RESUMO
BACKGROUND: In recent years, Copper-64 (T1/2 = 12.7 h) in the chemical form of copper dichloride ([64Cu]CuCl2) has been identified as a potential agent for PET imaging and radionuclide therapy targeting the human copper transporter 1, which is overexpressed in a variety of cancer cells. Limited human biodistribution and radiation dosimetry data is available for this tracer. The aim of this research was to determine the biodistribution and estimate the radiation dosimetry of [64Cu]CuCl2, using whole-body (WB) PET scans in healthy volunteers. Six healthy volunteers were included in this study (3 women and 3 men, mean age ± SD, 54.3 ± 8.6 years; mean weight ± SD, 77.2 ± 12.4 kg). After intravenous injection of the tracer (4.0 MBq/kg), three consecutive WB emission scans were acquired at 5, 30, and 60 min after injection. Additional scans were acquired at 5, 9, and 24 h post-injection. Low-dose CT scan without contrast was used for anatomic localization and attenuation correction. OLINDA/EXM software was used to calculate human radiation doses using the reference adult model. RESULTS: The highest uptake was in the liver, followed by lower and upper large intestine walls, and pancreas, in descending order. Urinary excretion was negligible. The critical organ was liver with a mean absorbed dose of 310 ± 67 µGy/MBq for men and 421 ± 56 µGy/MBq for women, while the mean WB effective doses were 51.2 ± 3.0 and 61.8 ± 5.2 µSv/MBq for men and women, respectively. CONCLUSIONS: To the best of our knowledge, this is the first report on biodistribution and radiation dosimetry of [64Cu]CuCl2 in healthy volunteers. Measured absorbed doses and effective doses are higher than previously reported doses estimated with biodistribution data from patients with prostate cancer, a difference that could be explained not just due to altered biodistribution in cancer patients compared to healthy volunteers but most likely due to the differences in the analysis technique and assumptions in the dose calculation.
RESUMO
OBJECTIVE: To determine the effectiveness of therapy with the radiolabelled somatostatin analogues, 90Y-DOTATOC and 177Lu-DOTATATE, in the treatment of metastatic neuroendocrine tumours with progression to first-line treatment. MATERIAL AND METHODS: A study was conducted on 30 patients diagnosed with neuroendocrine tumours (gastroenteropancreatic, bronchopulmonary, MEN2A, MEN2B, phaeochromocytoma, and paraganglioma) with metastatic disease diagnosed by the pathology department, with progression to first-line treatment, and recruited from December 2014 to February 2016. Efficacy was analysed using computed tomography (CT) according RECIST 1.1 criteria, and the molecular changes using the SUVmax of PET/CT with 68Ga-DOTATOC. Safety was carried out with a renal scan with 99mTc-MAG3. RESULTS: The 30 patients received a total of 49 cycles 90Y-DOTATOC (21 doses) and 177 Lu-DOTATATE (28 doses), with a mean of 1.5 cycles per patient. Of these, 17 (56.7%) showed a partial morphological response, 22 (73.3%) molecular and biochemical response, and 23 (76.6%) clinical response. One patient died during the median follow-up of 13 months. The median overall survival from diagnosis was 54 months (95% CI; 31.18-76.81), and median progression-free survival was 32 months (95% CI; 15.00-48.99). CONCLUSION: Therapy with 90Y-DOTATOC and 177Lu-DOTATATE is a promising therapy for patients with well and moderately differentiated neuroendocrine tumours. The efficacy is better the larger the number of cycles administered, inversely proportional to the number of metastases (<10), and is associated with the level of uptake according to the SUVmax by the metastases, regardless of metabolically active tumour volume.
