Evaluation of a Neurokinin-1 Receptor–Targeted Technetium-99m Conjugate for Neuroendocrine Cancer Imaging

Kanduluru, Ananda Kumar; Srinivasarao, Madduri; Wayua, Charity

doi:10.1007/s11307-019-01391-w

Cited by 4 publications

(2 citation statements)

References 33 publications

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“…This combination therapy could be a universal and novel antitumor strategy exerting a dual action: a synergic anticancer action and protection from the severe side effects of chemotherapy and radiotherapy. In summary, NK-1R is an anticancer therapeutic target that could improve both the diagnosis and treatment of cancers [164,165]. The currently available data support the reprofiling of the antiemetic Aprepitant as an anticancer drug.…”

Section: Discussionmentioning

confidence: 89%

The Repurposing of Non-Peptide Neurokinin-1 Receptor Antagonists as Antitumor Drugs: An Urgent Challenge for Aprepitant

Coveñas,

Rodríguez,

Robinson

et al. 2023

IJMS

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The substance P (SP)/neurokinin-1 receptor (NK-1R) system is involved in cancer progression. NK-1R, activated by SP, promotes tumor cell proliferation and migration, angiogenesis, the Warburg effect, and the prevention of apoptosis. Tumor cells overexpress NK-1R, which influences their viability. A typical specific anticancer strategy using NK-1R antagonists, irrespective of the tumor type, is possible because these antagonists block all the effects mentioned above mediated by SP on cancer cells. This review will update the information regarding using NK-1R antagonists, particularly Aprepitant, as an anticancer drug. Aprepitant shows a broad-spectrum anticancer effect against many tumor types. Aprepitant alone or in combination therapy with radiotherapy or chemotherapy could reduce the sequelae and increase the cure rate and quality of life of patients with cancer. Current data open the door to new cancer research aimed at antitumor therapeutic strategies using Aprepitant. To achieve this goal, reprofiling the antiemetic Aprepitant as an anticancer drug is urgently needed.

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Section: Discussionmentioning

confidence: 89%

The Repurposing of Non-Peptide Neurokinin-1 Receptor Antagonists as Antitumor Drugs: An Urgent Challenge for Aprepitant

Coveñas,

Rodríguez,

Robinson

et al. 2023

IJMS

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“…Over the last few years, a significant increase of the interest in small molecular antagonists of neurokinin-1 receptor (NK1R) in terms of oncological applications can be observed. Some reports indicate new perspectives for the use of aprepitant [ 1 ] and of other NK1R antagonists [ 2 , 3 , 4 ] as vectors for selective radiopharmaceutical agents for NK1R-positive tumors.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Biological Evaluation of Aprepitant Based 177Lu-Radioconjugates

et al. 2022

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Currently, the search for promising NK1R-positive tumor-targeting radiopharmaceuticals based on the structure of small molecular antagonists of neurokinin-1 receptor can be observed. Following this trend, we continued our evaluation of aprepitant-based 177Lu-radioconjugates in terms of future oncological applications. For this purpose, three novel aprepitant homologues were synthesized to broaden the previously obtained derivative portfolio, functionalized with the DOTA chelator and labeled with 68Ga and 177Lu. The newly evaluated radioconjugates showed the intended significant increase in lipophilicity compared to the previous ones, while maintaining stability in the human serum. Then, in a receptor binding study to the human NK1 receptor, we compared the two series of 177Lu-radioconjugates of aprepitant with each other and with the reference Substance P derivative currently used in glioblastoma therapy, clearly indicating the high affinity and better binding capacity of the novel radioconjugates. The in vitro experimental results included in the presented study, supported by labeling optimization, radioconjugate characterization and docking modeling of new aprepitant-derived radioagents, confirm our assumptions about the usefulness of aprepitant as a NK1R targeting vector and point out the perspectives for the forthcoming first in vivo trials.

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