PT - JOURNAL ARTICLE AU - Farrokh Dehdashti AU - Richard Laforest AU - Feng Gao AU - Kooresh I. Shoghi AU - Rebecca L. Aft AU - Brian Nussenbaum AU - Friederike H. Kreisel AU - Nancy L. Bartlett AU - Amanda Cashen AU - Nina Wagner-Johnson AU - Robert H. Mach TI - Assessment of Cellular Proliferation in Tumors by PET Using <sup>18</sup>F-ISO-1 AID - 10.2967/jnumed.112.111948 DP - 2013 Mar 01 TA - Journal of Nuclear Medicine PG - 350--357 VI - 54 IP - 3 4099 - http://jnm.snmjournals.org/content/54/3/350.short 4100 - http://jnm.snmjournals.org/content/54/3/350.full SO - J Nucl Med2013 Mar 01; 54 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.