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J Powe

Publications and source records attributed to J Powe.

44 records · Page 3Linked to original sources

Inhibition of human tumor growth by IgG2A monoclonal antibodies correlates with antibody density on tumor cells.

Eight monoclonal antibodies (MAb) of IgG2a isotype that were produced against human melanomas were tested for tumor growth-inhibiting properties in nude mice injected with human melanoma cells of various origins. Four of the eight MAb inhibited growth of these tumors, and all four of these antibodies reacted in antibody-dependent macrophage-mediated cytotoxicity (ADMC) assays in vitro. The MAb that were inactive in vivo also did not react in these assays in vitro. The number of antibody-binding sites per cell on the tumor cell surface was significantly higher for tumoricidal MAb as compared to unreactive MAb. On the other hand, the percentage of tumor cells binding the MAb and the binding affinity to these cells were the same for the two groups of MAb. Also, tumoricidal and nontumoricidal MAb bound with similar affinity and antibody density to Fc receptors on macrophages. The importance of the number of antibody sites on the tumor cell surface for tumor destruction by MAb was confirmed by the demonstration of tumoricidal effects of mixtures of MAb that were by themselves not tumoricidal. MAb binding to different molecules on melanoma cells were complementary in ADMC, whereas MAb directed to the same molecule but to different epitopes were not.

Animals↗

Labeling monoclonal antibodies and F(ab')2 fragments with (111In) indium using cyclic DTPA anhydride and their in vivo behavior in mice bearing human tumor xenografts.

Monoclonal antibodies (MAb) and their F(ab')2 fragments to human colorectal carcinoma (CRC) and human melanoma-associated antigens were conjugated to diethylenetriaminepentaacetic acid (DTPA) via an acylation reaction using cyclic DTPA dianhydride. Relative immunoreactivity of the F(ab')2 fragments was as high as 70% when an average of only 0.7 DTPA molecules was conjugated per fragment, decreasing rapidly to less than 5% when 9.0 DTPA molecules were conjugated. The 111In-labeled whole MAb in mice bearing human tumor xenografts showed higher concentrations in tumor, liver, kidney, and spleen 7 days after injection of MAb when compared with the same MAb labeled with 131I. F(ab')2 labeled with 111In showed a marked persistence in the tumor-bearing mice with higher concentrations in all organs except blood, when compared with 131I-labeled F(ab')2. Radioactivity was particularly high in the kidneys. Although images of human tumor xenografts were easily visualized using 131I-labeled F(ab')2 3 days after injection, it was difficult to visualize tumor grafts with 111In-labeled F(ab')2 due to persistently high renal, liver, and background activity. Increased catabolism of the 131I-labeled MAb may be the cause of the difference; but antibodies with high immunological activity are a necessity for in vivo imaging studies before firm conclusions can be drawn.

Animals↗

Metastatic colon carcinoma detected with radiolabeled F(ab')2 monoclonal antibody fragments.

Nine patients with colonic carcinoma were studied with I-131-labeled F(ab')2 fragments of an anti-colorectal carcinoma monoclonal antibody. A total of 69% of colon cancer sites were detected without background subtraction; metastases from a concurrent breast carcinoma in one patient were not seen. Lesions ranged from 1.5 to 8 cm. The mean thyroid uptake of I-131 at 24 hours was 0.25%. Half-lives of I-131 in the blood (protein-bound and total) fit a two-compartment model, with half-lives of 3.5 and 27.6 hours for the protein-bound fraction and 3.6 and 23.8 hours for total I-131. Using quantitative methods, a mean value of 0.0047%/cm3 of the administered dose was localized in the tumor at peak concentration, which occurred approximately 48 hours post-administration. This has implications for therapy planning.

Antibodies, Monoclonal↗

Radioimmunodetection of human tumor xenografts by monoclonal antibodies.

Mouse IgG2a monoclonal antibodies with specific binding reactivity in vitro to human tumors of the gastrointestinal tract were radioiodinated and injected into immunosuppressed mice xenografted with human colon carcinoma tumors. The antibodies preferentially localized in tumor tissue compared to normal mouse tissue, as determined by differential tissue counting of radioactivity. Preferential antibody localization in tumor tissue was greatly enhanced when F(ab')2 fragments of the antibodies were used, and the fragments localized specifically only in those tumors that bind the antibodies in vitro and not in unrelated tumors. Radiolabeled fragments of an anti-hepatitis virus monoclonal antibody of the same isotype as the specific antibody did not localize in tumors. Tumors could be located by whole-body gamma-scintigraphy with radiolabeled specific antibody F(ab')2 fragments without background subtraction.

Animals↗

Factors influencing DTPA conjugation with antibodies by cyclic DTPA anhydride.

Diethylenetriaminepentaacetic acid (DTPA) was conjugated with a practical concentration (300 micrograms/ml) of antibody to human albumin (Ab) and 1083 17-1A monoclonal colorectal antibody (MAb-17-1A) via an acylation reaction using cyclic DTPA anhydride (cDTPAA). The conjugation reaction was favored as pH increased. Bicarbonate buffer at pH 8.2 was chosen for studies of the effect of the cDTPAA-to-antibody ratio on DTPA conjugation with antibody because of its good buffer capacity at that pH. The reaction of cDTPAA with Ab at molar ratios of 2000, 1000, 500, and 100 in the bicarbonate buffer gave rise to 11, 9, 8, and 2 indium atoms incorporated per Ab with 47%, 55%, 59%, and 77% retention of the binding activity. For the conjugation reaction of MAb-17-1A, 29, 28, 31, 11, 4, and 1 indium atoms were incorporated, with the retention of less than 5%, less than 5%, less than 5%, 12%, 60%, and 93% of binding activity when the molar ratio was 5000, 2000, 1000, 500, 100, and 50.

Animals↗

Radioiodine uptake in the head and neck.

OBJECTIVE: To report two cases of sinusitis-associated radioiodine uptake in patients with thyroid cancer and to review the reported causes of false-positive radioiodine uptake in the head and neck area. METHODS: We present the radiologic findings in two patients who had undergone treatment for papillary thyroid cancer and discuss other settings in which radioiodine uptake suggested the presence of metastatic disease. RESULTS: Radioiodine whole-body scans of two patients who had had thyroid cancer demonstrated uptake in the sphenoid and maxillary sinuses, respectively, mimicking bone or brain metastatic involvement. The thyroglobulin levels were low. Computed tomographic (CT) scanning disclosed mucosal swelling in the sinuses, consistent with sinusitis. The radioiodine uptake cleared on a follow-up scan in one case and was more localized than the CT findings in the other. Eighteen causes of false-positive radioiodine uptake in the head and neck area have been reported. On the basis of the mechanism of uptake, they can be classified into four categories: (1) physiologic uptake (ectopic thyroid tissue), (2) nonthyroidal pathologic conditions (dacryocystitis, sinusitis, sinus mucocele, sialadenitis, folliculitis, Warthin's tumor, parotid cyst, porencephaly, posttraumatic cerebromalacia, and inflammation due to dental disease or a nose ring), (3) internal retention (ectasia of the carotid artery and an artificial eye), and (4) external contamination by body secretions (sweat and nasal, tracheobronchial, lacrimal, and salivary secretions). The estimated prevalence of external contamination in the head and neck area on whole-body radioiodine scans is 0.3%. CONCLUSION: Physicians should rule out the presence of radioiodine uptake by inflamed mucosa of the paranasal sinuses, as well as various other causes of false-positive radioiodine uptake, before metastatic thyroid cancer in the head and neck area is diagnosed.

Carcinoma, Papillary↗