) of a patient with a frontal high-grade oligodendroglioma with a focus of hyperperfusion (white arrow) identifying recurrent disease post-surgery and chemotherapy. Axial sections have the following sequences: (a) T₁-weighted contrast-enhanced and (b) pASL. Images courtesy of Dr Harpreet Hyare, University College London Hospital.

Figure 3

Diffusion-weighted MRI of a patient with glioblastoma multiforme. The necrotic core shows facilitated diffusion with a surrounding ring of restricted diffusion indicative of progressive disease. Axial sections have the following sequences: (a) T₁-weighted contrast-enhanced; (b) T₂ FLAIR (fluid-attenuated inversion recovery); (c) diffusion-weighted imaging (DWI); (d) apparent diffusion coefficient (ADC) map. Images courtesy of Dr Harpreet Hyare, University College London Hospital.

Figure 4

Detection of recurrence in two patients using ¹⁸F-choline and amide proton transfer- chemical exchange saturation transfer (APT-CEST). Patient 1 (a–d): WHO grade I pilocytic astrocytoma initially treated with radiotherapy. Imaging performed four years later when the patient re-presented with seizures. Patient 2 (e–h): WHO grade IV glioblastoma multiforme treated with surgery and chemoradiotherapy. Imaging surveillance performed eighteen months after completing initial treatment. Tumours indicated with white arrowheads. Abbreviations: T₂W FLAIR, T₂-weighted fluid-attenuated inversion recovery; T₁W CE, T₁-weighted contrast enhanced. Images courtesy of Dr Harpreet Hyare, University College London Hospital.

Figure 5

A T4N0M0 rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy. (b and c) Prior to treatment, the lesion is ¹⁸F-FDG-avid; (g and h) after chemoradiation, there is minimal residual uptake despite a minimal change in tumour volume. At subsequent resection, no residual disease remained and the patient was down-staged to ypT0N0M0. (a and f) axial CT; (b and g) axial ¹⁸F-FDG-PET; (c and h) PET/CT fusion; (d and i) axial T₂W MRI; (e and j) coronal T₂W MRI. The tumour is indicated by arrowheads and dashed outline. All ¹⁸F-FDG-PET images are scaled between an standardised uptake value (SUV) of 0–5.

Figure 6

Representative images following injection of hyperpolarised (1-¹³C)pyruvate in a C6 glioma-bearing rat before (top, PreTx) and 96 h after radiotherapy (bottom, PostTx). Images of (1-¹³C)pyruvate ((1-¹³C)pyr) and (1-¹³C)lactate ((1-¹³C)lac) overlaid on coronal T₁W MR images. A reduction in (1-¹³C)lactate production was observed in all tumours after 15 Gy irradiation without decreases in tumour volume. Adapted with permission from Day et al. [142].

Figure 7

¹⁸F-dihydroxyphenylalanine (¹⁸F-DOPA) uptake in a patient with glioblastoma multiforme treated with chemoradiotherapy before (top row) and after 12 weeks (bottom row). From left to right: Post-gadolinium T₁W axial MRI; T₂W axial MRI; fusion PET/MRI with ¹⁸F-DOPA.