The a v b 3 integrin plays a pivotal role in angiogenesis and tumor metastasis. Angiogenic blood vessels overexpress a v b 3 integrin, as in tumor neovascularization, and a v b 3 integrin expression in other microvascular beds and organs is limited. Therefore, a v b 3 integrin is a suitable receptor for tumor-targeting imaging and therapy. Recently, tetrameric and dimeric RGD peptides have been developed to enhance specificity to a v b 3 integrin. In comparison to the corresponding monomeric peptide, however, these peptides show high levels of accumulation in kidney and liver. The purpose of this study is to evaluate tumor-targeting properties and the therapeutic potential of 111 In-and 90 Y-labeled monomeric RGD peptides in BALB/c nude mice with SKOV-3 human ovarian carcinoma tumors. DOTA-c(RGDfK) was labeled with 111 In or 90 Y and purified by HPLC. A biodistribution study and scintigraphic images revealed the specific uptake to a v b 3 integrin and the rapid clearance from normal tissues. These peptides were renally excreted. At 10 min after injection of tracers, 111 In-DOTA-c(RGDfK) and 90 Y-DOTA-c(RGDfK) showed high uptake in tumors (7.3 6 0.6% ID/g and 4.6 6 0.8% ID/g, respectively) and gradually decreased over time (2.3 6 0.4% ID/g and 1.5 6 0.5% ID/g at 24 hr, respectively). High tumor-to-blood and -muscle ratios were obtained from these peptides. In radionuclide therapeutic study, multipledose administration of 90 Y-DOTA-c(RGDfK) (3 3 11.1 MBq) suppressed tumor growth in comparison to the control group and a single-dose administration ( The a v b 3 integrin recognizes the amino acid sequence of arginine-glycine-aspartic acid (RGD peptide). On the basis of the RGD peptide, many peptidomimetic compounds and peptides have been designed to antagonize the a v b 3 integrin. 4 These compounds and anti-a v b 3 integrin monoclonal antibodies have been reported to inhibit angiogenesis without affecting preexisting vessels. 2,5,6 Because of its restricted expression, the a v b 3 integrin is an attractive targeting molecule for tumor imaging and therapy, leading to decreased side effects compared to conventional chemotherapy.The expression of the a v b 3 integrin has been reported to be associated with metastatic potential in melanoma, breast cancer, and colon cancer. 7-9 The development of radiopharmaceuticals for targeting the a v b 3 integrin would be clinically beneficial, not only for screening and for treating patients with a v b 3 integrin-positive tumors but also for monitoring therapeutic efficacy.Many RGD peptides labeled with gamma-emitting and positron-emitting nuclides ( 18 F, 64 Cu, 99m Tc, 125 I, etc.) have been reported as angiogenesis-imaging agents. 10 A recent trend in the development of RGD peptides is the multimerization of RGD peptides to improve the high tumor accumulation and retention of RGD peptides. 11 However, this also leads to the enhancement of radioactive accumulation in nontargeted organs such as kidney and liver. 12 Compared with antibody or multimeric RGD peptides, monomeric RGD ...

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PurposeThe aim of this study was to assess whether migration of thallium-201 (201Tl) to the olfactory bulb were reduced in patients with olfactory impairments in comparison to healthy volunteers after nasal administration of 201Tl.Procedures10 healthy volunteers and 21 patients enrolled in the study (19 males and 12 females; 26–71 years old). The causes of olfactory dysfunction in the patients were head trauma (n = 7), upper respiratory tract infection (n = 7), and chronic rhinosinusitis (n = 7). 201TlCl was administered unilaterally to the olfactory cleft, and SPECT-CT was conducted 24 h later. Separate MRI images were merged with the SPECT images. 201Tl olfactory migration was also correlated with the volume of the olfactory bulb determined from MRI images, as well as with odor recognition thresholds measured by using T&T olfactometry.ResultsNasal 201Tl migration to the olfactory bulb was significantly lower in the olfactory-impaired patients than in healthy volunteers. The migration of 201Tl to the olfactory bulb was significantly correlated with odor recognition thresholds obtained with T&T olfactometry and correlated with the volume of the olfactory bulb determined from MRI images when all subjects were included.ConclusionsAssessment of the 201Tl migration to the olfactory bulb was the new method for the evaluation of the olfactory nerve connectivity in patients with impaired olfaction.