Emerging Radiopharmaceuticals Beyond FDG for Ovarian Cancer: A Review of Advances in Nuclear Medicine

Abstract

Aims: This review summarizes the role and future prospects of nuclear medicine in ovarian cancer, focusing on novel radiopharmaceuticals beyond FDG for diagnostic, predictive, and therapeutic applications within a theranostic framework.

Materials and methods: A narrative literature review was conducted using major databases. Peer-reviewed articles addressing non-FDG radiopharmaceuticals in ovarian cancer were identified and assessed; FDG-based studies were excluded due to the availability of prior comprehensive reviews.

Results: Novel radiopharmaceuticals show potential to enhance diagnostic accuracy, allow early evaluation of treatment response, predict chemotherapy resistance, and support stratification for targeted therapies. Several tracers are under investigation for theranostic use, offering combined diagnostic and therapeutic benefits.

Discussion: Incorporating novel radiopharmaceuticals into ovarian cancer management may help overcome limitations of conventional imaging and systemic therapy. Theranostic strategies, uniting molecular imaging with radionuclide therapy, represent a promising step toward personalized medicine and could significantly influence clinical outcomes.

Conclusion: Nuclear medicine, through innovative radiopharmaceuticals and theranostic approaches beyond FDG, is expected to expand its role in ovarian cancer care. Further research is needed to validate these applications and facilitate their integration into clinical practice.

Keywords: diagnostic imaging; nuclear medicine; ovarian neoplasms; positron emission tomography; precision medicine; radionuclide imaging.

FIGURE 1

Schematic overview of the radiopharmaceuticals that are mentioned in this review. The radiopharmaceutical is administered through intravenous injection, where it enters the blood stream and attaches to its binding site: The binding site can be located on the cell surface, within the nucleus or on a different cell type from the tumour microenvironment. CA125, carbohydrate antigen 125; CD13, aminopeptidase N; CTLs, choline transporter‐like proteins; CXCL12, C‐X‐C motif chemokine 12; CXCR4, C‐X‐C chemokine receptor 4; E2, oestradiol; FAP(I), fibroblast activation protein (inhibitor); FES, fluoro‐17β‐oestradiol; FLT, fluorothymidine; GPER, G protein‐coupled oestrogen receptor; HER2, human epidermal growth factor receptor 2; MUC16, mucin 16; NGR, asparagine‐glycine‐arginine; PARP(i), Poly(adenosine diphosphate‐ribose) polymerase (inhibitor); PSMA, prostate specific membrane antigen; RGD, arginylglycylaspartic acid; SLC43A2, solute carrier family 43 member 2; TK1, thymidine kinase 1; VEGF(R), vascular endothelial growth factor (receptor). Created in BioRender. Veenstra (2025) https://BioRender.com/s16u284.

FIGURE 2

PET/CT scan with [⁶⁸Ga]Ga‐PSMA‐11 in a 40‐year‐old woman. From Kunikowska et al. [44] (A) Maximum intensity projection, arrow indicates the lesion with abnormal tracer accumulation. (B) CT, arrow indicates the lesion in the right ovary. (C) Fusion PET/CT, arrow indicates the high tracer accumulation in the right ovary lesion visible on CT with SUV_max 13.8. Final histopathology revealed borderline ovarian tumour. Copyright 2022 Wolters Kluwer Health Inc. All rights reserved.

FIGURE 3

CXCR4‐directed positron emission tomography in several malignancies. From Werner et al. [51] Maximum intensity projections. The figure primarily demonstrates moderate to no uptake on CXCR4‐directed imaging (arrows), with the exception of the ovarian cancer patient, where the tumour masses display fairly high CXCR4 expression. (A) PDAC, pancreatic ductal adenocarcinoma; (B) PNET, pancreatic neuroendocrine tumour; (C) Ovarian cancer; (D) RCC, renal cell carcinoma; (E) PCa, prostate cancer. Copyright 2019 Werner, Kircher, Higuchi, Kircher, Schirbel, Wester, Buck, Pomper, Rowe and Lapa.

FIGURE 4

[¹⁸F]F‐FDG versus [⁶⁸Ga]Ga‐FAPI‐04 positron emission tomography. From Zheng et al. [58] A 35‐year‐old woman who previously underwent surgery for poorly differentiated mucinous ovarian adenocarcinoma. Fluorine‐18‐fluorodeoxyglucose (¹⁸F‐FDG) positron emission tomography/computed tomography (PET/CT) (a) and gallium‐68‐labelled fibroblast activation protein inhibitor (FAPI)‐04 PET/CT (b) demonstrate intense uptake in the right ilium (long arrow). ¹⁸F‐FDG PET/CT showed no abnormal uptake throughout the body, whilst ⁶⁸Ga‐FAPI PET/CT showed increased uptake in a cervical lymph node, the retroperitoneal lymph nodes, and the pelvic site of recurrence (bent arrow). Subsequent biopsy of the cervical node found metastatic ovarian serous carcinoma. Copyright 2022 The Author(s). Published by Wolters Kluwer Health Inc.

FIGURE 5

[¹⁸F]PARP1‐inhibitor and [¹⁸F]FDG PET/CT images of a patient with ovarian cancer with vaginal cuff lesion. From Makvandi et al. [65] [¹⁸F]FTT (left) is a [¹⁸F]PARP1‐inhibitor. Minimal radiotracer in the urinary bladder with [¹⁸F]PARP1‐inhibitor PET allowed for clear visualisation of the lesion (green arrow) with no interference, despite some bowel uptake (yellow arrow on [¹⁸F]PARP1‐inhibitor image). Note excreted radiotracer in the bladder on [¹⁸F]FDG PET (yellow arrow on [¹⁸F]FDG PET). Copyright 2018, American Society for Clinical Investigation.