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Table 1 Clinical studies using *copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) ([*Cu][Cu(ATSM)]) or *Cu-dichloride ([*Cu]CuCl2) as radioactive tracer in PET

From: Hypoxia imaging and theranostic potential of [64Cu][Cu(ATSM)] and ionic Cu(II) salts: a review of current evidence and discussion of the retention mechanisms

TracerTumor typePatient No.Results/ConclusionsReference
[*Cu][Cu(ATSM)]Lung cancer662Cu-ATSM rapidly accumulated in tumors of patients with lung cancer but not in the lung of healthy volunteers. The level of radiocopper reached abnormally intense plateau levels within a few minutes after intravenous administration in tumors with different distribution from [18F]-FDG.[39]
Lung cancer (NSCLC)19PET imaging with 60Cu-ATSM in patients with NCSLC is feasible. At a tumor (T)/muscle (M) threshold of 3.0 clear distinct prediction can be made between patients that respond to therapy (mean T/M = 1.5 ± 0.4) and the non-responders (mean T/M = 3.4 ± 0.8). No significant difference in tumor SUV was observed with [18F]-FDG.[31]
Cervical cancer14Tumor uptake of 60Cu-ATSM inversely correlate with progression-free and overall survival. Uptake of [18F]-FDG did not correlate with 60Cu-ATSM and no significant [18F]-FDG distribution difference between hypoxic and normoxic tumors.[40]
Cervical cancer15Patients with hypoxic cancer as determined by 60Cu-ATSM correlates with overexpressed VEGF, EGFR, COX-2, CA-9, as well as high apoptotic and worse prognosis.[110]
Cervical cancer38Patients were monitored through a period from 3 to 79 months. With a threshold of T/M = 3.5 the 3-year progression free and cause-specific survival rate of patients with normoxic tumors (T/M < 3.5, 71%) is significantly higher than that of hypoxic tumor (T/M > 3.5, 28%). Advantages of 60Cu-ATSM over 18F-FMISO include much faster pharmacokinetics which results in better target-to-background ratio, and no interference due to urinary bladder uptake.[32]
Rectal1960Cu-ATSM PET may be predictive of survival and possible tumor response to neoadjuvant chemoradiotherapy in rectal cancer.[34]
Cervical cancer10PET images from [64Cu][Cu(ATSM)] have better image quality (lower noise) than images from [60Cu][Cu(ATSM)]. Patterns and magnitude of the tumors were similar between the two tracers with different copper isotopes.[111]
Lung cancer13SUV of 62Cu-ATSM is higher than [18F]-FDG at the peripheral region of tumor while [18F]-FDG is higher at the center of the tumor. This difference of intratumor distribution indicates the difference of high glucose metabolism regions and hypoxia region inside various histopathologic types of lung cancer.[41]
Head and neck17Increased uptake of [62Cu][Cu(ATSM)] predicted tumor resistance to chemo- and radiotherapy as well as recurrence.[35]
Head and neck30Among 27 patients with squamous cell carcinoma, [62Cu][Cu(ATSM)] showed higher accumulation in the peripheral regions than in the center of the tumor mass, opposite to the accumulation pattern of [18F]-FDG. In 3 patients with adenocarcinoma, the accumulation of both 62Cu-ATSM and [18F]-FDG were homogeneous.[33]
Glioma22Uptake (SUVmax) and T/B ratio of [62Cu][Cu(ATSM)] were much higher in grade IV than grade III/II gliomas, correlated with MRI findings of necrosis. At T/B=1.8 threshold, [62Cu][Cu(ATSM)] is predictive of HIF-1a expression, with 92.3% sensitivity and 88.9% specificity.[112]
Head and neck25At T/M = 3.2 [62Cu][Cu(ATSM)] uptake threshold, patients with hypoxic tumors have significant worse 2-year progression free survival (20%) and cause-specific survival (33%), compares to patients with lower [62Cu][Cu(ATSM)] uptake (73% and 80%, respectively).[113]
Head and neck11[64Cu][Cu(ATSM)] has very high sensitivity (100%) of predicting radiotherapy response, but relatively low specificity for the prediction of neoadjuvant chemoradiotherapy response.[114]
Head and neck30With a cut-off TMR of 3.2, patients with hypoxic tumors have significantly worse progression-free survival and cause-specific survival. 62Cu-ATSM is predictive of treatment resistance and poor prognosis for head and neck cancers.[115]
Lung /H&N7/11Moderate to high uptake of [64Cu][Cu(ATSM)] were found in all patients. No statistic significant difference in SUV between the two tumor types.[116]
Ionic copper (II)Prostate cancer7Due to the absence of urinary excretion lesions in the pelvic area can be easily imaged with [64Cu]CuCl2-PET. No adverse or clinical detectable pharmacologic effects were observed in any of the patients at mean activity of 339 MBq (4 MBq/kg).[36]
Brain cancer19Using [64Cu]CuCl2 the brain cancerous lesions can be clearly visualized at 1 h after the injection and have stable retention between 3-24 hours. Accumulation of the tracer in consistent agreement with MRI images. The brain lesions were also clearly visualized in patients simultaneously affected by other types of cancer.[38]
Healthy volunteer6Healthy volunteers were injected with [64Cu]CuCl2 at a dose of 4.0 MBq/kg. No observable adverse effects, clinically detectable pharmacologic effects, and change in standard vital signs were observed. Uptake of copper-64 was observed predominantly in liver, followed by bowel and kidneys.[101]
Prostate cancer50Among the 50 patients, 41 were detected (82%) positive via [64Cu]Cu-PET, compared to 56% using [18F]F-choline PET and 74% using multiparametric MRI. Unlike [18F]F-choline, [64Cu]CuCl2 allows thorough pelvic exploration due to lack of excreted or accumulated urinary tract.[37]
Prostate cancer50The maximum tumor-to-background ratio was reached 1 hour after injection. Mean SUVmax in lymph nodes and bone metastases were significantly higher than local relapse. Discounting the Auger electrons, the mean absorbed dose for PCa lesions per administration was ~0.06 mGy/MBq. The therapeutic effect of [64Cu]CuCl2 is mainly dependent on the Auger electron emission instead of beta radiation.[58]
  1. * Atomic mass number