TY - JOUR T1 - Effects of 68Ga-DOTATOC specific activity on somatostatin receptor quantitation JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 360 LP - 360 VL - 57 IS - supplement 2 AU - Pedram Heidari AU - Francis Deng AU - Shadi Esfahani AU - Benjamin Larimer AU - Umar Mahmood Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/360.abstract N2 - 360Objectives Stringent specific activity (SA) control is part of the quality assessment for functional receptor imaging studies using PET. However, only scarce data is available on the impact of the SA in cancer receptor imaging. This study evaluates the effect of SA on 68Ga-DOTATOC uptake in somatostatin receptor (SSTR) expressing tumor models.Methods In-vitro, SSTR2 expression level was assessed using Western blot across multiple cancer lines including IMR32, Capan1, A549 and AR42J, and was normalized to β-actin expression. The SSTR2/β-actin ratio was correlated to in-vitro 68Ga-DOTATOC uptake and normalized to cell counts. AR42J and IMR32 normalized 68Ga-DOTATOC uptake was plotted against 68Ga-DOTATOC SA ranging from 0.2 to 20 Ci/g and correlation was assessed. Competitive binding assay using high (120 Ci/g) and low SA (60 Ci/g) 68Ga-DOTATOC with different doses of octreotide was performed in AR42J cells. For in-vivo studies Institutional Animal Care and Use Committees approval was obtained. Subcutaneous AR42J xenografts were implanted in Nu/Nu mice. Dynamic PET scans in list mode were acquired following injection of 68Ga-DOTATOC with a wide range of SAs (0.3 - 50 Ci/g). Net tracer influx (Ki), SUVmax and SUVmean were plotted against the SA to established the correlation between quantitative parameters and SA. Patlak-plot was used to calculate the tracer influx constant for the tumor ((Ki= (k1 × k3 / k2 + k3)). Moreover, AR42J xenografts were imaged before and after treatment with IV octreotide using high and low SA 68Ga-DOTATOC and differences in Ki and SUVmean were analyzed.Results We observed a linear relation between 68Ga-DOTATOC uptake per cell and normalized SSTR2 expression across the cell lines (R2=0.95, p<0.024). We demonstrated a linear correlation between the SA and 68Ga-DOTATOC uptake per cell in IMR32 (R2=0.98, P<0.015) and AR42J (R2=0.99, P<0.005). Competitive octreotide displacement curves showed an essentially equal IC50 of the in low SA and high SA groups, but 35% lower Bmax in the Low SA compared to high SA group. We found that Ki, SUVmax, and SUVmean decreased in a linear fashion with reduction in SA. Quantitative 68Ga-DOTATOC PET parameters had a direct linear correlation with the SA (R2=0.89, p<0001 for Ki, R2=0.66, p<0.0001 for SUVmax and R2=0.82 and p<0.0001 for SUVmean). With octreotide treatment both low and high SA groups showed lower SUVmean in after treatment compared to the baseline (p<0.0001), but the uptake values of the high SA group was significantly higher than low SA group at baseline and after therapy (p<0.0001 and p<0.01, respectively).Conclusions 68Ga-DOTATOC uptake is correlated to SSTR2 expression for a given SA. However, 68Ga-DOTATOC uptake in SSTR-expressing tumors increases in a linear fashion with increase in SA. If quantitation for dosimetry and response assessment are considerations, correction for specific activity is warranted. ER -