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Uptake of indium-111 in bone marrow is seen in patients who have received 111In-labelled antibody. We report a case in which 111In uptake was not seen in the area of previous irradiation whereas fairly high uptake was noted in other bone marrow areas. 111In-labelled monoclonal antibody, which reacts with mucin, was injected into a patient with cancer of the sigmoid colon who had received radiotherapy for uterine cervical cancer 5 years previously. Marked accumulation of the antibody was observed in the tumour. Uptake of 111In in bone marrow was also seen except in the previously irradiated pelvic region. This phenomenon supports the idea that bone marrow uptake of 111In is the result of transchelation of 111In from antibody to transferrin.

Scintigraphy using gallium-67 (67Ga) citrate and penvaralent technetium-99m dimercaptosuccinic acid ([99mTc(V)]DMSA) and other radiological examinations were performed in three patients with solitary muscular sarcoidosis who had tumor-like muscular lesions. Although distinction from other invasive soft tissue tumors was difficult using plain and enhanced computed tomography and magnetic resonance imaging, marked uptake of 67Ga and moderate uptake of [99mTc(V)]DMSA were shown at the sites of granulomatous inflammatory lesions of sarcoidosis. Both 67Ga and [99mTc(V)]DMSA scintigraphy could be of value in the diagnosis and detection of distribution of granulomas of sarcoidosis in the soft tissue and in determining the appropriate region for biopsy.

131I-metaiodobenzylguanidine (MIBG) therapy was given to five patients with malignant pheochromocytoma. The patients received 1-3 doses of 3.33-4.625 GBq (total dose: 3.7 to 10.73 GBq). Partial tumor regression was observed in two patients, the tumor was unchanged in two patients, and slow progression was noted in one patient. Marked improvement in clinical symptoms was achieved in four patients. The other patient had no symptoms before 131I-MIBG treatment, but the serum epinephrine and dopamine decreased. There were no severe untoward responses in four patients. However, one patient developed transient but severe orthostatic hypotension, hypertension, and hyperglycemia from 1 week to 1 month after 131I-MIBG administration. Although complete remission was not obtained, all the patients achieved some benefit from 131I-MIBG therapy. Thus, 131I-MIBG appears to be useful for the palliation of malignant pheochromocytoma.

The new immunoradiometric assay for CA125 (CA125II assay) uses the monoclonal antibody M11 as an immunoadsorbent. The epitope recognized by M11 is different from the OC125 epitope. Monoclonal antibodies 130-22 and 145-9 recognize an epitope designated as CA130 on the molecule expressing the OC125 epitope. Similarity of M11 epitope to the epitope of anti-CA130 antibodies and dissociation of antigen levels measured by the original CA125 assay and new CA125II assay were examined. Anti-CA130 antibodies partially competed with M11 for the M11 epitope. Among more than 20,000 serum samples we found 12 patients in whom the serum CA125 concentration measured by the CA125II assay was different from that measured by the original assay. In 11 out of 12 patients the CA125 concentration was moderately or extremely high by the original assay but very low by the CA125II assay. Eight of the 11 patients had benign disease, one had no apparent disease and two had cancer. The antigen level determined by CA130 assay was very low in all the 11 patients. In one patient the CA125II assay showed a higher antigen level than the original assay or CA130 assay. The heterogeneity of the epitope expression could cause the dissociation of CA125 levels measured by the different monoclonal antibodies.

The authors report marked accumulatlon of pentavalent technetium-99m dimercaptosuccinic acid in metastatic tumors from a renal cell carcinoma in the brain and the scalp on brain SPECT images

