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Neotect

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NeoTect

CLINICAL PHARMACOLOGY

General

Technetium Tc 99m Depreotide Injection is a diagnostic radiopharmaceutical based upon a synthetic peptide with high affinity binding to somatostatin receptors (SSTR) in normal and abnormal tissues. (See Pharmacodynamics section for details).

Pharmacokinetics

Technetium Tc 99m radioactivity pharmacokinetic parameters were evaluated after a single intravenous administration of Depreotide containing 15-20 mCi of Technetium Tc 99m and 47 g of Depreotide in normal subjects and in patients with selected disorders. The pharmacokinetic values were estimated from data corrected for radioactivity decay. The total radioactivity in the blood exhibited three-exponential phases with the pharmacokinetic parameters shown in Table 4.

Table 4. Pharmacokinetics Parameters of Technetium Tc 99m Depreotide Radioactivity (a)

Subjects Effective Half-Life Vss CL total CL renal
ta (min) tβ (min) tγ (hour) (L/kg) (mL/min/kg) (mL/min/kg)
Normal
(n=9)
4.3 2.5 43.6 11.5 22.4 11.90 1.56 0.85 2.12 1.3 0.37 0.22
Hepatic dysfunction
(n=3)
4.0 0.4 48.3 7.5 18.0 3.3 1.7 0.4 2.45 0.3 0.24 (n=1)
Renal dysfunction
(n=3)
2.9 0.7 52.0 9.9 17.2 8.2 1.49 0.95 1.49 0.72 Not evaluated
Lung cancer
(n=2) (b)
4.5, 9.1 62, 72 12.6, 16.9 0.44, 1.43 1.64, 1.64 Not evaluated
(a) Only radioactivity was measured. Data expressed as mean value ± SD (n) where "n" is the number of subjects or patients.
(b) Only two lung cancer patients were studied; the calculated values for both patients are presented.

The pharmacokinetics of Depreotide peptide without the Technetium Tc 99m have not been studied.

Protein Binding

In vivo plasma protein binding of total radioactivity (5-min plasma sample) was determined by the centrifuge assisted ultrafiltration method. Mean protein binding of Depreotide total radioactivity ranged from 11-21% (Table 5).

External whole-body gamma scintigraphy showed highest localization of radioactivity in liver and kidney.

Table 5. Plasma protein binding data.*

Subjects Protein binding % bound
Normal 11.4 2.10 (n=11)
Hepatic dysfunction 11.4 1.89 (n=5)
Renal dysfunction 11.7 2.05 (n=4)
Lung cancer 20.7 (n=1)
*Data expressed as mean value SD

Metabolism

The metabolism and disposition of Depreotide peptide without the Technetium Tc 99m have not been studied in humans. Preliminary data from the elimination of radioactivity show that in patients and healthy volunteers at four hours after a single intravenous dose of depreotide (containing 15-20 mCi of Technetium Tc 99m and 47g of depreotide), 71-84% of the Technetium Tc 99m in blood and 61-64% of the Technetium Tc 99m in urine are bound to depreotide. The fate of the remaining percentages has not been evaluated.

Elimination

In healthy subjects, 12% of the radioactivity is eliminated by renal clearance, the majority of which occurs by 4 hours. The elimination of the remaining 88% radioactivity has not been studied.

Special Populations

The pharmacokinetics of the Technetium Tc 99m Depreotide Injection have not been determined in geriatric, pediatric, renally impaired and hepatically impaired patients.

Gender Effect: In a study of 17 subjects (10 men and 7 women) as shown in Table 6, women appeared to have less total clearance of radioactivity.

Table 6. Gender Differences in Pharmacokinetics Parameters of Technetium Tc 99m Depreotide Radioactivity*

Parameter Male (n=10) Female (n=7)
CL total (mL/min/kg)* 2.3 1.1 1.6 0.75
Vss (L/kg) 1.50 0.65 1.49 0.95
T½ a (min) 4.2 1.8 4.4 2.9
T½ β (min) 52.1 10.1 44 14.0
T½ γ (hour) 18.3 7.8 21.9 10.5
*Data expressed as mean value SD

Drug - Drug Interactions

Formal in vivo and in vitro drug-drug interaction studies have not been conducted.

Pharmacodynamics

In animal models and in vitro human cell lines, depreotide peptide without the Technetium Tc 99m was shown to bind to somatostatin receptors (SSTR) that predominantly are subtype 2, 3 and 5. SSTR 3 is a vasoactive intestinal peptide (VIP) receptor site. The possibility of VIP stimulating activity has not been studied.

Results of glucose tolerance tests in 9 healthy volunteers were normal after administration of depreotide peptide without the Technetium Tc 99m.

