Non-conventional and Investigational PET Radiotracers for Breast Cancer: A Systematic Review

Abstract

Breast cancer is one of the most common malignancies in women, with high morbidity and mortality rates. In breast cancer, the use of novel radiopharmaceuticals in nuclear medicine can improve the accuracy of diagnosis and staging, refine surveillance strategies and accuracy in choosing personalized treatment approaches, including radioligand therapy. Nuclear medicine thus shows great promise for improving the quality of life of breast cancer patients by allowing non-invasive assessment of the diverse and complex biological processes underlying the development of breast cancer and its evolution under therapy. This review aims to describe molecular probes currently in clinical use as well as those under investigation holding great promise for personalized medicine and precision oncology in breast cancer.

Keywords: FAPI; FES; FLT; PET; PSMA; breast cancer; molecular imaging; radiotracers.

Figure 1

The figure provides a schematic representation of surrogate intrinsic BC subtypes (14), based on histologic and molecular features, which have significant implication for prognosis and treatment choice.

Figure 2

The figure shows a schematic representation of all major radiotracers currently in clinical use in BC or under evaluation.

Figure 3

[¹⁸F]F-FDG PET/CT in BC staging. On the left, the case of an 83-year-old lady with previous in situ BC on the right and suspected recurrence of breast cancer on the left. Staging [¹⁸F]F-FDG PET/CT scan showed focal and elevated uptake at the level of the breast lesion on the left upper-external quadrant (C) and at the level of several ipsilateral axillary lymph nodes suspected for secondary localization of disease (A,B), as also shown in the MIP images (D). The cytologic finding was consistent with the clinical suspicion of IBC-NST recurrence (ER 98%, PR 99%, anti-Ki67 23%, anti c-erbB2 negative). On the right, the case of a 72-year-old lady hospitalized for dyspnea and CT findings of right pleural effusion concomitant to left mammary nodule and mediastinal lymphadenopathies. Staging PET scans did not show any FDG uptake in the suspicious lesions reported on CT scan, either in the breast (C) or in the ipsilateral axillary lymph nodes (A,B), as also shown in MIP images (D). The cytological findings were consistent with the clinical suspicion of ILBC (ER 78%, PR 55%, anti-Ki67 46%, anti c-erbB2 negative).

Figure 4

[¹⁸F]F-DOPA PET and MRI results in a case of differential diagnosis between tumefactive plaque due to multiple sclerosis and brain metastasis from breast cancer. Seventy-one years old female patient previously treated for BC. ceMRI showed the presence of at least two hyperintense at T2 sequences (A) and hypointense at T1 sequences (A) (the largest in left frontal lobe). [¹⁸F]F-DOPA PET/CT showed a very mild tracer uptake supporting the hypothesis of tumefactive lesion due to multiple sclerosis (B). ceMRI performed 3 months after therapy administration showed reduction in both lesion size and contrast enhancement (C).

Figure 5

Low intensity MIP images showing the normal biodistribution of [¹⁸F]F-FES and multiple bone recurrence metastases of an ILBC, occured 5 years after surgery (SBRII, 15 mm, ER 80%, PR 80%, Ki67 40%, HER2 negative), radiotherapy and hormonotherapy with letrozole.