TY - JOUR
T1 - Assessment of cellular proliferation in tumors by PET using 18F-ISO-1
AU - Dehdashti, Farrokh
AU - Laforest, Richard
AU - Gao, Feng
AU - Shoghi, Kooresh I.
AU - Aft, Rebecca L.
AU - Nussenbaum, Brian
AU - Kreisel, Friederike H.
AU - Bartlett, Nancy L.
AU - Cashen, Amanda
AU - Wagner-Johnson, Nina
AU - MacH, Robert H.
PY - 2013/3/1
Y1 - 2013/3/1
N2 - This first study in humans was designed to evaluate the safety and dosimetry of a cellular proliferative marker, N-(4-(6,7- dimethoxy-3,4- dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)- 5-methylbenzamide (18F-ISO-1), and evaluate the feasibility of imaging tumor proliferation by PET in patients with newly diagnosed malignant neoplasms. Methods: Patients with biopsy-proven lymphoma, breast cancer, or head and neck cancer underwent 18F-ISO-1 PET. Tumor 18F-ISO-1 uptake was assessed semiquantitatively by maximum standardized uptake value, ratios of tumor to normal tissue and tumor to muscle, and relative distribution volume ratio. The PET results were correlated with tumor Ki-67 and mitotic index, from in vitro assays of the tumor tissue. The biodistribution of 18F-ISO-1 and human dosimetry were evaluated. Results: Thirty patients with primary breast cancer (n = 13), head and neck cancer (n = 10), and lymphoma (n = 7) were evaluated. In the entire group, tumor maximum standardized uptake value and tumor-to-muscle ratio correlated significantly with Ki-67 (τ = 0.27, P = 0.04, and τ = 0.38, P = 0.003, respectively), but no significant correlation was observed between Ki-67 and tumor-to-normal-tissue ratio (τ = 0.07, P = 0.56) or distribution volume ratio (τ = 0.26, P = 0.14). On the basis of whole-body PET data, the gallbladder is the dose-limiting organ, with an average radiation dose of 0.091 mGy/MBq. The whole-body and effective doses were 0.012 mGy/MBq and 0.016 mSv/MBq, respectively. No adverse effects of 18F-ISO-1 were encountered. Conclusion: The presence of a significant correlation between 18F-ISO-1 and Ki-67 makes this agent promising for evaluation of the proliferative status of solid tumors. The relatively small absorbed doses to normal organs allow for the safe administration of up to 550 MBq, which is sufficient for PET imaging in clinical trials. COPYRIGHT
AB - This first study in humans was designed to evaluate the safety and dosimetry of a cellular proliferative marker, N-(4-(6,7- dimethoxy-3,4- dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)- 5-methylbenzamide (18F-ISO-1), and evaluate the feasibility of imaging tumor proliferation by PET in patients with newly diagnosed malignant neoplasms. Methods: Patients with biopsy-proven lymphoma, breast cancer, or head and neck cancer underwent 18F-ISO-1 PET. Tumor 18F-ISO-1 uptake was assessed semiquantitatively by maximum standardized uptake value, ratios of tumor to normal tissue and tumor to muscle, and relative distribution volume ratio. The PET results were correlated with tumor Ki-67 and mitotic index, from in vitro assays of the tumor tissue. The biodistribution of 18F-ISO-1 and human dosimetry were evaluated. Results: Thirty patients with primary breast cancer (n = 13), head and neck cancer (n = 10), and lymphoma (n = 7) were evaluated. In the entire group, tumor maximum standardized uptake value and tumor-to-muscle ratio correlated significantly with Ki-67 (τ = 0.27, P = 0.04, and τ = 0.38, P = 0.003, respectively), but no significant correlation was observed between Ki-67 and tumor-to-normal-tissue ratio (τ = 0.07, P = 0.56) or distribution volume ratio (τ = 0.26, P = 0.14). On the basis of whole-body PET data, the gallbladder is the dose-limiting organ, with an average radiation dose of 0.091 mGy/MBq. The whole-body and effective doses were 0.012 mGy/MBq and 0.016 mSv/MBq, respectively. No adverse effects of 18F-ISO-1 were encountered. Conclusion: The presence of a significant correlation between 18F-ISO-1 and Ki-67 makes this agent promising for evaluation of the proliferative status of solid tumors. The relatively small absorbed doses to normal organs allow for the safe administration of up to 550 MBq, which is sufficient for PET imaging in clinical trials. COPYRIGHT
KW - Cancer
KW - Cell proliferation
KW - F-ISO-1
KW - PET
UR - http://www.scopus.com/inward/record.url?scp=84874882616&partnerID=8YFLogxK
U2 - 10.2967/jnumed.112.111948
DO - 10.2967/jnumed.112.111948
M3 - Article
C2 - 23359657
AN - SCOPUS:84874882616
SN - 0161-5505
VL - 54
SP - 350
EP - 357
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 3
ER -