Radiolabeled CCK/gastrin peptides for imaging and therapy of CCK2 receptor-expressing tumors

Cholecystokinin (CCK) receptors are overexpressed in numerous human cancers, like medullary thyroid carcinomas, small cell lung cancers and stromal ovarian cancers. The specific receptor-binding property of the endogenous ligands for these receptors can be exploited by labeling peptides with a radionuclide and using these as carriers to guide the radioactivity to the tissues that express the receptors. In this way, tumors can be visualized using positron emission tomography and single photon emission computed tomography imaging. A variety of radiolabeled CCK/gastrin-related peptides has been synthesized and characterized for imaging. All peptides have the C-terminal CCK receptor-binding tetrapeptide sequence Trp-Met-Asp-Phe-NH2 in common or derivatives thereof. This review focuses on the development and application of radiolabeled CCK/gastrin peptides for radionuclide imaging and radionuclide therapy of tumors expressing CCK receptors. We discuss both preclinical studies as well as clinical studies with CCK and gastrin peptides

Necrotizing fasciitis in children: Prompt recognition and aggressive therapy improve survival

Necrotizing fasciitis (NF) is a bacterial infection of the soft tissues with a fulminant course and a high mortality rate. The authors performed a review to define the diagnosis, bacteriology, and management of NF in the pediatric population. This report of 20 cases treated over 18 years represents the largest reported pediatric experience. These infections were attributable to secondary infection of varicella lesions (5), omphalitis (4), extremity lesions (4), perineal infections (3), head and neck lesions (2), inguinal herniorrhapy (1), and breast abscess (1). Nineteen of the 20 children were healthy, without chronic disease or immunosuppression. All patients presented with an altered sensorium and signs of systemic toxicity. Fever (40%), tachycardia (70%), and abnormal white blood cell count (50%) were not uniformly present. There was marked tissue edema in all patients, with a characteristic peau d\u27orange appearance in 18. Seven infections were caused by streptococcus; the remainder were polymicrobial, involving multiple aerobes and anaerobes. Initial gram stain was of limited utility; in 14 of 19 cases the result was negative or showed only one of many organisms present. Fifteen patients survived and five died. All survivors underwent aggressive surgical debridement within 3 hours of admission. The survivors required of a mean of 3.8 operations. Fascial excision of up to 35% of total body surface area was required. One patient required amputation, two had colostomies, and six required extensive skin grafting for reconstruction. All five patients who died had delayed initial management. Conclusion: NF is a serious cause of death in previously healthy children. The diagnosis should be considered in the presence of any soft tissue infection presenting with signs of toxicity and marked wound edema, even in the absence of fever or abnormal white blood cell count. Immediate surgical debridement and coverage with penicillin, an aminoglycoside, and metronidazole are essential. Subsequent changes in antibiotics should be based on culture data because gram stain results are not reliable. More than one operation is required in almost all cases