Page 24 - ARNM-1-2

Advances in Radiotherapy
& Nuclear Medicine FAP-targeted RLT in cancer

drugs have undergone testing, only a few pre-clinical et al. conducted a study involving Ga-FAPI PET/CT to
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studies have shown improved outcomes, and the efficacy of diagnose primary and metastatic lesions in 74 patients
these drugs in clinical trials has been limited. The current with 12 different tumor types, comparing it with F-FDG
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status of targeting FAP for anti-CAF therapy remains at an PET/CT . Their findings demonstrated that Ga-FAPI
[10]
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early clinical trial stage . Table 1 summarizes the different PET/CT excelled in identifying malignancies, boasting
[25]
non-radionuclide-targeted therapeutic strategies against favorable TBR, and outperformed F-FDG PET/CT in
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FAP available from clinicaltrials.gov. diagnosing primary and metastatic lesions. Pang et al.
also explored the usefulness of Ga-FAP-2286 PET/CT in
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3. FAP-targeted RLT as an antitumor imaging various malignancies, conducting a comparative
therapy approach analysis with 18 F-FDG and 68 Ga-FAPI-46 PET/CT .
[28]
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In recent years, multiple small-molecule FAPIs and cyclic Their results indicated that Ga-FAP-2286 may offer a
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peptides targeting FAP (FAP-2286) have been designed superior alternative to F-FDG, particularly for cancer
18
for imaging purposes, facilitating the visualization types characterized by low-to-moderate F-FDG uptake,
of the tumor stroma (labeled with Ga, F, or 99m Tc). including gastric, pancreatic, and hepatic cancers. In
18
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Multiple studies have reported on the tumor uptake and addition, 68 Ga-FAP-2286 demonstrated longer tumor
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biodistribution of FAPIs/FAP-2286 [9,26,27] . For instance, retention than Ga-FAPI-46 at later time points. Figure 1
Kratochwil et al. conducted an evaluation involving shows the representative PET images of 7 patients with
80 patients with 28 different tumor entities (54 primary diverse tumor types who underwent 18 F-FDG PET,
tumors and 229 metastases). This evaluation employed 68 Ga-FAPI-46 PET, and Ga-FAP-2286 PET imaging in a
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68 Ga-FAPI positron emission tomography/computed week or less. These results suggest that 68Ga-FAP-2286 is
tomography (PET/CT) . The results revealed that a promising candidate for pan-tumor TRT. Consequently,
[9]
esophageal, breast, cholangiocarcinoma, sarcoma, and therapeutic radionuclides labeled with FAPI, peptides,
lung cancers exhibited higher Ga-FAPI uptake, leading and small-molecule radioconjugates targeting FAP have
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to elevated tumor-to-background ratios (TBR). Chen gained popularity in pre-clinical and clinical antitumor
Table 1. Summary of trials of non‑radionuclide targeted therapeutic strategies against fibroblast activation protein (FAP)
Trial registration no. and Phase Type of tumor Study start Study Enrollment
medicine completion
NCT03932565: Enfortumab Phase 1 Nectin4-positive advanced February 13 December 31 30 (estimated)
Vedotin malignant solid tumor 2019 (actual) 2021 (estimated)
NCT01722149: Adoptively Early phase 1 Malignant pleural February 19 July 18 2019 4 (estimated)
transferred FAP-specific CD8 mesothelioma with pleural 2015 (actual) (estimated)
positive re-directed T cells effusion
NCT05098405: MP0317 Phase 1 Relapsed/refractory October 11 2021 2024 – 2004 78 (estimated)
advanced solid tumors (actual) (estimated)
NCT04969835: AVA6000 Phase 1 Locally advanced July 16 2021 June 30 2023 80 (estimated)
(unresectable) and/or (actual) (estimated)
metastatic solid tumors
NCT02558140: RO6874813 Phase 1 Locally advanced or October 11 2015 November 06 120 (actual)
metastatic solid tumors (actual) 2017 (actual)
NCT04857138: RO7300490 Phase 1 Advanced and/or metastatic May 18 2021 August 17 2026 280 (estimated)
solid tumor (actual) (estimated)
NCT03875079: RO6874281 Phase 1 Advanced or metastatic June 24 2019 July 14 2022 83 (actual)
melanoma (actual) (actual)
NCT04826003: RO7122290 Phase 1, Phase 2 Previously treated, July 14 2021 July 31 2025 80 (estimated)
metastatic, (actual) (estimated)
microsatellite-stable
colorectal adenocarcinoma
with high CEACAM5
expression
NCT03386721:RO6874281 Phase 2 Advanced and/or metastatic February 19 December 30 256 (actual)
solid tumors 2018 (actual) 2021 (actual)

Volume 1 Issue 2 (2023) 3 https://doi.org/10.36922/arnm.1667