Phase I Study of <sup>99m</sup>Tc-ADAPT6, a Scaffold Protein–Based Probe for Visualization of HER2 Expression in Breast Cancer

Bragina, Olga; Witting, Emma von; Garousi, Javad; Zelchan, Roman; Sandström, Mattias; Orlova, Anna; Медведева, А. А.; Дорошенко, А. В.; Vorobyeva, Anzhelika; Lindbo, Sarah; Borin, Jesper; Tarabanovskaya, Natalya; Sörensen, Jens; Hober, Sophia; Chernov, Vladimir; Tolmachev, Vladimir

doi:10.2967/jnumed.120.248799

Cited by 51 publications

(54 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Одним из представителей альтернативных каркасных являются ADAPT6, представляющие собой альбумин-связывающие домены стрептококкового протеина G и имеющие небольшие размеры (46-59 аминокислотных остатков, молекулярная масса 5-7 кДа). На этапе доклинических исследований было продемонстрировано, что меченный различными радионуклидами ADAPT6 показывает высокоe контрастное изображение Her2-позитивных опухолей у ксенографтов мышей всего через несколько часов после введения [18,19].…”

Section: __________________________unclassified

Possibilities of radionuclide diagnostics of Her2-positive breast cancer using technetium-99m-labeled target molecules: the first experience of clinical use

et al. 2021

View full text Add to dashboard Cite

РЕЗЮМЕАктуальность. Главной целью определения статуса Her2/neu в клинической практике прежде всего является измерение показаний для назначения таргетной терапии. Основными методами выявления статуса Her2/neu являются иммуногистохимический метод и флуоресцентная гибридизация in situ (FISH). Несмотря на распространенность, они имеют ряд существенных недостатков. В течение последних нескольких лет большое распространение приобретает радионуклидная диагностика с использованием нового класса альтернативных каркасных белков, отвечающих всем требованиям для оптимальной доставки радионуклида к опухолевым клеткам.Цель. Изучение возможности клинического использования радиофармацевтического препарата на основе меченных технецием-99m адресных молекул для диагностики рака молочной железы с гиперэкспрессией Her2/neu у человека. Материалы и методы. В исследование включены 11 больных раком молочной железы (T 1-4 N 0-2 M 0 ) до проведения системной терапии: пять человек с гиперэкспрессией Her2/neu; у шестерых экспрессия маркера выявлена не была. Во всех случаях выполнялось морфологическое и иммуногистохимическое исследование. При наличии значения Her2/neu 2+ проводился FISH-анализ. Препарат готовился непосредственно перед манипуляцией, после чего медленно внутривенно вводился пациенту. Сцинтиграфические исследования в режиме WholeBody и однофотонная эмиссионная компьютерная томография органов грудной клетки выполнялись через 2, 4, 6 и 24 ч после введения.

show abstract

Section: __________________________unclassified

Possibilities of radionuclide diagnostics of Her2-positive breast cancer using technetium-99m-labeled target molecules: the first experience of clinical use

et al. 2021

View full text Add to dashboard Cite

show abstract

“…An evaluation of absorbed doses for humans demonstrated very favourable dosimetry with an effective dose of 0.00066 mSv/MBq ( Table 5 ). For comparison, the effective dose for 111 In-trastuzumab was 0.19 ± 0.02 mSv/MBq [ 35 ], for 99m Tc-labelled scaffold protein ADAPT6 0.010 ± 0.003 mSv/MBq [ 36 ], and for 68 Ga-labelled anti-HER2 Affibody molecule ABY-025 0.030 ± 0.003 mSv/MBq [ 21 ]. To a high extent, this was determined by low retention of activity in liver and kidneys as well as a short residence time in the whole body.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake

Oroujeni

Rinne

Vorobyeva

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [99mTc]Tc-ZHER2:V2 and [99mTc]Tc-ZHER2:2395. [99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99mTc using a GGGC chelator. The new probe, [99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.

show abstract

“…It has been demonstrated that the response strongly correlates with the grade [38]. It has been shown that tumor-to-spleen uptake ratio for 111 In and 68 Ga-labeled affibody molecules [40] and tumor-to-contralateral breast ratio for 99m Tc-labeled ADAPT6 [41] correlates strongly with the level of HER2 expression in breast cancer. Alternatively, the uptake of an imaging probe in tumor might be quantified using PET and correlated with expression level [42].…”

Section: Discussionmentioning

confidence: 99%

Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1

et al. 2020

Self Cite

View full text Add to dashboard Cite

Efficient treatment of disseminated triple-negative breast cancer (TNBC) remains an unmet clinical need. The epithelial cell adhesion molecule (EpCAM) is often overexpressed on the surface of TNBC cells, which makes EpCAM a potential therapeutic target. Radionuclide molecular imaging of EpCAM expression might permit selection of patients for EpCAM-targeting therapies. In this study, we evaluated a scaffold protein, designed ankyrin repeat protein (DARPin) Ec1, for imaging of EpCAM in TNBC. DARPin Ec1 was labeled with a non-residualizing [125I]I-para-iodobenzoate (PIB) label and a residualizing [99mTc]Tc(CO)3 label. Both imaging probes retained high binding specificity and affinity to EpCAM-expressing MDA-MB-468 TNBC cells after labeling. Internalization studies showed that Ec1 was retained on the surface of MDA-MB-468 cells to a high degree up to 24 h. Biodistribution in Balb/c nu/nu mice bearing MDA-MB-468 xenografts demonstrated specific uptake of both [125I]I-PIB-Ec1 and [99mTc]Tc(CO)3-Ec1 in TNBC tumors. [125I]I-PIB-Ec1 had appreciably lower uptake in normal organs compared with [99mTc]Tc(CO)3-Ec1, which resulted in significantly (p < 0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by micro-Single-Photon Emission Computed Tomography/Computed Tomography (microSPECT/CT) imaging. In conclusion, an indirectly radioiodinated Ec1 is the preferable probe for imaging of EpCAM in TNBC.

show abstract

Phase I Study of ^99mTc-ADAPT6, a Scaffold Protein–Based Probe for Visualization of HER2 Expression in Breast Cancer

Cited by 51 publications

References 23 publications

Possibilities of radionuclide diagnostics of Her2-positive breast cancer using technetium-99m-labeled target molecules: the first experience of clinical use

Possibilities of radionuclide diagnostics of Her2-positive breast cancer using technetium-99m-labeled target molecules: the first experience of clinical use

Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake

Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1

Contact Info

Product

Resources

About

Phase I Study of 99mTc-ADAPT6, a Scaffold Protein–Based Probe for Visualization of HER2 Expression in Breast Cancer

Cited by 51 publications

References 23 publications

Possibilities of radionuclide diagnostics of Her2-positive breast cancer using technetium-99m-labeled target molecules: the first experience of clinical use

Possibilities of radionuclide diagnostics of Her2-positive breast cancer using technetium-99m-labeled target molecules: the first experience of clinical use

Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake

Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1

Contact Info

Product

Resources

About

Phase I Study of ^99mTc-ADAPT6, a Scaffold Protein–Based Probe for Visualization of HER2 Expression in Breast Cancer