p-829 and Lung-Neoplasms

Receptors for somatostatin (SST) (SSTR) are expressed on various tumor cells as well as on activated lymphocytes. Previous data have shown that (99m)Tc-P829 binds with high affinity to many different types of tumor cells as well as to leukocytes via the human hSSTR2, hSSTR3, and hSSTR5 target receptors. Consequently, (99m)Tc-P829 was successfully introduced as a peptide tracer for tumor imaging. In this study, we evaluated the orbital uptake of (99m)Tc-P829 in patients with active and inactive thyroid-associated orbitopathy (TAO), accompanied by lymphocyte infiltration in the acute stage and by muscle fibrosis in the chronic stage of the disease.. To evaluate its clinical usefulness in Graves' disease, (99m)Tc-P829 scintigraphy (approximately equal to 740 MBq) was performed in 44 patients with TAO (median duration, 19 mo; range, 1-360 mo). The clinical activity of the orbital disease was graded by the NOSPECS (no signs or symptoms; only signs, no symptoms; signs only; proptosis; eye muscle involvement; corneal involvement; sight visual acuity reduction) classification of the American Thyroid Association, the clinical activity score (CAS), and the superonasal index (SNI). SPECT (360 degrees ) and planar studies were completed within 3 h after injection. Orbital (O) regions of interest (ROIs) were compared with temporoparietal and occipital (OCC) ROIs. Orbital uptake ratios in Graves' disease were compared with data obtained from lung cancer patients with no eye disease (n = 22).. Overall, (99m)Tc-P829 biokinetics were the same in Graves' disease patients as in lung cancer patients, showing a rapid blood clearance and visualization of the facial bones within minutes of injection. In all control patients, the orbit appeared as a "cold area," whereas visual orbital accumulation of (99m)Tc-P829 was found in patients with active TAO (O/OCC ratios: 1.26 +/- 0.04 vs. 1.69 +/- 0.04; P < 0.01, respectively). Patients with active eye disease (n = 25) presented with an increased orbital uptake of (99m)Tc-P829 compared with patients with inactive disease (n = 19; O/OCC ratio: 1.12 +/- 0.05; P < 0.01). A statistically significant correlation was found between CAS and the orbital uptake (O/OCC ratio) values (r = 0.90), whereas no correlation could be documented regarding the NOSPECS classification as well as the SNI.. In TAO, (99m)Tc-P829 yields high orbital binding with good clinical correlation. The better image quality due to the high energy of technetium, the lower radiation dose for patients and personnel, and the short acquisition protocol favor SSTR scintigraphy with (99m)Tc-P829 over (111)In-labeled compounds. The in-house availability of the radiotracer and cost-effectiveness are further advantages.

Topics: Cornea; Female; Graves Disease; Humans; Lung Neoplasms; Male; Middle Aged; Oculomotor Muscles; Orbit; Organotechnetium Compounds; Peptides, Cyclic; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Statistics as Topic; Tissue Distribution

Many neoplasms including small cell cancers more densely express somatostatin-type receptors or more avidly bind somatostatin than granulomatous and other nonmalignant processes. While non-small cell neoplasms of the lung have not yet been shown to demonstrate this receptor expression, previous studies have documented non-small cell lung cancer detection with somatostatin analog scintigraphy. This phenomenon can be conceivably exploited utilizing technetium Tc-99m P829 (P829), a unique low molecular weight somatostatin-type receptor binding polypeptide radiopharmaceutical. The objective of this study was to determine the ability of P829 scintigraphy to noninvasively differentiate malignant and nonmalignant solitary pulmonary nodules (SPNs).. The radiopharmaceutical technetium 99mTc-P829 was utilized for scintigraphy including single photon emission computed tomography. Thirty individuals with indeterminate SPNs of > or = 1 cm and significant risk factors for primary lung cancer were identified and underwent P829 scintigraphy. Tissue diagnosis was then established by transthoracic needle biopsy specimens.. Fourteen subjects demonstrated abnormal P829 scans in the region of the radiographic abnormality. Twelve of this group had biopsy specimens revealing neoplasia. Two subjects with necrotizing granuloma on biopsy specimen had abnormal P829 scans in the region of the nodule. Sixteen subjects had no abnormal P829 tracer uptake in the region of the nodule. Fourteen subjects had benign diagnoses on biopsy specimens. One member of this group with a non-diagnostic biopsy specimen refused thoracotomy and remains radiographically stable at 24 months of follow-up. One subject with a squamous cell carcinoma demonstrated no P829 activity in the region of the nodule. The specificity of P829 scintigraphy based on transthoracic needle biopsy specimen was 88%. The sensitivity was 93%. P829 scintigraphy correctly identified or excluded malignancy in 27 of 30 subjects.. P829 scintigraphy reliably identified or excluded malignancy in radiographically indeterminate solitary pulmonary nodules. The sensitivity and specificity compared favorably with the reported results of F-18 fluorodeoxyglucose positron emission tomographic imaging.

