FIGURE 1.

MIP images of serial ⁶⁸Ga-DOTATATE PET studies of a woman with biopsy-proven metastatic well-differentiated neuroendocrine tumor (WHO grade 1). Initial time point (A) demonstrates ⁶⁸Ga-DOTATATE–avid retroperitoneal nodal disease (green circle) and typical low blood pool activity (red arrows). Follow-up ⁶⁸Ga-DOTATATE PET (B) after commencement of lanreotide therapy demonstrates interval increased blood pool uptake (red arrows) and interval decreased uptake in the liver, spleen, and retroperitoneal lymph nodes (green circle). Subsequent ⁶⁸Ga-DOTATATE PET (C) demonstrated interval resolution of blood pool uptake (red arrows) and increased ⁶⁸Ga-DOTATATE uptake in retroperitoneal lymph nodes (green circle). As seen here, physiologic biodistribution of ⁶⁸Ga-DOTATATE includes the pituitary and salivary glands, liver, spleen, kidney, adrenals, pancreas, and some gastrointestinal and marrow uptake.^1,2 Increased blood pool component has been described for ⁶⁷Ga-citrate but not for ⁶⁸Ga-DOTATATE,³ and ⁶⁸Ga-DOTATATE has been shown to have high in vitro and in vivo stability at many time points.^4,5 However, informal communications with the manufacturer and unpublished work from our radiochemistry department have confirmed that ⁶⁸Ga can have suboptimal binding to the DOTA cage and may bind to blood products such as transferrin.⁶ The high blood pool ⁶⁸Ga uptake in this patient is believed to be unbound ⁶⁸Ga, as DOTA conjugated ⁶⁸Ga clears rapidly from the blood.⁷ The probability of unbound ⁶⁸Ga is most likely independent of the production of ⁶⁸Ga, whether via generator or cyclotron.^8,9 Preclinical studies demonstrates that ¹⁷⁷Lu-DOTATATE has similar binding stability to ⁶⁸Ga-DOTATATE,¹⁰ and thus although rare, incomplete binding of ¹⁷⁷Lu-DOTATATE could in theory result in suboptimal treatments.