The Use of a Non-Conventional Long-Lived Gallium Radioisotope Ga-66 Improves Imaging Contrast of EGFR Expression in Malignant Tumours Using DFO-ZEGFR:2377 Affibody Molecule

• Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies. EGFR-targeted therapy extends survival of patients with disseminated cancers. Radionuclide molecular imaging of EGFR expression would make EGFR-directed treatment more personalized and therefore more efficient. A previous study demonstrated that affibody molecule [Ga-68]Ga-DFO-ZEGFR:2377 permits specific positron-emission tomography (PET) imaging of EGFR expression in xenografts at 3 h after injection. We anticipated that imaging at 24 h after injection would provide higher contrast, but this is prevented by the short half-life of Ga-68 (67.6 min). Here, we therefore tested the hypothesis that the use of the non-conventional long-lived positron emitter Ga-66 (T-1/2 = 9.49 h, beta(+) = 56.5%) would permit imaging with higher contrast. Ga-66 was produced by the Zn-66(p,n)Ga-66 nuclear reaction and DFO-ZEGFR:2377 was efficiently labelled with Ga-66 with preserved binding specificity in vitro and in vivo. At 24 h after injection, [Ga-66]Ga-DFO-ZEGFR:2377 provided 3.9-fold higher tumor-to-blood ratio and 2.3-fold higher tumor-to-liver ratio than [Ga-68]Ga-DFO-ZEGFR:2377 at 3 h after injection. At the same time point, [Ga-66]Ga-DFO-ZEGFR:2377 provided 1.8-fold higher tumor-to-blood ratio, 3-fold higher tumor-to-liver ratio, 1.9-fold higher tumor-to-muscle ratio and 2.3-fold higher tumor-to-bone ratio than [Zr-89]Zr-DFO-ZEGFR:2377. Biodistribution data were confirmed by whole body PET combined with magnetic resonance imaging (PET/MRI). The use of the positron emitter Ga-66 for labelling of DFO-ZEGFR:2377 permits PET imaging of EGFR expression at 24 h after injection and improves imaging contrast.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

epidermal growth factor receptor

affibody molecule

PET imaging

gallium-66

ZEGFR

2377

A431 xenograft

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)