In memory of Rainer RudolphBreast cancer is still one of the most frequently occurring tumors in women. Severe and often therapy-limiting side effects are a major obstacle in chemotherapy. New delivery concepts that reduce systemic side effects are needed to optimize anticancer therapies, and selective targeting concepts are required for early and selective tumor diagnosis. Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is a C-terminal amidated peptide hormone consisting of 36 amino acid residues.[1, 2] NPY-mediated functions are transmitted by so-called Y receptors, named Y 1 , Y 2 , and Y 5 receptors, which bind NPY with nanomolar affinity. All Y receptors are members of the class A of heptahelix receptors, that signal through heterotrimeric G proteins. [3,4] Reubi et al. have recently described Y-receptor expression in human breast cancer. They have shown that over 90 % of all breast tumors and 100 % of the examined metastases express Y 1 receptors.[5] Interestingly, a shift of the receptor subtype from Y 2 receptors in healthy tissue to Y 1 receptors during neoplasm was found, which is potentially related to reduced differentiation. Based on NPY and the known structure-activity relationships for Y 1 -receptor binding, [6] we designed, synthesized, and characterized two analogues for tumor labeling that vary in the position of the chelator to conjugate 99m Tc. Peptides 1 a and 2 a were synthesized with a N a -histidinyl acetyl (N a His-ac) chelator [7] at the N terminus, whereas peptides 1 b and 2 b were modified at the N e side chain of Lys 4 . The tridentate ligand N a His-ac is able to form stable and biologically active complexes. [8,9] Modification of the resin-bound peptide was performed by an efficient strategy (Scheme 1). In the first step, bromoacetic acid was activated by diisopropylcarbodiimide to form the corresponding anhydride. His(Trt)-OtBu was then added and the NHÀ CH bond was formed by HBr elimination. Cleavage of the peptide yielded His-acetyl peptides either at the N terminus or at the N e side chain of Lys 4 . Rhenium was used as a cold surrogate for 99m Tc and introduced for in vitro studies
Objectives: To evaluate the role of iodine-131 metoiodobenzylguanidine (iodine-131 MIBG) scanning in the management of paediatric patients with neuroblastoma. Subjects and Methods: Forty-three iodine-131 MIBG scans were performed on 26 children, 18 male and 8 female, ranging in age from 8 months to 11 years. Bone scan, computed tomography (CT) images and findings of bone marrow biopsy were compared with the iodine-131 MIBG scan findings. Results: Of the 26 patients, 18 (69%) showed abnormal iodine-131 MIBG avidity and were proven to have a neural crest tumour on histology. The remaining 8 (31%) patients had normal iodine-131 MIBG scans, and histology showed a malignancy other than a neural crest tumour. Iodine-131 MIBG scans showed the primary site in 16 of 17 patients while CT showed 14 primary sites. In follow-up studies, the results were as follows: iodine-131 MIBG showed no evidence of disease in 4 compared with 3 on CT, persistent disease in 2 on iodine-131 MIBG and 4 on CT; recurrence in 1 on iodine-131 MIBG and 0 on CT; MIBG scans detected double the number of bony lesions compared with bone scans. The findings on iodine-131 MIBG scans and bone marrow biopsy were in agreement in 16/18 cases. Patients in whom iodine-131 MIBG scans showed disease resolution had better clinical outcomes. Conclusion: The findings indicate that iodine-131 MIBG scanning is useful for the diagnosis, staging, evaluation of response to therapy and detection of recurrences in patients with neuroblastoma. It exhibited a clear advantage over CT in detecting the primary site and soft issue metastases and was also superior to bone scanning in detecting skeletal metastases. It also reliably demonstrated bone marrow involvement.
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