⁶⁴Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors

⁶⁴Cu (half-life, 12.7 h; β⁺, 0.653 MeV [17.4%]; β^-, 0.579 MeV [39%]) has shown potential as a radioisotope for PET imaging and radiotherapy. ¹¹¹ln-diethylenetriaminepentaacetic acid (DTPA)-D-Phe¹-octreotide (OC) was developed for imaging somatostatin-receptor-positive tumors using conventional scintigraphy. With the advantages of PET over conventional scintigraphy, an agent for PET imaging of these tumors is desirable. Here, we show that ⁶⁴Cu-TETA-OC (where TETA is 1,4,8,11-tetraazacyclotetradecane-N,N′,N″,N‴-tetraacetic acid) and PET can be used to detect somatostatin-receptor-positive tumors in humans. Methods: Eight patients with a history of neuroendocrine tumors (five patients with carcinoid tumors and three patients with islet cell tumors) were imaged by conventional scintigraphy with ¹¹¹In-DTPA-OC (204-233 MBq [5.5- 6.3 mCi]) and by PET imaging with ⁶⁴Cu-TETA-OC (111 MBq [3 mCi]). Blood and urine samples were collected for pharmacokinetic analysis. PET images were collected at times ranging from 0 to 36 h after injection, and the absorbed doses to normal organs were determined. Results: In six of the eight patients, cancerous lesions were visible by both ¹¹¹In-DTPA-OC SPECT and ⁶⁴Cu-TETA-OC PET. In one patient, ¹¹¹In-DTPA-OC showed mild uptake in a lung lesion that was not detected by ⁶⁴Cu-TETA-OC PET. In one patient, no tumors were detected by either agent; however, pathologic follow-up indicated that the patient had no tumors. In two patients whose tumors were visualized with ¹¹¹In-DTPA-OC and ⁶⁴Cu-TETA-OC, ⁶⁴Cu-TETA-OC and PET showed more lesions than ¹¹¹In-DTPA-OC. Pharmacokinetic studies showed that ⁶⁴Cu-TETA-OC was rapidly cleared from the blood and that 59.2% ± 17.6% of the injected dose was excreted in the urine. Absorbed dose measurements indicated that the bladder wall was the dose-limiting organ. Conclusion: The high rate of lesion detection, sensitivity, and favorable dosimetry and pharmacokinetics of ⁶⁴Cu-TETA-OC indicate that it is a promising radiopharmaceutical for PET imaging of patients with neuroendocrine tumors.