Topics: Adult; Aged; Biopsy; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Contrast Media; Female; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Peptides, Cyclic; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity; Solitary Pulmonary Nodule; Technetium; Tomography, Emission-Computed, Single-Photon

Gene therapy protocols require better modalities to monitor the location and level of transferred gene expression. One potential in vivo mechanism to assess gene expression would be to image the binding of a radiolabeled peptide to a reporter receptor that is expressed in targeted tissues. This concept was tested in a tumor model using a replication-incompetent adenoviral vector encoding the human type 2 somatostatin receptor (Ad5-CMVhSSTr2). Expression of the hSSTr2 reporter was imaged using a radiolabeled, somatostatin-avid peptide (P829).. Bilateral subcutaneous A427 tumor xenografts were established on the flanks of athymic nude mice. These human-origin, non-small cell lung tumors are normally negative for hSSTr2 expression. One tumor was injected directly with Ad5-CMVhSSTr2, whereas the second tumor was injected directly with a control Ad5 vector. The mice were injected intravenously 48 h later with P829 peptide that was radiolabeled to high specific activity with 99mTc (half-life, 6 h) or 188Re (half-life, 17 h). Tumors were frozen and evaluated for somatostatin receptor expression using fluorescein-labeled somatostatin.. The accumulation of radiolabeled P829 in hSSTr2-expressing tumors was easily visualized by gamma camera imaging 3 h after injection. Imaging region of interest analyses and biodistribution studies confirmed a 5- to 10-fold greater accumulation of both radiolabeled P829 peptides in the Ad5-CMVhSSTr2-injected tumors versus control tumors injected with control Ad5 vectors. Ad5-CMVhSSTr2-injected tumors accumulated 2.5-3.8 percentage injected dose per gram 3 h after injection. Only Ad5-CMVhSSTr2-injected tumors expressed somatostatin receptors, as determined by immunohistochemistry.. These studies show the feasibility of imaging a 99mTc-labeled peptide's binding to a reporter receptor after in vivo gene transfer to tumor cells. The 188Re-labeled peptide worked equally well for this imaging approach and offers the additional advantage of energetic beta decay with potential therapeutic efficacy. 99mTc and 188Re are generator produced, an advantage for widespread availability and low cost, and both radioisotopes can be imaged with existing, high-resolution modalities. There is great potential for using 99mTc-labeled peptides for imaging gene transfer with the hSSTr2 reporter receptor, especially when the reporter correlates with the expression of therapeutic genes that can be included simultaneously in the gene therapy vector.

Topics: Adenoviridae; Animals; Female; Gene Expression; Gene Transfer Techniques; Genetic Vectors; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Peptides, Cyclic; Radioisotopes; Receptors, Somatostatin; Rhenium; Technetium; Tumor Cells, Cultured

Topics: Breast Neoplasms; Contrast Media; Drug Approval; Female; Humans; Lung Neoplasms; Organotechnetium Compounds; Peptides, Cyclic; Radionuclide Imaging