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

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.

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 50 µg 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.

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.

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.

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^® at a dose of 444 to 1221 MBq (12 to 33 mCi); and 18-50 µg of peptide. The NeoTect^® 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^® 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^® 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^® and CT scan results were compared with the biopsy results of the presenting lesion identified at study enrollment. The results were analyzedfor sensitivity, specificity, and accuracy (percentage of correct diagnoses). These results are presented in table 7.

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^® 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^® scans). In these patients the lesion size ranged from 1-7 cm on CT. Also, the interpretation of NeoTect^® 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^® 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^® 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^® image suggests an improved positive predictive value. The clinical relevance of other combinations of image results (e.g., CT and NeoTect^® both negative, CT negative and NeoTect^® scan positive;or CT positive and NeoTect^® 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^® 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^® as a population-based screening tool has not been studied. NeoTect^® is not an alternative to CT or biopsy.

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