Direct in Vivo Comparison of <sup>99m</sup>Tc-labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy
Non-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) can provide stratifcation of patients for HER2-targeting therapy. This method can also enable monitoring of the response to such therapies and thereby the treatment will be more personalized and efficient. Phase I clinical evaluation of two scaffold protein-based imaging probes, [99mTc]Tc-(HE)3-G3 and [99mTc]Tc-ADAPT6, demonstrated that their injections are safe, well-tolerated and cause low level of absorbed and equivalent doses. The goal of this preclinical study was to select the best probe for patients&rsquo; stratification and for response monitoring. Biodis-tribution of both tracers was compared in mice bearing SKOV-3 xenografts with high HER2 ex-pression and MDA-MB-468 xenografts with very low expression. Changes in accumulation of both probes in SKOV-3 tumors 24 h after injection of trastuzumab were evaluated. Both [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 permitted high contrast imaging of HER2-expressing tumors and clear discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-ADAPT6 has better preconditions for higher sensitivity and specificity of stratification. On the other hand, [99mTc]Tc-(HE)3-G3 is capable to sense the decrease of HER2 expression on re-sponse to trastuzumab therapy only 24 h after injection of loading dose. This indicates that this tracer would be better for monitoring early response to such treatment. Results of this study should be considered in planning of further clinical development of HER2 imaging probes..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Preprints.org - (2022) vom: 08. Dez. Zur Gesamtaufnahme - year:2022 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tolmachev, Vladimir [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| doi: |
10.20944/preprints202211.0188.v1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
preprintsorg037839772 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | preprintsorg037839772 | ||
| 003 | DE-627 | ||
| 005 | 20230429203934.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 221111s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.20944/preprints202211.0188.v1 |2 doi | |
| 024 | 7 | |a 10.20944/preprints202211.0188.v1 |2 doi | |
| 035 | |a (DE-627)preprintsorg037839772 | ||
| 035 | |a (preprintsorg)10.20944/preprints202211.0188 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tolmachev, Vladimir |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Direct in Vivo Comparison of <sup>99m</sup>Tc-labeled Scaffold Proteins, DARPin G3 and ADAPT6, for Visualization of HER2 Expression and Monitoring of Early Response for Trastuzumab Therapy |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Non-invasive radionuclide molecular visualization of human epidermal growth factor receptor type 2 (HER2) can provide stratifcation of patients for HER2-targeting therapy. This method can also enable monitoring of the response to such therapies and thereby the treatment will be more personalized and efficient. Phase I clinical evaluation of two scaffold protein-based imaging probes, [99mTc]Tc-(HE)3-G3 and [99mTc]Tc-ADAPT6, demonstrated that their injections are safe, well-tolerated and cause low level of absorbed and equivalent doses. The goal of this preclinical study was to select the best probe for patients&rsquo; stratification and for response monitoring. Biodis-tribution of both tracers was compared in mice bearing SKOV-3 xenografts with high HER2 ex-pression and MDA-MB-468 xenografts with very low expression. Changes in accumulation of both probes in SKOV-3 tumors 24 h after injection of trastuzumab were evaluated. Both [99mTc]Tc-ADAPT6 and [99mTc]Tc-(HE)3-G3 permitted high contrast imaging of HER2-expressing tumors and clear discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-ADAPT6 has better preconditions for higher sensitivity and specificity of stratification. On the other hand, [99mTc]Tc-(HE)3-G3 is capable to sense the decrease of HER2 expression on re-sponse to trastuzumab therapy only 24 h after injection of loading dose. This indicates that this tracer would be better for monitoring early response to such treatment. Results of this study should be considered in planning of further clinical development of HER2 imaging probes. | ||
| 650 | 4 | |a Medicine & Pharmacology | |
| 650 | 4 | |a 610 | |
| 700 | 1 | |a Bodenko, Vitalina |e verfasserin |4 aut | |
| 700 | 1 | |a Oroujeni, Maryam |e verfasserin |4 aut | |
| 700 | 1 | |a Deyev, Sergey |e verfasserin |4 aut | |
| 700 | 1 | |a Konovalova, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Schulga, Alexey |e verfasserin |4 aut | |
| 700 | 1 | |a Lindbo, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Hober, Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Bragina, Olga |e verfasserin |4 aut | |
| 700 | 1 | |a Orlova, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Vorobyeva, Anzhelika |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Preprints.org |g (2022) vom: 08. Dez. |
| 773 | 1 | 8 | |g year:2022 |g day:08 |g month:12 |
| 856 | 4 | 0 | |u https://doi.org/10.3390/ijms232315181 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.20944/preprints202211.0188.v1 |z kostenfrei |3 Volltext |
| 912 | |a preprintsorg | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2022 |b 08 |c 12 | ||