Preclinical positron emission computed tomography of prolonged tumor growth after lutetium-177 prostate-specific membrane antigen treatment in xenograft model of human prostate cancer

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Abstract

BACKGROUND: New treatment methods of castration-resistant prostate cancer with radionuclide therapy are needed. They will optimize personalized strategy for radionuclide therapy of metastatic castrate-resistant prostate cancer using low molecular weight ligands to prostate-specific membrane antigen (PSMA) labeled with lutetium-177.

AIM: To define the long-term effects and effectiveness of the treatment experimental animals with PET imaging to refine the research strategy.

METHODS: The study was performed in nu/nu male mice with PSMA-expressing 22Rv1 prostate cancer xenografts. Positron emission computed tomography with 18F-PSMA-1007 was used to confirm the tumor regrowth after a single therapeutic dose of [177Lu]Lu-PSMA-I&T.

RESULTS: Positron emission tomography imaging with 18F-PSMA-1007 showed the possibility of prolonged 22Rv1 tumor regrowth after a single injection of 9.2 MBq of [177Lu]Lu-PSMA-I&T, which is equivalent to minimal human therapeutic dose (28.6 MBq/kg).

CONCLUSIONS: The study confirmed the short period of the observed therapeutic effect after a single injection of 9.2 MBq of [177Lu]Lu-PSMA-I&T. The tumor regrowth in 2.5 months after the reduction of 22Rv1 xenografts to a non-palpable state was confirmed by positron emission computed tomography with 18F-PSMA-1007. These results confirm the need to study the frequency of repeated administrations of radiopharmaceuticals based on ligands to PSMA labeled with lutetium-177 to achieve a stable therapeutic effect in cases where a single dose reduction is necessary.

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About the authors

Olga E. Klementyeva

N.N. Blokhin National Medical Research Center of Oncology

Email: klementyeva.olga@gmail.com
ORCID iD: 0000-0002-6604-0860
SPIN-code: 6653-1201

Cand. Sci. (Bio.)

Russian Federation, 23 Kashirskoe shosse, 115478 Moscow

Alexey A. Lipengolts

N.N. Blokhin National Medical Research Center of Oncology

Email: lipengolts@mail.ru
ORCID iD: 0000-0002-5631-9016

Cand. Sci. (Phys., Math.), Senior Research Associate

Russian Federation, 23 Kashirskoe shosse, 115478 Moscow

Elena Y. Grigorieva

N.N. Blokhin National Medical Research Center of Oncology

Email: grig-elen11@mail.ru
ORCID iD: 0000-0001-7726-7991

Dr. Sci. (Bio.)

Russian Federation, 23 Kashirskoe shosse, 115478 Moscow

Anna V. Smirnova

N.N. Blokhin National Medical Research Center of Oncology; Moscow Clinical Scientific Center n.a. A.S. Loginov

Email: smirn-ova@mail.ru
ORCID iD: 0000-0003-0386-9732
SPIN-code: 4663-3199

Cand.  Sci. (Bio.), Senior Research Associate

Russian Federation, 23 Kashirskoe shosse, 115478 Moscow; Moscow

Yulia A. Finogenova

N.N. Blokhin National Medical Research Center of Oncology; Peoples’ Friendship University of Russia

Author for correspondence.
Email: b-f.finogenova@yandex.ru
ORCID iD: 0000-0002-5144-1039
SPIN-code: 7597-2604

Research Associate

Russian Federation, 23 Kashirskoe shosse, 115478 Moscow; Moscow

Kristina E. Shpakova

N.N. Blokhin National Medical Research Center of Oncology

Email: shpakova.k.e@gmail.com
ORCID iD: 0000-0003-0246-1794
Russian Federation, 23 Kashirskoe shosse, 115478 Moscow

Vsevolod A. Skribitsky

N.N. Blokhin National Medical Research Center of Oncology

Email: skvseva@yandex.ru
ORCID iD: 0000-0003-2942-7895
SPIN-code: 8568-6890

Junior Research Associate

Russian Federation, 23 Kashirskoe shosse, 115478 Moscow

Yulia S. Lagodzinskaya

N.N. Blokhin National Medical Research Center of Oncology

Email: ishtar.lynx@gmail.com
ORCID iD: 0000-0001-6260-0763
SPIN-code: 3374-7453
Russian Federation, 23 Kashirskoe shosse, 115478 Moscow

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2. Fig. 1. Nu/nu male mouse with 22Rw1, taken after 2.5 months of treatment with [177Lu]Lu-PSMA I&T (9.2 MBq).

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3. Fig. 2. Positron emission tomography scans of a mouse with prolonged growth of 22Rv1 tumor: a — 55 min after radiopharmaceutical administration; b — after 2.5 h; c — after 3 h. In the circle — tumor 22Rv1. Arrow — hyperfixation of radiopharmaceutical 18F-PSMA-1007 in tumor metastatic area.

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