Comparison of anti-Tac and anti-transferrin receptor-conjugated liposomes for specific drug delivery to adult T-cell leukemia

Adult T-cell leukemia (ATL) is a rapidly progressive and usually fatal malignancy of mature T cells characterized by the expression of large numbers of interleukin-2 (IL-2) receptors on the cell surface. Anti- Tac, a monoclonal antibody directed against the IL-2 receptor, was conjugated to liposomes and compared with anti-transferrin receptor (anti-TFR) conjugates for specific binding, internalization, and intracellular drug delivery to ATL cells. Two independent assays were used: a fluorimetric assay with liposome encapsulated 1-hydroxypyrene- 3,6,8-trisulfonic acid, a pH-sensitive fluorescent dye, and a growth inhibition assay using methotrexate-gamma-aspartate, a liposome- dependent cytotoxic drug. MT-1 and HUT-102 cell lines derived from patients with ATL were compared with Molt-4, a leukemia cell line that does not express IL-2 receptors in an uninduced state. Fluorimetric studies showed specific binding and internalization of anti-Tac- conjugated liposomes by HUT-102 and MT-1 but not by the Tac-negative cell line Molt-4, demonstrating the lack of nonspecific or Fc receptor- mediated uptake. Anti-TFR-conjugated liposomes were effectively bound and internalized by all three cell lines and consistently showed the highest degree of cellular liposome uptake. Drug-containing liposomes conjugated to anti-Tac were more than tenfold more effective in causing growth inhibition of ATL cells than the nonspecific control conjugates. Anti-Tac conjugates caused minimal growth inhibition of Molt-4 cells over the concentration range effective against the ATL cells. Anti-TFR- coupled liposomes gave better growth inhibition of HUT-102 and MT-1 cells (40- to 60-fold) than anti-Tac conjugates. Both anti-Tac-directed and anti-TFR-directed liposomes are effective for intracellular drug delivery to ATL cells and may represent a useful method of treatment in this disease.     

Cerebrovascular disease: evaluation with transbrachial intraarterial digital subtraction angiography using a 4-F catheter

Three hundred sixty-one patients underwent intraarterial digital subtraction angiography for definite or probable occlusive vascular disease of the carotid arteries. Examinations were performed with 65-cm-long, 4-F aortic catheters. A transbrachial approach was used. Images were good or excellent in nearly all cases. No postprocedural neurologic deficits or hematomas occurred. Permanent pulse deficit occurred in two patients, and temporary deficit occurred in three patients, an improvement over the frequency found in previous transbrachial series using 6-8-F catheters. While these results establish the efficacy of this technique, they also indicate a possible greater relative safety in men than in women.     

von Hippel-Lindau disease: inadequacy of angiography for identification of renal cancers

Selective renal angiograms were retrospectively evaluated for the identification of renal cell cancers in patients with von Hippel-Lindau disease (VHL). Seven patients underwent angiography and surgery because of solid or complex renal masses identified at cross-sectional imaging. Nine kidneys underwent detailed examination by the surgeon and by a pathologist. There were 31 renal cancers. Angiography had enabled identification of only five cancers (16%), and six others (19%) had been suspected. Cancers detected angiographically were larger than those not detected (P less than .05). Solid tumors tended to appear less hypervascular than expected and occasionally had the angiographic appearance of atypical cysts. There were no false-positive angiograms. Angiography revealed only one cancer not previously suspected and changed the surgeon's approach for only one kidney (11%). The sensitivity and specificity of angiography were 35% and 100%, respectively. In these patients, selective renal angiography is not helpful for the detection or exclusion of cancer in a kidney. It does not have a limited role for vascular mapping prior to partial nephrectomy or tumor enucleation.