Purpose: The therapeutic efficacy of a unique melanoma-targeting peptide conjugated with an in vivo generated a-particle-emitting radionuclide was evaluated in the B16/F1mouse melanoma animal model. a-Radiation is densely ionizing, resulting in high concentrations of destructive radicals and irreparable DNA double-strand breaks. This high linear energy transfer overcomes radiation-resistant tumor cells and oxygen effects resulting in potentially high therapeutic indices in tumors such as melanoma.

Peptide-targeted a-therapy with 7.4 MBq of 212 Pb-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-ReO-[Cys 3,4,10 , D-Phe 7 ,Arg 11 ]a-MSH 3-13 ( 212 Pb-DOTA-Re(Arg 11 )CCMSH) cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-d study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patientspecific dosimetry and to monitor the tumor response to 212 Pb-DOTA-Re(Arg 11 )CCMSH therapy. The purpose of this study was to evaluate the potential of 203 Pb-DOTA-Re(Arg 11 )CCMSH as a matched-pair SPECT agent for 212 Pb-DOTA-Re(Arg 11 ) CCMSH. Methods: DOTA-Re(Arg 11 )CCMSH was labeled with 203 Pb in 0.5 M NH 4 OAc buffer at pH 5.4. The internalization and efflux of 203 Pb-DOTA-Re(Arg 11 )CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of 203 Pb-DOTARe(Arg 11 )CCMSH was examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT study was performed with 203 Pb-DOTA-Re(Arg 11 )CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h after injection. Results: 203 Pb-DOTARe(Arg 11 )CCMSH was easily prepared in NH 4 OAc buffer and completely separated from the excess nonradiolabeled peptide by reversed-phase high-performance liquid chromatography (RP-HPLC). 203 Pb-DOTA-Re(Arg 11 )CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of 203 Pb-DOTA-Re(Arg 11 )CCMSH activity internalized after a 20-min incubation at 25°C. After incubation of the cells in culture medium for 20 min, 78% of internalized activity remained in the cells. 203 Pb-DOTA-Re(Arg 11 )CCMSH exhibited a biodistribution pattern similar to that of 212 Pb-DOTA-Re(Arg 11 )CCMSH in B16/ F1 melanoma-bearing mice. 203 Pb-DOTA-Re(Arg 11 )CCMSH exhibited a peak tumor uptake of 12.00 6 3.20 percentage injected dose per gram (%ID/g) at 1 h after injection. The tumor uptake gradually decreased to 3.43 6 1.12 %ID/g at 48 h after injection. 203 Pb-DOTA-Re(Arg 11 )CCMSH exhibited a peak tumor-to-kidney uptake ratio of 1.53 at 2 h after injection. The absorbed doses to the tumor and kidneys were 4.32 and 4.35 Gy, respectively, per 37 MBq. Whole-body clearance of 203 Pb-DOTA-Re(Arg 11 )CCMSH was fast, with approximately 89% of the injected activity cleared through the urinary system by 2 h after injection. 203 Pb showed 1.6-mm SPECT resolution, which was comparable to 99m Tc. Melanoma lesions were visualized through SPECT/CT images of 203 Pb-DOTA-Re(Arg 11 )CCMSH at 2 h after injection. Conclusion: 203 Pb-DOTA-Re(Arg 11 )CCMSH exhibited favorable pharmacokinetic and tumor imaging properties, highlighting its potential as a matched-pair SPECT agent for 212 Pb-DOTA-Re(Arg 11 )CCMSH melanoma treatment.

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Every employee is a problem employee, just as every child in a home is a problem child; every personality that is added to an organization means an increase in the number of problems that the personnel department must meet, and in the number of tense situations that may develop. Every employee is a potential disturber of industrial peace, and a probable victim of the interplay of emotional and rational forces that may be brought to bear upon him. SOURCES OF DISSATISFACTION IN INDUSTRYIn every organization there are forces which are constant or oftrecurring sources of dissatisfaction and which may readily create problem situations. Whiting Williams 1 lists the most common causes as follows:a. The lack of security on the job, due to some sort of seniority rules based upon length of service.b. A complicated pay system which makes it impossible for workers to understand how much they are making. c. A foreman doing things that he should not do.d. An inactive shop committee. e. Too many promises made and broken by management. /. Inadequate differentials in the pay of the unskilled, semiskilled, and skilled workers.Whitehead 2 adds two other factors which are frequent causes of industrial unrest: a. Unwarranted and apparently unreasonable changes in work. b. A threatened unbalance of the social relations within a group. Other Types of Undesirable Employees.-These are indicated in the reasons that are offered by personnel managers for the discharge of employees. Table 124 gives the results from two studies, one made by T. T. Reed 3 in a large department store, and the other made by J. M. Brewer 4 in a summary of the reasons why industrial organizations discharged 4,375 employees.