7.2

Conventional Treatment Regimes

Cytotoxic systemic chemotherapy and external beam radiation therapy have long

been at the forefront of treating cancers. As an example, the majority of the approved

therapies in metastatic castration-resistant prostate cancer that have significant

survival benefits are next-generation anti-hormonal therapies such as abiraterone

and enzalutamide, chemotherapeutic agents such as docetaxel and cabazitaxel, and

radiation therapy in the form of external beam or brachytherapies (Nuhn et al. 2019).

The introduction of ²²³Ra which conferred not only palliation of metastatic osseous

pain, but associated survival benefits as well, led the way for molecular-targeted

endoradiotherapies.

The studies evaluating prostate-specific membrane antigen (PSMA) as a

theranostic target in prostate cancer brought about a revolution in both disease

detection and therapy. Starting with monoclonal antibodies, and later with small

and mostly urea-based PSMA inhibitors, the targeting of PSMA has expanded

significantly (Vahidfar et al. 2019; Deb et al. 1996). The data on efficacy and safety

of PSMA-based radioligand therapies continues to provide solid evidence for their

introduction

in

the

management

algorithm

of

metastatic

prostate

cancer

(Ahmadzadehfar et al. 2015, 2020; Heck et al. 2019; Kratochwil et al. 2015;

Satapathy et al. 2021; Santoni et al. 2014). A multi-center analysis of chemother-

apy-naïve mCRPC patients undergoing ¹⁷⁷Lu-PSMA-based radioligand therapy

showed a significantly better overall survival in comparison to those that had

undergone prior chemotherapies (Ahmadzadehfar et al. 2020).

7.3

Targeted Therapy

18F-FDG, the ubiquitous molecule for PET imaging, targets glucose metabolism and

is used for various oncologic and non-oncologic applications (Parihar et al.

2018a, b, c, d, e; Jain et al. 2018; Moadel et al. 2003); however, its non-specificity

for tumor cells and the lack of a theranostic pair prompted the development of new

ligands with greater tumor specificity and availability of suitable radionuclide

theranostic pairs.

Targeted theranostics, when coupled with suitable indications and adequate

preselection of patients among other parameters, have proven to be safe and effective

in majority of cases (Ahmadzadehfar 2016; Baum and Kulkarni 2012; Kwekkeboom

et al. 2008; Strosberg et al. 2017). The safety and efficacy of peptide receptor

radionuclide

therapy

(PRRT)

in

neuroendocrine

tumors

and

PSMA-based

radioligand therapy (RLT) have been prospectively confirmed in multiple large-

scale studies, even with multiple therapy cycles (Yordanova et al. 2017a, b, c;

Ahmadzadehfar et al. 2016).

Nuclear medicine-led theranostics have proven valuable in several malignancies.

Neuroendocrine neoplasms—NENs (e.g., pheochromocytoma, paragangliomas,

neuroblastoma, gastro-entero-pancreatic NENs, pulmonary NENs, etc.)—have

been at the center of fruitful research for a long time (French et al. 2013; Matthay

et al. 2007; Yanik et al. 2015; Yordanova et al. 2017a, c; Baum et al. 2008;

7

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