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.
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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 -