Clinical Studies

A total of 270 patients with known cancer or a high suspicion of cancer of the lung was studied in two multi-center, open administration, blind image interpretation clinical studies of Technetium Tc 99m Depreotide Injection. Of these patients, there were 168 (62%) men and 102 (38%) women with a mean age of 65 years (range: 29 to 86 years). Patients with known active pulmonary infections were excluded.

Eligible patients had either a known diagnosis of or were highly suspect for cancer, had a lung lesion on computed tomography (CT) scan or chest x-ray, and were scheduled for biopsy of the lesion. All patients had scintigraphic imaging with NeoTect® (technetium tc 99m depreotide injection) at a dose of 444 to 1221 MBq (12 to 33 mCi); and 18-47g of peptide. The NeoTect® (technetium tc 99m depreotide injection) images were scored as positive for malignancy if there was any uptake in the right or left lung, mediastinum or hilar region that was not characteristic of general radiopharmaceutical regional uptake. The NeoTect® (technetium tc 99m depreotide injection) images were scored negative if abnormal localization was not found. The criteria for the interpretation of malignancy by CT were similarly based upon abnormal visualization.

The NeoTect® (technetium tc 99m depreotide injection) and CT scans were interpreted blindly by three nuclear medicine physicians and three radiologists, respectively. The majority score for the presence or absence of malignancy was used in the statistical analysis. The location and score of NeoTect® (technetium tc 99m depreotide injection) and CT scan results were compared with the biopsy results of the presenting lesion identified at study enrollment. The results were analyzed for sensitivity, specificity, and accuracy (percentage of correct diagnoses). These results are presented in table 7.

Table 7: NeoTect® (technetium tc 99m depreotide injection) Blinded SPECT Imaging Results (a) for the Main Presenting Lesion Comparison to Histopathology

  Sensitivity Specificity Accuracy
Study A (n=112)(b) 70% [60, 80] 86% [73, 99] 74% [66, 81]
Study B (n = 114)(b) 71% [62, 80] 79% [58, 100] 72% [64, 79]
(a) As percentage [confidence intervals]
(b) Total of 226 patients were evaluated. Sixteen patients in Study A and 28 patients in study B were not evaluated primarily because of missing biopsies.

The prevalence of malignancy in the evaluated 226 patients was high (75% in study A; 88% in study B). In these 226 patients, the lesions that were biopsy positive for malignancy had histopathology results consistent with squamous cell (34%), adenocarcinoma (32%), other non-small cell (21%), small cell (6%), and other malignant cell types (7%).

The interpretation of NeoTect® (technetium tc 99m depreotide injection) images was negative in 29% (54/184) of patients when the biopsy reports were positive for adenocarcinoma, squamous cell, carcinoid or non-small cell cancer (i.e., false-negative NeoTect® (technetium tc 99m depreotide injection) scans). In these patients the lesion size ranged from 1-7 cm on CT. Also, the interpretation of NeoTect® (technetium tc 99m depreotide injection) was positive in 17% (7/42) of patients when the biopsy results were consistent with acute or chronic inflammation, infectious processes including abscess and pneumonia, hamartoma, fibrosis, or caseating or non-caseating granulomas (i.e., false-positive NeoTect® (technetium tc 99m depreotide injection) scans).

In these two studies of patients who were suspect for malignancy, two different retrospective analyses were performed to explore the potential diagnostic use of combined NeoTect® (technetium tc 99m depreotide injection) and CT blinded- image interpretations. One retrospective analysis of a subset of 127 patients with a solitary pulmonary nodule implies the combined interpretation improved specificity. In the other retrospective analysis of all 226 patients who had a CT scan, the finding of a positive CT and a positive NeoTect® (technetium tc 99m depreotide injection) image suggests an improved positive predictive value. The clinical relevance of other combinations of image results (e.g., CT and NeoTect® (technetium tc 99m depreotide injection) both negative, CT negative and NeoTect® (technetium tc 99m depreotide injection) scan positive; or CT positive and NeoTect® (technetium tc 99m depreotide injection) negative) has not been determined. In all patients or in those with a solitary pulmonary nodule, the clinical benefit of combined interpretations has not been studied prospectively.

The clinical benefit of NeoTect® (technetium tc 99m depreotide injection) in other populations of patients (e.g., those who do not have a mass on CT and chest x-ray, and a high clinical suspicion for cancer) has not been studied. The clinical benefit of NeoTect® (technetium tc 99m depreotide injection) as a population-based screening tool has not been studied. NeoTect (technetium tc 99m depreotide injection) ® is not an alternative to CT or biopsy.

Last reviewed on RxList: 12/1/2008
This monograph has been modified to include the generic and brand name in many instances.

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