Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies.

PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed primary brain tumors for the presence of hypoxia, as indicated by the uptake of 18F-fluoromisonidazole (18F-FMISO) and to examine the relationship of hypoxia to the uptake of 18F-FDG and molecular markers of hypoxia. METHODS: Seventeen patients with suspected primary glioma were enrolled prospectively in this study. Sixteen patients had histology, with 2 having metastatic disease. All patients had PET studies with 18F-FMISO and 18F-FDG and MRI studies. Immunohistochemistry was undertaken with tumor markers of angiogenesis and hypoxia. Patients were monitored for disease progression and statistical analysis of data was performed. RESULTS: Of the 14 patients with histology, 8 died with a median time of 16 mo (range, 2-30 mo) until death. Of those who died, 7 had positive and 1 had negative 18F-FMISO uptake. 18F-FMISO uptake was observed in all high-grade gliomas but not in low-grade gliomas. A significant relationship was found between 18F-FDG or 18F-FMISO uptake and expression of VEGF-R1 and Ki67 expression. Other immunohistochemical markers demonstrated a trend toward increased uptake but none was significant. CONCLUSION: 18F-FMISO PET provides a noninvasive assessment of hypoxia in glioma and was prognostic for treatment outcomes in the majority of patients. 18F-FMISO PET may have a role not only in directing patients toward targeted hypoxic therapies but also in monitoring response to such therapies.     

Atypical brown fat distribution in young males demonstrated on PET/CT

The development of PET/CT has led to the recognition that metabolically active fat, referred to as "brown fat," can accumulate FDG and represents a possible source of false-positive scans in oncology patients. Numerous reports have described the typical appearance of brown fat, which most commonly presents as neck and paravertebral uptake in young female patients. Other described sites of uptake include the mediastinum and retroperitoneum. We present examples of 2 cases of atypical diffuse brown fat uptake seen in the subcutaneous fat of the thighs, abdomen, and pelvis. Both of these patients were young men and did not show uptake in the typical supraclavicular and neck fat. Although rare in our experience, knowledge of this condition may prevent misinterpretation of this finding as an infiltrative condition of the skin, such as lymphoma.     

Effects of a synthetic retinoid on skin structure, matrix metalloproteinases, and procollagen in healthy and high-risk subjects with diabetes

Background

In diabetes, foot ulceration may result from increased skin fragility. Retinoids can reverse some diabetes-induced deficits of skin structure and function, but their clinical utility is limited by skin irritation. The effects of diabetes and MDI 301, a nonirritating synthetic retinoid, and retinoic acid have been evaluated on matrix metalloproteinases (MMPs), procollagen expression, and skin structure in skin biopsies from nondiabetic volunteers and diabetic subjects at risk of foot ulceration using organ culture techniques.

Methods

Zymography and enzyme-linked immunosorbent assay were utilized for analysis of MMP-1, -2, and -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) and immunohistochemistry for type I procollagen protein abundance. Collagen structure parameters were assessed in formalin-fixed, paraffin-embedded tissue sections.

Results

The % of active MMP-1 and -9 was higher and TIMP-1 abundance was lower in subjects with diabetes. Type 1 procollagen abundance was reduced and skin structural deficits were increased in diabetes. Three μM MDI 301 reduced active MMP-1 and -9 abundance by 29% (P<.05) and 40% (P<.05), respectively, and increased TIMP-1 by 45% (P=.07). MDI 301 increased type 1 procollagen abundance by 40% (P<.01) and completely corrected structural deficit scores. Two μM retinoic acid reduced MMP-1 but did not significantly affect skin structure.

Conclusions

These data indicate that diabetic patients at risk of foot ulceration have deficits of skin structure and function. MDI 301 offers potential for repairing this skin damage complicating diabetes.     

177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide

Purpose  

The aim of this retrospective study was to determine whether patients with previous peptide receptor radionuclide therapy using high-activity ¹¹¹In-pentetreotide can be safely treated with ¹⁷⁷Lu-octreotate and whether addition of radiosensitising chemotherapy increases the toxicity of this agent.     

Cutaneous structural and biochemical correlates of foot complications in high-risk diabetes

OBJECTIVE Impairment of skin quality may contribute to diabetic foot ulceration (DFU). Our goal was to determine whether high-risk patients exhibited specific skin structural and metabolic deficits that could predispose to foot complications. RESEARCH DESIGN AND METHODS A total of 46 patients comprising 9 diabetic control subjects, 16 with diabetic peripheral neuropathy (DPN) alone, and 21 with recurrent DFUs (including 9 with Charcot neuroarthropathy [CNA]) were recruited and compared with 14 nondiabetic control (NDC) subjects. DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Skin punch biopsies (3 mm) were performed on upper and lower leg skin for measurements of intraepidermal nerve fiber density (IENFD), structural analysis, type 1 procollagen abundance, tissue degrading matrix metalloproteinases (MMPs), and poly(ADP-ribose) (PAR) immunoreactivity. RESULTS MNSI scores were comparable across DPN groups. IENFD was decreased by diabetes and DPN but did not differ between neuropathic groups. Skin structural deficit scores were elevated in all neuropathic subjects, particularly in the DFU group. Type 1 procollagen abundance was reduced in DFU subjects 387 ± 256 units (mean ± 1 SD) compared with NDC subjects (715 ± 100, P < 0.001). MMP-1 and MMP-2 were activated by diabetes. PAR immunoreactivity was increased in DFU (particularly in the CNA group; P < 0.01) compared with other DPN subjects. CONCLUSIONS Increased PAR, reduced type 1 procollagen abundance, and impaired skin structure are associated with foot complications in diabetes. The potential of therapies that improve skin quality to reduce DFU needs to be investigated.     

