Hendris Wongso
1,2* 
, Ahmad Kurniawan
1, Yanuar Setiadi
3, Crhisterra E. Kusumaningrum
1, Eva M. Widyasari
1, Teguh H.A. Wibawa
1, Isa Mahendra
1,2, Muhamad B. Febrian
1, Maula E. Sriyani
1, Iim Halimah
1, Isti Daruwati
1,2,4, Rudi Gunawan
1,2,4, Arifudin Achmad
2,5,6, Dwianto H. Nugraha
7, Ronny Lesmana
8,9,10, Ari S. Nugraha
11,121 Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency Republic of Indonesia, Puspiptek, Banten 15314, Indonesia
2 Research Collaboration Center for Theranostic Radiopharmaceuticals, National Research and Innovation Agency, Jl. Ir. Soekarno KM 21, Jatinangor 45363, Indonesia
3 Research Center for Environmental and Clean Technology, Research Organization for Life Sciences and Environment, National Research and Innovation Agency, Puspiptek, Banten 15314, Indonesia
4 Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Ir. Soekarno KM 21, Jatinangor 45363, Indonesia
5 Department of Nuclear Medicine and Molecular Theranostics, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161
6 Oncology and Stem Cells Working Group, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161
7 Technology Development Division, PT. Kalbe Farma, Jakarta, Indonesia
8 Department of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, Jatinangor 45363, Indonesia
9 Physiology Molecular, Division of Biological Activity, Central Laboratory, Universitas Padjadjaran, Jatinangor 45363, Indonesia
10 Laboratory of Sciences, Graduate School, Universitas Padjadjaran, Bandung, Indonesia
11 Drug Utilisation and Discovery Research Group, Faculty of Pharmacy, Universitas Jember, Jember 68121, Indonesia
12 School of Chemistry and Molecular Biosciences, Molecular Horizons, University of Wollongong, Wollongong, New South Wales, 2522, Australia
Abstract
The translocator protein 18-kDa (TSPO) is a mitochondrial membrane protein that is previously identified as the peripheral benzodiazepine receptor (PBR). Furthermore, it plays a significant role in a diverse range of biochemical processes, including steroidogenesis, mitochondrial cholesterol transport, cell survival and death, cell proliferation, and carcinogenesis. Several investigations also reported its roles in various types of cancers, including colorectal, brain, breast, prostate, and lung cancers, as well as melanoma. According to a previous study, the expression of TSPO was upregulated in cancer cells, which corresponds to an aggressive phenotype and/or poor prognosis. Consequently, the potential for crafting diagnostic and prognostic tools with a focus on TSPO holds great potential. In this context, several radioligands designed to target this protein have been identified, and some of the candidates have advanced to clinical trials. In recent years, the use of hybrid probes with radioactive and fluorescence molecules for image-guided surgery has exhibited promising results in animal and human studies. This indicates that the approach can serve as a valuable surgical navigator during cancer surgery. The current hybrid probes are built from various molecular platforms, including small molecules, nanoparticles, and antibodies. Although several TSPO-targeted imaging probes have been developed, their development for image-guided surgery of cancers is still limited. Therefore, this review aims to highlight recent findings on the involvement of TSPO in carcinogenesis, as well as provide a new perspective on the potential application of TSPO-targeted hybrid probes for image-guided surgery.