64Cu-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors.
64Cu (half-life, 12.7 h; beta+, 0.653 MeV [17.4%]; beta-, 0.579 MeV [39%]) has shown potential as a radioisotope for PET imaging and radiotherapy. (111)In-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 (111)In-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 (111)In-DTPA-OC SPECT and 64Cu-TETA-OC PET. In one patient, (111)In-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 (111)In-DTPA-OC and 64Cu-TETA-OC, 64Cu-TETA-OC and PET showed more lesions than (111)In-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.


CONCLUSIONS
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.
Anderson
C J
CJ
Mallinckrodt Institute of Radiology, Washington University School of Medicine. St. Louis, Missouri 63110, USA.
Dehdashti
F
F
Cutler
P D
PD
Schwarz
S W
SW
Laforest
R
R
Bass
L A
LA
Lewis
J S
JS
McCarthy
D W
DW
D007516:Adenoma, Islet Cell / Q000000981:diagnostic imaging; D000368:Aged; D000818:Animals; D002276:Carcinoid Tumor / Q000000981:diagnostic imaging; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging; D006801:Humans; D007205:Indium Radioisotopes; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000737:chemistry / Q000000981:diagnostic imaging*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging; D010215:Papio; D004369:Pentetic Acid / Q000031:analogs & derivatives*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin / Q000032:analysis; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed
D007205:Indium Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C421169:copper 1,4,8,11--tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid-octreotide; C071632:SDZ 215-811; D004369:Pentetic Acid; D015282:Octreotide