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Phase I clinical ev...
Phase I clinical evaluation of 99mTc-labeled Affibody molecule for imaging HER2 expression in breast cancer
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- Bragina, Olga (author)
- Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Therapy & Diagnost, Tomsk, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia.
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- Chernov, Vladimir (author)
- Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Therapy & Diagnost, Tomsk, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia.
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- Larkina, Mariia (author)
- Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia.;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia.
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- Rybina, Anstasiya (author)
- Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Therapy & Diagnost, Tomsk, Russia.
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- Zelchan, Roman (author)
- Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Therapy & Diagnost, Tomsk, Russia.;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia.
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- Garbukov, Eugeniy (author)
- Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Therapy & Diagnost, Tomsk, Russia.
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- Oroujeni, Maryam, PhD, 1982- (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Affibody AB, Solna, Sweden.
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- Loftenius, Annika (author)
- Affibody AB, Solna, Sweden.
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- Orlova, Anna, 1960- (author)
- Uppsala universitet,Institutionen för läkemedelskemi
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- Sörensen, Jens (author)
- Uppsala universitet,Radiologi
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- Frejd, Fredrik Y. (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Affibody AB, Solna, Sweden.
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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Russian Acad Sci, Canc Res Inst, Tomsk Natl Res Med Ctr, Dept Nucl Therapy & Diagnost, Tomsk, Russia;Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia. Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Res Ctr Oncotheranost, Tomsk, Russia.;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia. (creator_code:org_t)
- Ivyspring International Publisher, 2023
- 2023
- English.
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In: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 13:14, s. 4858-4871
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Abstract
Subject headings
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- The determination of tumor human epidermal growth factor receptor type 2 (HER2) status is of increasing importance with the recent approval of more efficacious HER2-targeted treatments. There is a lack of suitable methods for clinical in vivo HER2 expression assessment. Affibody molecules are small affinity proteins ideal for imaging detection of receptors, which are engineered using a small (molecular weight 6.5 kDa) nonimmunoglobulin scaffold. Labeling of Affibody molecules with positron emitters enabled the development of sensitive and specific agents for molecular imaging. The development of probes for SPECT would permit the use of Affibody-based imaging in regions where PET is not available. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the Tc-99m-ZHER2:41071 Affibody molecule developed for SPECT/CT imaging of HER2 expression.Methods: Thirty-one patients with primary breast cancer were enrolled and divided into three cohorts (injected with 500, 1000, or 1500 mu g ZHER2:41071) comprising at least five patients with high (positive) HER2 tumor expression (IHC score 3+ or 2+ and ISH positive) and five patients with low (IHC score 2+ or 1+ and ISH negative) or absent HER2 tumor expression. Patients were injected with 451 +/- 71 MBq Tc-99m-ZHER2:4107. Planar scintigraphy was performed after 2, 4, 6 and 24 h, and SPECT/CT imaging followed planar imaging 2, 4 and 6 h after injection.Results: Injections of Tc-99m-ZHER2:41071 were well tolerated and not associated with adverse events. Normal organs with the highest accumulation were the kidney and liver. The effective dose was 0.019 +/- 0.004 mSv/MBq. Injection of 1000 mu g provided the best standard discrimination between HER2-positive and HER2-low or HER2-negative tumors 2 h after injection (SUVmax 16.9 +/- 7.6 vs. 3.6 +/- 1.4, p < 0.005). The Tc-99m-ZHER2:41071 uptake in HER2-positive lymph node metastases (SUVmax 6.9 +/- 2.4, n = 5) was significantly (p < 0.05) higher than that in HER2-low/negative lymph nodes (SUVmax 3.5 +/- 1.2, n = 4). Tc-99m-ZHER2:41071 visualized hepatic metastases in a patient with liver involvement.Conclusions: Injections of Tc-99m-ZHER2:41071 appear safe and exhibit favorable dosimetry. The protein dose of 1000 mu g provides the best discrimination between HER2-positive and HER2-low/negative expression of HER2 according to the definition used for current HER2-targeting drugs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- HER2
- Affibody
- Tc-99m
- ZHER2
- 41071
- SPECT
- Phase I
Publication and Content Type
- ref (subject category)
- art (subject category)
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Bragina, Olga
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Chernov, Vladimi ...
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Larkina, Mariia
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Rybina, Anstasiy ...
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Zelchan, Roman
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Garbukov, Eugeni ...
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Oroujeni, Maryam ...
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Loftenius, Annik ...
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Orlova, Anna, 19 ...
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Sörensen, Jens
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Frejd, Fredrik Y ...
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Tolmachev, Vladi ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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- Articles in the publication
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Theranostics
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Uppsala University