RP463: a stabilized technetium-99m complex of a hydrazino nicotinamide derivatized chemotactic peptide for infection imaging.

A HYNIC-conjugated chemotactic peptide (fMLFK-HYNIC) was labeled with (99m)Tc using tricine and TPPTS as coligands. The combination of fMLFK-HYNIC, tricine, and TPPTS with (99m)Tc produced a ternary ligand complex [(99m)Tc(fMLFK-HYNIC)(tricine)(TPPTS)] (RP463). RP463 was synthesized either in two steps, in which the binary ligand complex [(99m)Tc(fMLFK-HYNIC)(tricine)(2)] (RP469) was formed first and then reacted with TPPTS, or in one step by direct reduction of [(99m)Tc]pertechnetate with stannous chloride in the presence of fMLFK-HYNIC, tricine, and TPPTS. The radiolabeling yield for RP463 was usually >/=90% using 10 microg of fMLFK-HYNIC and 100 mCi of [(99m)Tc]pertechnetate. Unlike RP469, which decomposed rapidly in the absence of excess tricine coligand, RP463 was stable in solution for at least 6 h. [(99)Tc]RP463 was prepared and characterized by HPLC and electrospray mass spectrometry. In an in vitro assay, [(99)Tc]RP463 showed an IC(50) of 2 nM against binding of [(3)H]fMLF to receptors on PMNs. [(99)Tc]RP463 also induces effectively the superoxide release of polymorphonuclear leukocytes (PMNs) with an EC(50) value of 0.2 +/- 0.2 nM. The localization of RP463 in the infection foci was assessed in a rabbit infection model. RP463 was cleared from the blood faster than RP469 and was excreted mainly through the renal system. As a result of rapid blood clearance and increased uptake, the target-to-background ratios continuously increased from 1.5 +/- 0.2 at 15 min postinjection to 7.5 +/- 0.4 at 4 h postinjection. Visualization of the infected area could be as early as 2 h. A transient decrease in white blood cell count of 35% was observed during the first 30 min after injection of the HPLC-purified RP463 in the infected rabbit. This suggests that future research in this area should focus on developing highly potent antagonists for chemotactic peptide receptor or other receptors on PMNs and monocytes.

Biological evaluation of thrombus imaging agents utilizing water soluble phosphines and tricine as coligands when used to label a hydrazinonicotinamide-modified cyclic glycoprotein IIb/IIIa receptor antagonist with 99mTc.

A hydrazinonicotinamide-functionalized cyclic glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist [cyclo(D-Val-NMeArg-Gly-Asp-Mamb(5-(6-(6-hydrazinonicotin amido)hexanamide))) (HYNICtide)] was labeled with 99mTc using tricine and a water soluble phosphine [trisodium triphenylphosphine-3,3',3"-trisulfonate (TPPTS); disodium triphenylphosphine-3,3'-disulfonate (TPPDS); or sodium triphenylphosphine-3-monosulfonate (TPPMS)] as coligands. Three complexes, [99mTc(HYNICtide)(L)(tricine)] (1, L = TPPTS; 2, L = TPPDS; 3, L = TPPMS), were evaluated in the canine arteriovenous shunt (AV shunt) model and canine deep vein thrombosis imaging (DVT) model. All three agents were adequately incorporated into the arterial and venous portions of the growing thrombus (7.8-9.9 and 0.2-3.7% ID/g, respectively) in the canine AV shunt model. In the canine DVT model all three complexes had thrombus uptake that far exceeded the negative control, [99mTc]albumin. The findings indicate similar incorporation into a venous thrombus (% ID/g = 2.86 +/- 0.4, 3.4 +/- 0.9, and 3.38 +/- 1.1 for complexes 1, 2, and 3, respectively) and similar blood clearance with a t1/2 of approximately 90 min. Gamma camera scintigraphy allowed visualization of deep vein thrombosis in as little as 15 min with the thrombus/muscle ratios being 3.8 +/- 0.8, 2.8 +/- 0.4, and 3.0 +/- 0.8 for complexes 1, 2, and 3, respectively. The visualization of the thrombus improved over time, and the thrombus/muscle ratios were 9.7 +/- 1.9, 13.8 +/- 3.6, and 9.4 +/- 2 for complexes 1, 2, and 3, respectively, at 120 min postinjection. The administration of complexes 1-3 did not alter platelet function, hemodynamics, or the coagulation cascade. Furthermore, complexes 1-3 did not significantly differ in their uptake into the growing thrombus, blood clearance, and target to background ratios. Therefore, all three complexes have the capability to detect rapidly growing venous and arterial thrombi.

Data collection for the evaluation of mental retardation prevention activities: the fateful forty-three.

A schema for measuring the effects of prevention programs in mental retardation was presented using items that are quantifiable, accessible, and pertinent to disability outcomes. These elements relate to interventions in the prenatal, perinatal, and childhood periods. They also reflect improvements in agency systems. The items were classified as service indicators, risk indicators, and incidence/prevalence information. The list is called "The Fateful Forty-Three" because of its intimate alliance with the stakes for children now and in the future. Representative data were given for these components, as were the sources for gathering such information. The inventory was proposed to be used as a program checklist and a base for discussion and planning.

Head circumference of children with Down syndrome (0-36 months)

This study provides statistically appropriate head circumference reference curves for males and females with Down syndrome (DS) from birth to 36 months of age. A total of 239 males and 182 females from five study populations, yielding a combination of cross-sectional and longitudinal data, were used for the analysis. The method of least squares was used to test the fit of the growth model y = a+bx+c[log(x + 1)], where x is age in months. These standardized curves should provide information of value in the medical, physical, and developmental management of children with DS.

The challenge of "Healthy People 2000".

The federal Office of Disease Prevention and Health Promotion (U.S. Public Health Service) has again prepared a compilation of goals and objectives for the health of the Nation's people, applicable to anticipated achievements within the decade ending in the year 2000. This effort involved work groups from numerous federal agencies, testimony in regional hearings from 800 citizens, and enrollment of a consortium of 300 national organizations. The final product, "Healthy People 2000," was released in September 1990, and contains 298 measurable objectives. Content regarding children, genetic disorders, developmental disabilities, and disabilities in general is less featured and less specific than was hoped for. Ten objectives of relatively direct concern to geneticists are discussed, plus 23 others of interest in the maternal and child health field. On balance, it is suggested that the Healthy People 2000 objectives can be useful and stimulating for workers in genetics, child health care, and disabilities' services. Regrettably, there was no simultaneous proposal of legislation that would provide new federal programs, funding, or assistance to states.

Developmental services for children with HIV infection.

The significant developmental special needs of young children with congenital HIV infection require evaluation, training and education, therapy, and other supports. These services would usually be guided by developmentalists in a child study center, who are in close alliance with the medical, educational, and community service components of child and family care. Concerns about the infectiousness of these children are manageable and not a major threat in the setting of developmental services.

Perceived needs of families with children who have chronic health conditions.

Parents of children with a wide variety of chronic health conditions (N = 910) were surveyed about their use of health services, out-of-pocket expenses for health care and related items, and ratings of the importance of health and support services. The financial burden on this middle-class, insured sample was substantial, with about half indicating some out-of-pocket expenses for travel, parking fees, drugs and medication, bills after insurance payments, and doctor charges. The commonalities found in parents' reporting of important services needed support the use of a noncategorical approach to program planning and policy development for children with special health care needs.