Carcinoma of unknown primary (CUP) is a diagnostic and therapeutic challenge in oncology.The early and correct detection of the primary tumors of CUP is very important to its diagnosis, treatment, therapeutic response evaluation and prognosis prediction.This review summarizes the implications and development of the imaging technologies, especially 18F-FDG PET/CT scan, in the diagnosis, treatment and prognosis prediction of CUP patients.

The nanobody is a novel antibody fragment,which has beneficial biophysical and pharmacokinetic properties,such as the small molecular weight,high affinity and specificity for antigen.Nanobody is ideally suitable for molecular imaging as a targeting probe that could label antigen at nmol level in vitro.In animal models of xenografted tumor,atherosclerotic plaques and brain disorders,the target tissues were specifically and clearly detected and the high tumor-to-blood (T/B) ratios were obtained.Structural or chemical modified nanobodies will have higher affinity and retention to target tissues,and be convenient for the application of molecular imaging.With the development of the related research,nanobody-based molecular imaging will be gradually transformed into the clinical applications,and play an important role in early diagnosis and therapeutic assessment.

Early diagnosis and accurate staging are important for planning therapeutic intervention to improve outcomes in patients with malignant melanoma (MM).Noninvasive molecular imaging has been extensively studied in cancer diagnosis,staging,therapeutic evaluation,and prognosis.Several radiopharmaceuticals have been developed to diagnose and treat MM,such as monoclonal antibodies,melanocortin receptors,benzamide (BZA) and BZA analogs.In this review,the characteristics and limitations of these radionuclide molecular probes are summarized and discussed.

To study the changes in every part of the beta-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups: IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1+, 2+, 3+ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the beta-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group (P < 0.001), while the enzymes were significantly higher in I/R (P < 0.001). The Bmax of beta-AR in IP was much higher than that in I/R (P < 0. 001), but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R (P < 0.05, 0.002 and 0.001, respectively). In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of beta-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA.
Ischemic Preconditioning, Myocardial ; Myocardium/*metabolism ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta/*physiology ; Signal Transduction

Optical imaging is one of the molecular imaging modalities,and it consists of three imaging methods (fluorescence,bioluminescence and diffusion imaging).For fluorescence imaging,quantum dots (QDs) are inorganic semiconductor nanocrystals with a diameter from 2 to 100 nm.Compared with organic fluorescent dye,QDs have several unique optical properties,such as wide and continuous excitation spectra,narrow and symmetrical emission spectrum,strong fluorescence intensity and high resistance to photobleaching.This article reviews the optical properties of QDs and their development in the field of molecular imaging from in vitro and in vivo applications,as well as the limitations and problems.

Early detection and accurate evaluation of vulnerable plaques is important to clinical prevention and in time intervention of atherosclerosis plaque rupture,which is the main reason of cardiovascular and cerebrovascular emergency events.Molecular imaging reveals the formation and progression mechanisms of atherosclerosis at the molecular level,and thus has obvious superiority in early detection and evaluation of vulnerable plaques.Suitable targets are the major contents of molecular probe research.Probes of different imaging modalities have been used to detect vulnerable plaques.The targets including low density lipoprotein,macrophage,adhesion molecule,micro calcification,activated protease,apoptosis,proliferation gene,integrin and thrombus.The mechanism of detecting different targets is different,and the effectiveness varies as well.This review summarizes the development of imaging probes for molecular detection of atherosclerosis vulnerable plaques.

Fibroblast activation protein (FAP) is a marker protein of cancer-associated fibroblasts(CAFs). It is highly expressed in more than 90% of epithelial cancers and hardly expressed in normal tissues. Therefore, FAP is a very promising target. Radionuclide labeled FAP targeted molecular probes can be used for PET or SPECT imaging. In particular, 68Ga-FAP inhibitors (FAPIs) PET/CT has shown good prospects in the clinic, providing a new idea for early diagnosis, accurate staging and radionuclide treatment of tumors. In addition, FAP is also highly expressed in certain non-tumor diseases, especially those related to fibrosis. In this article, the research progress of radionuclide-labeled FAP targeted molecular probes is reviewed.

Objective To evaluate the application value of 18 F‐FDG PET/CT in patients with fever of unknown origin (FUO) to improve the etiological diagnosis accuracy of PET/CT in patients with FUO and provide better service for clinical prac‐tice .Methods Clinical data and imaging results of 144 cases of FUO patients diagnosed through 18 F‐FDG PET/CT examination in Wuhan union hospital from December 2009 to December 2011 were retrospectively analyzed .The final diagnoses were based on sur‐gical pathology ,aspiration cytology ,or discharge diagnosis combined with more than 12 months of follow‐up results .All the PET/CT images were analyzed and the clinical application value of PET/CT in FUO patients were evaluated through the diagnose rate , diagnose efficiency and clinical staging of malignant tumor .Results Among the 144 patients ,there were 130 cases ultimately had clear diagnosis ,which including 41 cases of malignant tumor ,89 cases of benign lesions and 14 cases the cause of unknown .PET/CT detected abnormal lesions for 97 .6% (40/41) of patients with malignant lesions and 88 .7% (79/89) of patients with benign le‐sions ,and the diagnostic sensitivity ,specificity ,accuracy ,positive predictive value ,and negative predictive value were :97 .6% (40/41) ,86 .5% (77/89) ,90% (117/130) ,76 .9% (40/52) and 98 .7% (77/78) .PET/CT detected the primary lesions for the first time in 46 .3% (19/41) patients with malignant tumor ,and detected more lesions than the traditional imaging methods in 92 .7% (38/41) of these patients .Conclusion 18 F‐FDG PET/CT imaging can provided important reference value for the detection of primary lesions ,the qualitative diagnosis of benign and malignant lesions and clinical staging of malignant lesions .

