Biodistribution and Hepatic Metabolism of Galactosylated 111In-Antibody-Chelator Conjugates: Comparison with 111In-Antibody-Chelator Conjugates / 대한핵의학회잡지

PURPOSE: To evaluate the use of monoclonal antibody (MoAb) as a carrier of the receptor-binding ligand, the receptor mediated uptake into liver and subsequent metabolism of (111) In-labeled galactosylated MoAb-chelator conjugates were investigated and compared with those of (111) In labeled MoAb. MATERIALS AND METHODS: T101 MoAb, IgG2 against human lymphocytic leukemic cell, conjugated with cyclic DTPA dianhydride (DTPA) or 2-p-isothiocyanatobenzyl-6-methyl-DTPA (1B4M) was galactosylated with 2-imino-2-methoxyethyl-1-thio-beta-D-galactose and then radiolabeled with (111) In. Biodistribution and metabolism study was performed with two (111) In-conjugates in mice and rats. RESULTS: (111) In-labeled T101 and its galactosylated conjugates were taken to the liver by the time, mostly within 10 min. However DTPA conjugate was retained longer in the liver than the 1B4M conjugate (55% vs 20% of injected dose at 44 hr). During this time, the radiometabolite of DTPA conjugate was excreted similarly into urine (24%) and feces (17%). The radiometabolite of 1B4M was excreted primarily into feces (68%) rather than urine (8%). Size exclusion HPLC analysis of the bile and supernatant of liver homogenate showed two peaks, the first (35%) with the retention time (Rt) identical to IgG and the second (65%) with Rt similar to free 111In at 3 hr post-injection for the 1B4M conjugate, indicating that the metabolite is rapidly excreted through the biliary system. In contrast to DTPA conjugate, the small (111) In-DTPA-like metabolite was the major radioindium component (90%) in the liver homogenate as early as 3 hour post-injection, but the cumulative radioindium activity in feces was only 17% at 44 hour, indicating that the metabolite from DTPA conjugate does not clear readily through the biliary tract. CONCLUSION: The galactosylation of the MoAb conjugates resulted in higher hepatocyte uptake and enhanced metabolism, compared to those without galactosylation. Metabolism of the MoAb-conjugates is different between compounds radiolabled with different chelators due to different characteristics of radiometabolites generated in the liver.

CT Findings of Primary Malignant Pulmonary Mesenchymal Tumors

PURPOSE: To describe the CT findings and charicteristic clinical manifestation of primary malignant pulmonarymesenchymal tumors. MATERIALS AND METHODS: This study involved nine histopathologically proven cases of malignantprimary pulmonary mesenchymal tumors, as follows : MFH(n=2), leiomyosarcoma(n=2), pulmonary blastoma(n=1),neurogenic sarcoma(n=1), rhabdomyosarcoma(n=1), liposarcoma(n=1) and hemangiopericytoma(n=1). Two patients weremale and seven were female; their median age was 45. We retrospectively analyzed tumor size, location,characteristic of the peripheral margin, relationship to airways, and whether there was distal atelectasis orobstructive pneumonitis and lymph node involvement. We also reviewed distant metastasis, tumor growth rate and theinterval between surgery and recurrence, as seen on follow-up CT scans(n=6). RESULTS: Lesions were located at theright upper (n=2), right middle (n=1), right lower (n=1) and left lower lobe (n=2); in three cases, the whole leftlung (left upper + left lower lobe) was involved. CT findings showed that in all cases, the largest diameter ofmasses ranged from 3 to 15 cm; a well-demarcated margin was seen (smooth in eight cases, psiculated in one) andthis was well enhanced(inhomogeneous in six cases, homogeneous in three). In six cases, masses encircled ordisplaced the peritumoral small bronchus, and in five cases, were located in the peripheral lung field. In fourpatients who underwent endobronchoscopy, no endobronchial lesions were present, and in six cases scans initial CTscans showed no lymph-node involvement. In two cases, mass size doubled within one month. On initial diagnosis,distant metastasis was seen in seven cases, and in three, recurrent lesions were detected within postoperative sixmonths. CONCLUSION: If in the differential diagnosis of lung cancer, a mass seen on CT images is well demarcated,large, peripheral, inhomogeneously enhanced, encircles or displaces the peritumoral small bronchus, shows earlydistant metastasis, is high locally invasive, and recurs early with relative sparing of the lymph nodes, thepossibility of primary malignant pulmonary mesenchymal tumor shouldbe considered.