Source: FDA, National Drug Code (US) Revision Year: 2020
Copper Cu 64 dotatate binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSTR2). It binds to cells that express somatostatin receptors including malignant neuroendocrine cells, which overexpress SSTR2 receptors. Copper Cu 64 is a positron (β+) emitting radionuclide with an emission yield that allows positron emission tomography (PET) imaging.
The relationship between copper Cu 64 dotatate plasma concentrations and successful imaging was not explored in clinical trials.
After 1 to 3 hours of a single dose administration of copper Cu 64 dotatate injection, the maximum radioactivity is observed in adrenal glands, kidney, pituitary glands, spleen, and liver.
The metabolism of copper Cu 64 dotatate is unknown.
Following a single intravenous dose (4.15 ± 0.13 mCi) of Detectnet (n=6), between 16% to 40% radioactivity of the injected dose was recovered in urine over a 6-hour collection time.
The effect of hepatic impairment or renal impairment on copper Cu 64 dotatate pharmacokinetics has not been studied.
Carcinogenicity and mutagenicity studies have not been conducted with copper Cu 64 dotatate injection; however, radiation is a carcinogen and mutagen.
No animal studies were conducted to determine the effects of copper Cu 64 dotatate on fertility or embryology.
The efficacy of Detectnet was established in two single-center, open-label studies. Study 1 prospectively evaluated a total of 63 subjects, including 42 patients with known or suspected NET based on histology, conventional imaging, or clinical evaluations and 21 healthy volunteers. Of the 42 patients, 37 (88%) had a history of NETs at the time of Detectnet imaging. Among the total study population of 63 subjects, 28 (44%) were men and 35 (56%) were women with most subjects being white (86%). The mean age of the subjects was 54 years (range 25 to 82 years).
Detectnet images from each subject were interpreted as either positive or negative for NET by three independent readers who were blinded to clinical information and other imaging results. PET imaging results were compared to a composite reference standard consisting of a single oncologist’s blinded assessment of subject diagnosis based on available histopathology results, reports of conventional imaging (MRI, contrast CT, bone scintigraphy, F 18 fludeoxyglucose PET/CT, F 18 sodium fluoride PET/CT, In 111 pentetreotide SPECT/CT, Ga 68 dotatate PET/CT) performed within 8 weeks prior to Detectnet imaging, and clinical and laboratory data including chromogranin A and serotonin levels. The proportion of subjects positive for disease per composite reference who were identified as positive by Detectnet imaging was used to quantify positive percent agreement. The proportion of subjects without disease per composite reference who were identified as negative by Detectnet imaging was used to quantify negative percent agreement. Table 5 shows the performance of Detectnet in the detection of NET for Study 1.
Table 5. Performance of Detectnet in the detection of NET by reader in Study 1:
| NET status as identified by reader | Reference | ||
|---|---|---|---|
| Positive | Negative | ||
| Reader 1(n=62)* | Positive | 30 | 1 |
| Negative | 3 | 28 | |
| Percent Reader Agreement(95% CI)** | 91 (75, 98) | 97 (80, 99) | |
| Reader 2(n=63) | Positive | 30 | 6 |
| Negative | 3 | 24 | |
| Percent Reader Agreement(95% CI)** | 91 (75, 98) | 80 (61, 92) | |
| Reader 3(n=63) | Positive | 30 | 3 |
| Negative | 3 | 27 | |
| Percent Reader Agreement(95% CI)** | 91 (75, 98) | 90 (72, 97) | |
n: number of patients, CI: confidence interval
* Reader 1 interpreted one of the 63 PET scans as "not evaluable"
** Wilson score interval with continuity correction |
Study 2 showed similar performance through retrospective analysis of published data collected in 112 patients (63 males, 49 females; mean age 62 years, range 30 to 84 years) with a known history of NET.
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