PET tracers in glioblastoma: Toward neurotheranostics as an individualized medicine approach

Abstract

Over the past decade, theragnostic radiopharmaceuticals have been used in nuclear medicine for both diagnosis and treatment of various tumors. In this review, we carried out a literature search to investigate and explain the role of radiotracers in the theragnostic approach to glioblastoma multiform (GBM). We primarily focused on basic and rather common positron emotion tomography (PET) radiotracers in these tumors. Subsequently, we introduced and evaluated the preclinical and clinical results of theranostic-based biomarkers including integrin receptor family, prostate-specific membrane antigen (PSMA), fibroblast activated protein (FAP), somatostatin receptors (SRS), and chemokine receptor-4 (CXCR4) for patients with GBM to confer the benefit of personalized therapy. Moreover, promising research opportunities that could have a profound impact on the treatment of GBM over the next decade are also highlighted. Preliminary results showed the potential feasibility of the theragnostic approach using theses biomarkers in GBM patients.

Keywords: chemokine receptor-4 (CXCR4); fibroblast activated protein (FAP); glioblastoma multiform (GBM); neuro-Oncology; prostate-specific membrane antigen (PSMA); somatostatin receptors (SRS); theranostics.

Figure 1

A 58-year-old man with high-grade glioma underwent brain ¹⁸F-FET PET/CT indicated intense radiotracer uptake (SUVmax = 7.68) in the left parietal lobe. (A) Accordingly, the tumor showed no change in Gd enhancement on FLAIR axial MRI with Gd. (B) Therefore, recurrence or residual disease was noted in the left parietal lobe.

Figure 2

A 62-year-old man with high-grade glioma (WHO IV) that underwent ⁶⁸Ga-pentixafor PET/CT. A large hypo-dense cerebral lesion (7*5.5 cm) was observed in the right parieto-occipital lobe with ⁶⁸Ga-Pentixafor (Pars-Cixafor^TM) uptake (SUVmax: 1.87), central photopenia (probably necrosis) and good tumor delineation.

Figure 3

A 55-year-old patient with a history of GBM in the right frontotemporal lobe that underwent surgery and external beam radiation therapy and received ¹⁷⁷Lu-DOTATATE. On ⁶⁸Ga-Pentixather and ⁶⁸Ga-FAPI imaging, there were three cerebral mass lesions in the right frontal and temporoparietal lobs, including a 11 × 15 mm lesion in the temporal lobe with SUV max = 4.15 (⁶⁸Ga-Pentixather) and SUVmax = 4.154 (⁶⁸Ga-FAPI), a 27 × 15 mm lesion in the temporal lobe (peri ventricular) with SUVmax = 1.97 (⁶⁸Ga-Pentixather) and SUVmax = 2.68 (⁶⁸Ga-FAPI), and a third lesion with a diameter of 12 × 14 mm in the right temporal lobe with SUVmax = 2.23 (⁶⁸Ga-Pentixather) and 1.82 (⁶⁸Ga-FAPI).

Figure 4

A 55-year-old man with recurrent high-grade glioma in the right temporoparietal region underwent ⁶⁸Ga-FAPI PET/CT showing three cerebral lesions in the right frontal and right temporoparietal regions (left side). The patient received one cycle of ¹⁷⁷Lu-FAPI (right side).