18F-FDG PET/CT显像在鼻咽癌分期与疗效监测中的临床应用价值

背景与目的:18F-脱氧葡萄糖(fluorine-18 fluorodeoxyglucose,18F-FDG)PET/CT显像可明显提高肺癌、食管癌等多种肿瘤的诊断、分期与疗效监测的准确性,有助于更准确地制定治疗方案.本研究探讨全身18F-FDG PET/CT显像在鼻咽癌首次分期、再分期及疗效监测中的临床应用价值.方法:回顾性分析澳大利亚Peter MacCallum肿瘤中心2002年2月至2005年12月43例鼻咽癌患者的18F-FDG PET/CT全身扫描报告,根据临床资料、病理结果及临床随访结果,计算18F-FDG PET/CT与传统影像学检查CT、MRI的准确性、特异性、灵敏度、阳性预测值与阴性预测值,并对结果进行比较和分析.结果:18F-FDGPET/CT诊断鼻咽癌总的准确率、敏感性、特异性、阳性预测值与阴性预测值分别为95.3%、100.0%、85.7%、93.8%、100.0%,传统影像学检查CT、MRI分别为65.5%、79.4%、64.7%、81.8%、57.9%. 18F-FDG PET/CT诊断结果使2例首次分期、7例再分期患者治疗方案得到改变,并影响1例首次分期和3例再分期患者治疗方案的制定;在疗效监测组中,指导医生修改治疗方案共11例(其中5例为原则性的修改).18F-FDG PET/CT检测到2例第二原发肿瘤,1例是甲状腺癌,1例是低度恶性胃癌.结论:18F-FDG PET/CT全身显像对鼻咽癌N、M分期与疗效监测的临床作用可能优于CT、MR检查.     

18F-FDG PET/CT发现肿瘤患者意外病灶的临床价值

目的评价^18F-脱氧葡萄糖（FDG）PET／CT全身显像探测肿瘤患者意外病灶的临床价值。方法回顾性分析澳大利亚Peter MaeCallum肿瘤医院PET／CT中心2002年8月～2003年7月1727例肿瘤患者^18F—FDGPET／CT全身显像报告，男980例，女747例，中位年龄63岁，随访37个月（中位时间为27．5个月）。意外病灶指新发现的与原发肿瘤无关的良性病灶或第2原发肿瘤。通过分析病历记录、病理结果、其他影像学检查结果及临床随访，确定病灶最终结果。结果1727例患者共发现238例（13．8％）有意外病灶，其中213例220个意外病灶具有完整的随访资料。60个病灶怀疑为意外第2原发肿瘤，其中21．7％（13／60）证实为真阳性，70．0％（42／60）为假阳性，8．3％（5／60）至研究结束时未得到证实。38个甲状腺意外良性病灶，其中9个被证实为临床前恶性或恶性病灶，26个良性，3个未能证实。38个纵隔意外良性病灶，其中86．8％（33／38）证实为良性，7．9％（3／38）为原发肿瘤淋巴结侵犯，5．3％（2／38）未能证实其性质。其他部位84个意外良眭病灶，94．0％（79／84）证实为真阴性，6．0％（5／84）未能证实。共22例患者被证实存在第2原发肿瘤病灶，占本研究总人群的1．3％。结论^18F—FDGPET／CT全身显像是目前探测肿瘤患者意外病灶较好的无创方法，为制定临床治疗方案提供及时准确的依据。     

177Lu-octreotate治疗神经内分泌胃肠胰腺肿瘤的SPECT显像研究

目前对于转移性神经内分泌胃肠胰腺肿瘤（NET）没有很好的治疗方法。分化良好的神经内分泌肿瘤多过度表达生长抑素受体（SSTR），尤其是亚型SSTR2。人工合成生长抑素衍生物如奥曲肽（octreotide）能治疗激素过度表达的症状，而采用放射性核素标记octreotide及其衍生物对NET进行靶向治疗效果更好，称为肽类受体介导的放射性核素治疗（PRRT），早期主要应用^111In-octreotide，     

Clinical experience with the first combined positron emission tomography/computed tomography scanner in Australia

Metabolic imaging with fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is increasing rapidly worldwide because of superior accuracy compared with conventional non-invasive techniques used for evaluating cancer. Limited anatomical information from FDG-PET images alone dictates that complementary use with structural imaging is required to optimise benefit. Recently, combined positron emission tomography/computed tomography (PET/CT) scanners have overtaken standalone PET scanners as the most commonly purchased PET devices. We describe our experience of over 5500 scans performed since the first PET/CT scanner in Australia was commissioned at the Peter MacCallum Cancer Centre (PMCC), Melbourne, in January 2002. Clinical indications for PET/CT scans performed at PMCC largely reflect current Medicare reimbursement policy. Advantages of PET/CT include greater patient comfort and higher throughput, greater diagnostic certainty and accuracy, improved biopsy methods, and better treatment planning. We believe PET/CT will underpin more effective and efficient imaging paradigms for many common tumours, and lead to a decrease in imaging costs.