RT Journal Article SR Electronic T1 Assessment of Cellular Proliferation in Tumors by PET Using 18F-ISO-1 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 350 OP 357 DO 10.2967/jnumed.112.111948 VO 54 IS 3 A1 Farrokh Dehdashti A1 Richard Laforest A1 Feng Gao A1 Kooresh I. Shoghi A1 Rebecca L. Aft A1 Brian Nussenbaum A1 Friederike H. Kreisel A1 Nancy L. Bartlett A1 Amanda Cashen A1 Nina Wagner-Johnson A1 Robert H. Mach YR 2013 UL http://jnm.snmjournals.org/content/54/3/350.abstract 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.