Abstract
Purpose: The study was undertaken to develop and evaluate the potential of an integrin a v b 6 -binding peptide (a v b 6 -BP) for noninvasive imaging of a diverse range of malignancies with PET. Experimental Design: The peptide a v b 6 -BP was prepared on solid phase and radiolabeled with 4-[ 18 F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired a v b 6 -expressing and a v b 6 -null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired a v b 6 -expressing and a v b 6 -null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer. Results: [ 18 F]a v b 6 -BP displayed excellent affinity and selectivity for the integrin a v b 6 in vitro [IC 50 (a v b 6 ) ¼ 1.2 nmol/L vs IC 50 (a v b 3 ) >10 mmol/L] in addition to rapid target-specific cell binding and internalization (72.5% 0.9% binding and 52.5% 1.8%, respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [ 18 F]a v b 6 -BP was rapid, primarily via the kidneys. In patients, [ 18 F]a v b 6 -BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [ 18 F]a v b 6 -BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung. Conclusions: The clinical impact of [ 18 F]a v b 6 -BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1206-1215 |
| Number of pages | 10 |
| Journal | Clinical Cancer Research |
| Volume | 25 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 15 2019 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Preclinical development and first-in-human imaging of the integrin a v b 6 with [ 18 F]a v b 6 -binding peptide in metastatic carcinoma . / Hausner, Sven H.; Bold, Richard J; Cheuy, Lina Y.; Chew, Helen K; Daly, Megan E; Davis, Ryan A.; Foster, Cameron C; Kim, Edward; Sutcliffe, Julie.
In: Clinical Cancer Research, Vol. 25, No. 4, 15.02.2019, p. 1206-1215.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Preclinical development and first-in-human imaging of the integrin a v b 6 with [ 18 F]a v b 6 -binding peptide in metastatic carcinoma
AU - Hausner, Sven H.
AU - Bold, Richard J
AU - Cheuy, Lina Y.
AU - Chew, Helen K
AU - Daly, Megan E
AU - Davis, Ryan A.
AU - Foster, Cameron C
AU - Kim, Edward
AU - Sutcliffe, Julie
PY - 2019/2/15
Y1 - 2019/2/15
N2 - Purpose: The study was undertaken to develop and evaluate the potential of an integrin a v b 6 -binding peptide (a v b 6 -BP) for noninvasive imaging of a diverse range of malignancies with PET. Experimental Design: The peptide a v b 6 -BP was prepared on solid phase and radiolabeled with 4-[ 18 F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired a v b 6 -expressing and a v b 6 -null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired a v b 6 -expressing and a v b 6 -null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer. Results: [ 18 F]a v b 6 -BP displayed excellent affinity and selectivity for the integrin a v b 6 in vitro [IC 50 (a v b 6 ) ¼ 1.2 nmol/L vs IC 50 (a v b 3 ) >10 mmol/L] in addition to rapid target-specific cell binding and internalization (72.5% 0.9% binding and 52.5% 1.8%, respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [ 18 F]a v b 6 -BP was rapid, primarily via the kidneys. In patients, [ 18 F]a v b 6 -BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [ 18 F]a v b 6 -BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung. Conclusions: The clinical impact of [ 18 F]a v b 6 -BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.
AB - Purpose: The study was undertaken to develop and evaluate the potential of an integrin a v b 6 -binding peptide (a v b 6 -BP) for noninvasive imaging of a diverse range of malignancies with PET. Experimental Design: The peptide a v b 6 -BP was prepared on solid phase and radiolabeled with 4-[ 18 F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired a v b 6 -expressing and a v b 6 -null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired a v b 6 -expressing and a v b 6 -null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer. Results: [ 18 F]a v b 6 -BP displayed excellent affinity and selectivity for the integrin a v b 6 in vitro [IC 50 (a v b 6 ) ¼ 1.2 nmol/L vs IC 50 (a v b 3 ) >10 mmol/L] in addition to rapid target-specific cell binding and internalization (72.5% 0.9% binding and 52.5% 1.8%, respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [ 18 F]a v b 6 -BP was rapid, primarily via the kidneys. In patients, [ 18 F]a v b 6 -BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [ 18 F]a v b 6 -BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung. Conclusions: The clinical impact of [ 18 F]a v b 6 -BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.
UR - http://www.scopus.com/inward/record.url?scp=85061593548&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061593548&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-18-2665
DO - 10.1158/1078-0432.CCR-18-2665
M3 - Article
C2 - 30401687
AN - SCOPUS:85061593548
VL - 25
SP - 1206
EP - 1215
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 4
ER -