TY - JOUR
T1 - Clinical PET of neuroendocrine tumors using 64Cu-DOTATATE
T2 - first-in-humans study
AU - Pfeifer, Andreas Klaus
AU - Knigge, Ulrich
AU - Mortensen, Jann
AU - Oturai, Peter
AU - Berthelsen, Anne Kiil
AU - Loft, Annika
AU - Binderup, Tina
AU - Rasmussen, Palle
AU - Elema, Dennis Ringkjøbing
AU - Klausen, Thomas Levin
AU - Holm, Søren
AU - von Benzon, Eric
AU - Højgaard, Liselotte
AU - Kjaer, Andreas
PY - 2012/8/1
Y1 - 2012/8/1
N2 - The use of positron emitter-labeled compounds for somatostatin receptor imaging (SRI) has become attractive because of the prospect of improved spatial resolution, accelerated imaging procedures, and the ability to quantify tissue radioactivity concentrations. This paper provides results from first-in-humans use of 64Cu-DOTATATE, an avidly binding somatostatin receptor ligand linked to a radioisotope with intermediate half-life and favorable positron energy (half-life, 12.7 h; maximum positron energy, 0.653 MeV). Methods: In a prospective setup, 14 patients with a history of neuroendocrine tumors underwent both PET/CT with 64Cu-DOTATATE and SPECT/CT with our current routine imaging agent 111In-diethylenetriaminepentaacetic acid-octreotide. After intravenous injection of 193-232 MBq of 64Cu-DOTATATE, whole-body PET scans were acquired at 1 h (n = 14), 3 h (n = 12), and 24 h (n = 5) after administration. Tissue radioactivity concentrations for normal organs and lesions were quantified, and standardized uptake values were calculated for the early (1 h) and delayed (3 h) scans. Using the data for 5 patients, we assessed the radiation dose with OLINDA/EXM software. Furthermore, the clinical performance of 64Cu-DOTATATE with respect to lesion detection was compared with conventional SRI. Results: SRI with 64Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3 h. Compared with conventional scintigraphy, 64Cu-DOTATATE PET identified additional lesions in 6 of 14 patients (43%). In 5 patients, lesions were localized in organs and organ systems not previously known as metastatic sites, including the early-stage detection of a secondary neuroendocrine tumor in a patient with a known mutation in the multiple endocrine neoplasia type I gene. All major additional findings seen only on PET could be confirmed on the basis of a clinical follow-up interval of 18 mo. Calculated radiation dose estimates yielded an effective dose of 6.3 mSv for an injected activity of 200 MBq of 64Cu-DOTATATE, with the liver being the organ with the highest absorbed radiation dose (0.16 mGy/MBq). Conclusion: This first-in-humans study supports the clinical use of 64Cu-DOTATATE for SRI with excellent imaging quality, reduced radiation burden, and increased lesion detection rate when compared with 111In-diethylenetriaminepentaacetic acid-octreotide.
AB - The use of positron emitter-labeled compounds for somatostatin receptor imaging (SRI) has become attractive because of the prospect of improved spatial resolution, accelerated imaging procedures, and the ability to quantify tissue radioactivity concentrations. This paper provides results from first-in-humans use of 64Cu-DOTATATE, an avidly binding somatostatin receptor ligand linked to a radioisotope with intermediate half-life and favorable positron energy (half-life, 12.7 h; maximum positron energy, 0.653 MeV). Methods: In a prospective setup, 14 patients with a history of neuroendocrine tumors underwent both PET/CT with 64Cu-DOTATATE and SPECT/CT with our current routine imaging agent 111In-diethylenetriaminepentaacetic acid-octreotide. After intravenous injection of 193-232 MBq of 64Cu-DOTATATE, whole-body PET scans were acquired at 1 h (n = 14), 3 h (n = 12), and 24 h (n = 5) after administration. Tissue radioactivity concentrations for normal organs and lesions were quantified, and standardized uptake values were calculated for the early (1 h) and delayed (3 h) scans. Using the data for 5 patients, we assessed the radiation dose with OLINDA/EXM software. Furthermore, the clinical performance of 64Cu-DOTATATE with respect to lesion detection was compared with conventional SRI. Results: SRI with 64Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3 h. Compared with conventional scintigraphy, 64Cu-DOTATATE PET identified additional lesions in 6 of 14 patients (43%). In 5 patients, lesions were localized in organs and organ systems not previously known as metastatic sites, including the early-stage detection of a secondary neuroendocrine tumor in a patient with a known mutation in the multiple endocrine neoplasia type I gene. All major additional findings seen only on PET could be confirmed on the basis of a clinical follow-up interval of 18 mo. Calculated radiation dose estimates yielded an effective dose of 6.3 mSv for an injected activity of 200 MBq of 64Cu-DOTATATE, with the liver being the organ with the highest absorbed radiation dose (0.16 mGy/MBq). Conclusion: This first-in-humans study supports the clinical use of 64Cu-DOTATATE for SRI with excellent imaging quality, reduced radiation burden, and increased lesion detection rate when compared with 111In-diethylenetriaminepentaacetic acid-octreotide.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Neuroendocrine Tumors
KW - Octreotide
KW - Organometallic Compounds
KW - Positron-Emission Tomography
KW - Quality Control
KW - Radiation Dosage
KW - Radiochemistry
KW - Tomography, Emission-Computed, Single-Photon
U2 - 10.2967/jnumed.111.101469
DO - 10.2967/jnumed.111.101469
M3 - Journal article
C2 - 22782315
SN - 0161-5505
VL - 53
SP - 1207
EP - 1215
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 8
ER -