Objective: This study aimed to evaluate whether the presence of high levels of free Sn2+ in pyrophosphate (PYP) kits leads to in vivo red blood cell (RBC) radiolabeling and increased blood pool (BP) radioactivity. Methods: A prospective study was conducted, enrolling 156 patients, including 88 men (56.4%) and 68 women (43.5%) with a mean age of 72.32 ± 12.59 years. The cohort was divided into two groups: the first group (n=78) received 30 mCi of technetium pertechnetate-labeled radiopharmaceutical, while the second group (n=58) received a PYP kit with an additional 90 mCi of radioactivity. Demographic and clinical variables, including age, gender, body mass index (BMI), and creatinine levels, were recorded and analyzed. Univariable and multivariable binary logistic regression analyses were performed to identify factors influencing BP radioactivity. Results: No significant differences in baseline characteristics were observed between the groups (P > 0.05). Univariable binary logistic regression analysis indicated that gender, age, and BMI did not significantly affect BP radioactivity (P > 0.05). However, creatinine levels and the amount of added radioactivity to the PYP kit were significant factors influencing BP radioactivity (P < 0.05). Multivariable logistic regression confirmed that creatinine levels (P < 0.001) and increased radioactivity (P = 0.005) significantly contributed to BP activity visualization. Further stratification based on creatinine levels showed no significant difference in BP activity among patients with creatinine>1.5 mg/dL (P = 0.350). In contrast, a significant difference was observed in patients with creatinine<1.5 mg/dL (P = 0.021). Conclusion: Our findings suggest that increased free Sn2+ levels in PYP kits contribute to in vivo RBC radiolabeling and elevated BP radioactivity, particularly in patients with normal renal function (creatinine<1.5 mg/dL). These results underscore the need for careful consideration of radioactivity levels in PYP kits to minimize unintended BP activity during imaging.