7.5

Emerging Therapies

The emergence of radiotheranostics is based on the use of a single radionuclide or a

pair of radionuclides that can be labelled to a single targeting agent which can be

used for imaging and therapy. Essentially, what you see is what you treat, achieving

a personalized treatment approach.

Theranostics combines the practice of personalized and precision medicine and

requires a multi-disciplinary team of experts, primarily from the fields of nuclear

medicine, radiation oncology, medical and surgical oncology, and onco-pathology.

Additionally, based on the particular cancer site being managed, experts from

urology, gastroenterology, neurosurgery, pulmonology, etc. may be involved in

the decision-making process.

Fibroblast activation protein (FAP) is a protein that is overexpressed on the

cellular surface of the cancer-associated fibroblasts. FAP inhibitors (FAPI) have

recently been used in PET imaging of multiple malignancies. ⁶⁸Ga-FAPI PET/CT

was shown to have superior imaging characteristics with high tumor/background

ratios in around 28 different malignancies (Kratochwil et al. 2019). They showed

that primary malignancies of the esophagus, breast, lung, sarcomas, and

cholangiocarcinomas showed the highest avidity on ⁶⁸Ga-FAPI PET/CT. One of

the main advantages of the FAPI tracers is that they can be tagged with ¹⁷⁷Lu for

subsequent treatment of these malignancies.

Alpha-therapy has the advantage of depositing a high dose of radiation within a

short range, due to the high linear energy transfer of alpha particles in comparison to

beta-particles. Even though most studies on theranostics have been performed with

beta-emitters, commonly ¹⁷⁷Lu, ⁹⁰Y, and ¹³¹I, the success of alpha-therapy with

223Ra

in

mCRPC

prompted

exploration of alpha-agents

in

several other

malignancies as well (Kratochwil et al. 2014; Parker et al. 2013; Morgenstern

et al. 2018; Parihar et al. 2021). The main alpha-emitters including ²²⁵Ac, ²¹³Bi,

227Th, 211At, and 212Pb are being currently studied in hematologic and several solid

malignancies (Haberkorn et al. 2017; Targeted Alpha Therapy Working Group

2018). Presently, the major hindrances to the growth of alpha-therapy include its

high costs and availability that further limit the contribution to the scientific evidence

by only select well-equipped and resource-plenty institutes and countries.

PSMA ligands have been increasingly utilized in prostate cancer, for both

diagnosis and therapy. Another advantage of PSMA (Fig. 7.3) is that it can bind to

endothelial cells in the neovasculature which has been used for targeting extra-

prostatic malignancies (Parihar et al. 2018h, i, 2020b). This has both diagnostic as

well as novel theranostic applications. This is of special significance in malignancies

with extremely poor prognosis and limited overall survival with the current manage-

ment algorithms, such as aggressive sarcomas, glioblastoma multiforme, and

advanced pancreatic malignancies.

Melanocortin-1 receptor (MC1-R) is being studied as a theranostic target in

patients with melanoma. Preclinical models have shown high, selective uptake of

MC1-R targeting agents in metastatic melanoma disease sites (Miao and Quinn

2008). Further clinical studies can shed light on this interesting and potential

7

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