Lotze M T, Carrasquillo J A, Weinstein J N, Bryant G J, Perentesis P, Reynolds J C, Matis L A, Eger R R, Keenan A M, Hellström I
Ann Surg. 1986 Sep;204(3):223-35. doi: 10.1097/00000658-198609000-00002.
Fab fragments of monoclonal antibodies (MoAb) to melanoma, radiolabeled with 131I, were evaluated as diagnostic reagents to determine their ability to localize systemic--MoAb injected intravenously (IV)--or nodal metastatic disease--injected subcutaneously (SQ) at a site proximal to draining lymph nodes. Sixty-one scans were performed (40 IV, 21 SQ) in 59 patients who had injections of 0.2-50 mg of 131I coupled (0.2-12 mCi) antibody. These included 48.7, which identifies a high molecular weight antigen (HMW), or 96.5, which identifies a transferrin like molecule, p97. 125I coupled nonspecific Fab 1.4, reacting with murine leukemia virus, or the whole antibody BL3, reactive with a human B cell idiotypic determinant, was generally used in tandem with the patients injected SQ as a nonspecific control. All patients had immunohistochemical studies performed on biopsied lesions and demonstrated binding to the antibodies injected. Of the IV patients, 22/38 (58%) had (+) scans, 13 at SQ or nodal sites, four at visceral sites, and five at visceral and SQ sites. Patients with clinical stage II disease had SQ injection of MoAb, including 11 additional patients injected with the whole antibody 9.2.27 (anti-HMW) labeled with 111In (6 patients) or 131I (5 patients). Nodal dissection was performed 2-4 days later. All 111In coupled antibodies demonstrated excellent nodal delineation without specific identification of tumor deposits. Of the 21 patients injected SQ with MoAb, 17 had confirmed tumor in nodes. Of patients injected with Fab fragments, 4/8 (50%) had specific uptake of MoAb, although only two were successfully imaged. Increased uptake of antimelanoma antibodies was observed in some patients in lymph nodes not containing tumor and was possibly related to antigen shedding. Clearance of labeled antibody from the injection site occurred with a half life of 16-50 hours. Toxicity was limited to local discomfort at the site of SQ injection. Melanoma metastases can be identified with IV or SQ injection or radiolabeled antibodies. These reagents may be useful in the diagnosis or therapy of human melanoma. Further evaluation will be required before they could be considered clinically useful.
用¹³¹I 进行放射性标记的抗黑色素瘤单克隆抗体(MoAb)的 Fab 片段,作为诊断试剂进行评估,以确定其定位全身——静脉注射(IV)MoAb——或淋巴结转移疾病——在引流淋巴结近端部位皮下注射(SQ)的能力。对 59 名患者进行了 61 次扫描(40 次 IV,21 次 SQ),这些患者注射了 0.2 - 50 mg ¹³¹I 偶联(0.2 - 12 mCi)的抗体。这些抗体包括识别高分子量抗原(HMW)的 48.7 或识别转铁蛋白样分子 p97 的 96.5。与鼠白血病病毒反应的¹²⁵I 偶联非特异性 Fab 1.4 或与人 B 细胞独特型决定簇反应的全抗体 BL3,通常与皮下注射的患者串联使用作为非特异性对照。所有患者对活检病变进行了免疫组织化学研究,并显示与注射的抗体结合。静脉注射的患者中,22/38(58%)扫描结果为阳性,13 例在皮下或淋巴结部位,4 例在内脏部位,5 例在内脏和皮下部位。临床 II 期疾病患者进行了 MoAb 的皮下注射,包括另外 11 例注射了用¹¹¹In(6 例)或¹³¹I(5 例)标记的全抗体 9.2.27(抗 HMW)的患者。2 - 4天后进行淋巴结清扫。所有¹¹¹In 偶联抗体均显示出出色的淋巴结轮廓,但未特异性识别肿瘤沉积物。在 21 例皮下注射 MoAb 的患者中,17 例在淋巴结中证实有肿瘤。在注射 Fab 片段的患者中,4/8(50%)有 MoAb 的特异性摄取,尽管只有 2 例成功成像。在一些不含肿瘤的淋巴结中观察到抗黑色素瘤抗体摄取增加,可能与抗原脱落有关。标记抗体从注射部位清除的半衰期为 16 - 50 小时。毒性仅限于皮下注射部位的局部不适。黑色素瘤转移灶可通过静脉注射或皮下注射放射性标记抗体来识别。这些试剂可能对人类黑色素瘤的诊断或治疗有用。在它们被认为具有临床实用性之前,还需要进一步评估。