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We propose a renal imaging agent, the 99m Tc complex of the bidentate- N ,S chelate N -(mercaptoacetyl) glycine ( 99m Tc-2GAM), with the imaging characteristics of 99m Tc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of 99m Tc-2GAM as [Tc V (O)(GAM) 2 ] − . After biodistribution and toxicity studies in animals, 99m Tc-2GAM was evaluated in five normal volunteers. 99m Tc-2GAM is rapidly cleared from the blood (t12 = 9 min) and 50% of the ID is excreted in the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No significant activity is detected in other organs. We showed no differences between 99m Tc-2GAM and 99m Tc-DMSA compared in three patients with unilateral kidney disease. We conclude that 99m Tc-2GAM has good practical and dosimetric features for renal imaging.

Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is an aberrant fusion gene product expressed in a subset of cases of anaplastic large cell lymphoma (ALCL). It has been shown that NPM-ALK binds to and activates signal transducer and activator of transcription 3 (STAT3) in vitro, and that STAT3 is constitutively active in ALK(+) ALCL cell lines and tumors. In view of the oncogenic potential of STAT3, we further examined its biological significance in ALCL using two ALK(+) ALCL cell lines (Karpas 299 and SU-DHL-1) and an adenoviral vector that carries dominant-negative STAT3 (AdSTAT3DN). Infection by AdSTAT3DN led to the expression of STAT3DN in both ALK(+) ALCL cell lines at a similar efficiency. Subcellular fractionation studies showed that a significant proportion of the expressed STAT3DN protein translocated to the nucleus, despite the fact that STAT3DN has a mutation at residue 705(tyrosine --> phenylalanine), a site that is believed to be crucial for STAT3 activation and nuclear translocation. Introduction of STAT3DN induced apoptosis and G(1) cell cycle arrest. Western blot studies showed that expression of STAT3DN resulted in caspase-3 cleavage, downregulation of Bcl-2, Bcl-xL, cyclin D3, survivin, Mcl-1, c-Myc and suppressor of cytokine signaling 3. These results support the concept that STAT3 activation is pathogenetically important in ALCL cells by deregulating the expression of multiple target proteins that are involved in the control of apoptosis and cell cycle progression.