Synthesis and biologic evaluation of 64Cu-labeled rhenium-cyclized alpha-MSH peptide analog using a cross-bridged cyclam chelator.

Early detection of cutaneous melanoma is essential, as prognosis with metastatic melanoma is poor. Previous studies showed that (64)Cu-DOTA-ReCCMSH(Arg(11)) (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid), a cyclic analog of alpha-melanocyte-stimulating hormone (alpha-MSH), has the potential for the detection of malignant melanoma using PET. However, (64)Cu-DOTA-ReCCMSH(Arg(11)) demonstrated high background in nontarget tissues due to the in vivo instability of the Cu-DOTA moiety. CBTE2A (CBTE2A is 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) has been shown to be a more stable copper chelate with improved in vivo stability, resulting in an improvement in clearance from nontarget tissues. The goal of this study was to conjugate CBTE2A to the alpha-MSH targeting ReCCMSH(Arg(11)) peptide for labeling to (64)Cu and to investigate whether the increased metal-chelate stability with CBTE2A would improve imaging quality. METHODS: The recyclized peptide CBTE2A-ReCCMSH(Arg(11)) was synthesized using a solid-phase peptide synthesizer followed by rhenium cyclization. In vivo characteristics of (64)Cu-CBTE2A-ReCCMSH(Arg(11)) were examined with small-animal PET and acute biodistribution studies in B16/F1 tumor-bearing mice. RESULTS: Biodistribution studies showed high and rapid receptor-mediated tumor uptake with values similar to those reported for (64)Cu- and (86)Y-labeled DOTA-ReCCMSH(Arg(11)). Nontarget organ concentration for (64)Cu-CBTE2A-ReCCMSH(Arg(11)) was considerably lower than that of the (64)Cu-DOTA analog, resulting in significantly higher tumor-to-nontarget tissue ratios. Compared with (86)Y-DOTA-ReCCMSH(Arg(11)), (64)Cu-CBTE2A-ReCCMSH(Arg(11)) demonstrated increased tumor retention and kidney clearance. Small-animal PET images showed that the tumor could be clearly visualized at all time points (0.5-24 h). CONCLUSION: Our data suggest the superior stability of the (64)Cu-CBTE2A moiety compared with (64)Cu-DOTA, making (64)Cu-CBTE2A-ReCCMSH(Arg(11)) an ideal candidate for the PET of malignant melanoma.     

Oral health of the methamphetamine abuser.

PURPOSE: The pharmacology of methamphetamine is reviewed, and the effects of methamphetamine use on oral health are described. SUMMARY: Methamphetamine is a highly addictive amphetamine analogue, initially synthesized in 1919. Illicit methamphetamine use leads to devastating effects on health, particularly the dentition. Illegal production of methamphetamine has skyrocketed in recent years, as have the number of users. The chief complaint of methamphetamine users is xerostomia. Without the protective effects of saliva, caries development in these patients is rampant. The typical pattern of decay involves the facial and cervical areas of both the maxillary and mandibular teeth, with eventual progression to frank coronal involvement. The acidic substances used to manufacture this drug have also been implicated as a cause of tooth decay and wear in users, as has bruxism as a result of drug-induced hyperactivity. When possible, these patients should be referred to a dentist to improve their oral health status and minimize the potential for adverse cardiovascular sequelae. Other preventive measures for methamphetamine users include stimulating saliva flow and increasing fluoride supplementation. Pharmacists should also counsel users to avoid carbohydrate-rich soft drinks in favor of water. Oral moisturizers may also be effective. CONCLUSION: Methamphetamine use causes xerostomia secondary to sympathetic central nervous system activation, rampant caries caused by high-sugar intake in the absence of protective saliva, and bruxism as a result of hyperactivity. Practitioners should know how to recognize the signs of and manage the oral health of patients with a history of methamphetamine use.     

Assessing the Stiffness of Spinal Fusion in Animal Models

The clinical goal of spinal fusion is to reduce motion and the associated pain. Therefore, measuring motion under loading is critical. The purpose of this study was to validate four-point bending as a means to mechanically evaluate simulated fusions in dog and rabbit spines. We hypothesized that this method would be more sensitive than manual palpation and would be able to distinguish unilateral vs bilateral fusion. Spines from four mixed breed dogs and four New Zealand white rabbits were used to simulate posterolateral fusion with polymethyl methacrylate as the fusion mass. We performed manual palpation and nondestructive mechanical testing in four-point bending in four planes of motion: flexion, extension, and right and left bending. This testing protocol was used for each specimen in three fusion modes: intact, unilateral, and bilateral fusion. Under manual palpation, all intact spines were rated as not fused, and all unilateral and bilateral simulated fusions were rated as fused. In four-point bending, dog spines were significantly stiffer after unilateral fusion compared with intact in all directions. Additionally, rabbit spines were stiffer in flexion and left bending after unilateral fusion. All specimens exhibited significant differences between intact and bilateral fusion except the rabbit in extension. For unilateral vs bilateral fusion, significant differences were present for right bending in the dog model and for flexion in the rabbit. Unilateral fusion can provide enough stability to constitute a fused grade by manual palpation but may not provide structural stiffness comparable to bilateral fusion.     

Frozen section analysis of esophageal endoscopic mucosal resection specimens in the real-time management of Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the validity of frozen section analysis of endoscopic mucosal resection (EMR) specimens from Barrett's esophagus as compared with permanent sections for the detection of neoplasia. Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions. METHODS: EMR specimens from Barrett's esophagus with high-grade dysplasia (HGD) and/or carcinoma were tested by frozen section. Pathologists evaluated EMR specimens for the depth of invasion as well as the appearance of clear margins of resection. The kappa statistic was calculated to assess the degree of agreement between the frozen section and permanent section diagnoses. RESULTS: Twenty-three consecutive patients underwent 30 EMRs with frozen section diagnosis. Frozen section revealed a carcinoma in 7 specimens (23%) and dysplasia in 20 (66%). Permanent sections found carcinoma in 8 specimens (26%), dysplasia in 19 specimens (63%), and normal or nondysplastic Barrett's esophagus in the remainder. The kappa statistic for the depth of invasion of EMR specimens was 0.93 (near perfect agreement). The kappa statistic for the margins of the EMR specimens was 0.80 (excellent agreement). CONCLUSIONS: This study indicated that frozen section analysis of esophageal EMR specimens is valid as compared with permanent section. This technique might allow rapid evaluation about the degree and depth of involvement of cancers. This allows physicians to make decisions regarding further therapy if margins are involved or decrease the use of EMR for histologically benign-appearing lesions.