The validity of (99m)Tc-YIGSR, a novel receptor radio-tracer, in imaging the Ehrlich ascites tumor was evaluated. YIGSR, a pentapeptide of laminin, was labeled with (99m)Tc by using a bifunctional chelator S-Acetly-NH(3)-MAG(3). The MIBI was labeled with (99m)Tc by following the kit instruction. The mice of tumor group were intravenously injected 1-2 mCi of (99m)Tc-YIGSR or (99m)Tc-MIBI via caudal vein, immobilized and imaged under a Gamma camera. The same procedure was performed in mice of blockade group, in which the unlabeled YIGSR was previously injected to block the receptor-recognition sites, and inflammation group serving as control. The reverse-phase Sep-Pak C(18) chromatogram was found to have an essentially complete conjugation between YIGSR and S-Acetly-NH(3)-MAG(3). The conjugated YIGSR could be radio-labeled successfully with (99m)Tc at room temperature and neutral pH, with a radio-labeling yield of 62%. Without the chelator S-Acetly-NH(3)-MAG(3), the YIGSR was labeled with (99m)Tc at an efficiency of 4%. The imagological study revealed obvious tumor accumulation of (99m)Tc-YIGSR 15 min after the injection, and the uptake peaked after 3 h with a tumor-to-muscle ratio (T/M) of 11.36. The radio-tracer was slowly cleared up and resulted in a T/M of 3.01 at the 8th h after the injection. As for blocked group, the tumor uptake of radiotracer was significantly lower, with the highest T/M being 4.61 after 3 h and 0.89 after 8 h. The T/M was 3.72 at the 3rd h and 1.29 at the 8th h after the (99m)Tc-YIGSR injection in the inflammatory group. The T/M was significantly higher in tumor group than in inflammatory group or control group (P<0.001). In the 99mTc-MIBI group, the T/M was 1.40 at the 3rd h and 0.55 at the 8th h after the injection, which showed a significant difference as compared with (99m)Tc-YIGSR (P<0.001). It is concluded that YIGSR can be successfully radiolabelled by using S-Acetly-NH(3)-MAG(3). (99m)Tc-YIGSR has many advantages in tumor imaging, such as quick and clear visualization, high sensitivity and specificity, and satisfactory target/non-target ratio (N/NT). It promises to be tumor radio-tracer.
Carcinoma, Ehrlich Tumor/*radionuclide imaging ; Radioactive Tracers ; Radiopharmaceuticals/*diagnostic use ; Receptors, Laminin/*metabolism ; Technetium Tc 99m Mertiatide/*diagnostic use ; Technetium Tc 99m Sestamibi/*diagnostic use

To investigate a new kind of tumor tracer 99mTc-YIGSR developed from a five amino structure (YIGSR) of the Laminin -chain, which can bind to the laminin receptors of tumor specifically, and radiolabeled with MAG3. (1) Preparation of the 99mTc-YIGSR probe: with S-Acetly-NH3-MAG3 as the chelator and with proper reductants YIGSR was labeled with 99mTc; (2) Cell culture and viability measurement: EAC was maintained in RPMI 1640 supplemented with calf serum; the trypan blue exclusion was applied to calculate the cell viability; (3) Study of the cell dynamic: The EAC's uptake of 99mTc-YIGSR and 99mTc-MIBI was observed at 37 degrees C and 22 degrees C, respectively. (1) The labeling efficiencies of 99mTc-YIGSR and 99mTc-MIBI were (62 +/- 3)% and (96 +/- 2)%, respectively; (2) The cell viability was declined with time of incubation; (3) At 37 degrees C, the EAC'S uptake of 99mTc-YIGSR and 99mTc-MIBI reached the peak of (43.16 +/- 2.4) % and (24.4 +/- 1.8) % at 60 min, respectively; and at 22 degrees C, the highest uptake was (26.5 +/- 2.1) % and (9.47 +/- 1.9) % at 60 min, respectively. The in vitro study suggests that 99mTc-YIGSR is superior to 99mTc-MIBI in cell uptake and has potential value in tumor imaging.
Carcinoma, Ehrlich Tumor/*radionuclide imaging ; Laminin ; Oligopeptides ; Radiopharmaceuticals/diagnostic use ; Radiopharmaceuticals/*pharmacokinetics ; Technetium Tc 99m Mertiatide/diagnostic use ; Technetium Tc 99m Mertiatide/*pharmacokinetics ; Technetium Tc 99m Sestamibi/diagnostic use ; Technetium Tc 99m Sestamibi/*pharmacokinetics ; Tissue Distribution