To assess the potential of technetium-99m (V) dimercaptosuccinic acid (DMSA) scintigraphy for diagnosis of soft-tissue tumors.Tc-99m (V) DMSA scintigraphy was performed in 76 patients with histologic proof of soft-tissue tumors. In 57 of these patients, gallium-67 citrate scintigraphy was performed within 2 weeks after Tc-99m (V) DMSA scintigraphy.Uptake of Tc-99m (V) DMSA was clearly detected in almost all sarcomas, metastatic carcinomas, highly recurrent benign tumors (ie, extra-abdominal desmoids and tenosynovial giant cell tumors), superficial and deep hemangiomas, and granulomatous soft-tissue lesions but was not found in other benign solid tumors of soft tissue. Uptake of Ga-67 citrate was clearly detected in all inflammatory lesions and metastatic carcinomas, eight of 14 sarcomas (57%), and two of 10 highly recurrent benign tumors (20%) but was not found in hemangiomas or benign soft-tissue tumors.Low-grade malignant and highly recurrent benign lesions, which often recur after surgery, were detected more accurately with Tc-99m (V) DMSA scintigraphy than with Ga-67 citrate scintigraphy.

BACKGROUND & AIM: The diagnosis of colitis associated cancer (CAC) remains difficult despite technologic improvements in modern endoscopes. It can be challenging to see a tumor against a background of inflammation. Recently, we demonstrated that ovarian cancer peritoneal implants can be easily visualized In Vivo using a fast reacting gamma-glutamyltransferase (GGT) activatable optical probe, which only fluoresces in the presence of GGT activity. The aim of this study was to test this agent in the context of a colitis associated carcinogenesis model. METHODS: Expression of GGT in colon cancer cell lines was examined with the GGT activatable probe (1 μM) using a fluorescencemicroscopy and a flow cytometry. A mouse model of CAC induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) was then used for the In Vivo experiment. The distal colon up to the splenic flexure was examined with conventional white light and fluorescence micro-colonoscopy before and after intrarectal administration (50 μM/400 μL) of the GGT activatable probe. RESULTS: The GGT activatable probe was activated as early as 5 min after application. Microscopy revealed localization predominantly in the cytosol. Expression of GGT was higher in colon cancer cells than in normal human colon cells. With In Vivo fluorescence micro-colonoscopy, it was possible to detect lesions as early as 5 minutes after intrarectal administration of the probe, and fluorescence lasted at least 30 minutes with high signal-to-background ratios. By switching to white light imaging, fluorescent lesions could be superimposed on sites of tumor. Fluorescence guided biopsy revealed that all fluorescent lesions contained cancer and/or low-to-high grade dysplasia (n = 16), whereas 3 out of 12 non-fluorescent lesions contained low grade dysplasia while the remainder showed no neoplasia/dysplasia. Furthermore, tumor progression in the same mouse could be followed by repeat micro-colonoscopy after application of the GGT activatable probe. CONCLUSIONS: These results indicate that it is possible to enhance the detection of CAC using a GGT activatable probe during endoscopy. This could have broad implications for the early detection of patients with long standing bowel inflammation who are at increased risk for the development of colon cancer.

Three modes of cancer therapy, surgery, radiation and chemotherapy, have been central to modern oncologic therapy. Molecular targeted cancer therapies have been introduced to target specific pathways, while minimizing side effects but have had limited success except in several notable cases. The concept of amplifying the effect of molecular targeting by applying physical energy to the bound conjugate is relatively new. In this study, we describe a hydrophilic photosensitizer based on a near infrared (NIR) phthalocyanine dye, IR700, which is covalently conjugated to one of several humanized monoclonal antibodies (MAb) targeting human epidermal growth factor receptor (EGFR) type 1 (HER1) and 2 (HER2). When exposed to light the conjugate induces highly selective cell death in vivo, a process termed “photo-activatable immunotherapy” (PIT). In vitro studies were conducted with Trastuzumab-IR700 bound to HER2-expressing NIH3T3 cells (3T3/HER2) and panitumumab-IR700 bound to HER1-expressing A431 cells which were then irradiated with non harmful NIR light. EGFR-negative Balb3T3 cells were used as controls. In vivo studies were conducted with 3T3/HER2 and A431 xenograft tumors 1 day after intravenous administration of MAb-IR700 followed by non harmful, transcutaneous NIR light. MAb-IR700 demonstrated specific binding to target receptors on the cell membrane, which was followed by gradual internalization into endolysosomal compartments. MAb-IR700 bound target-specific cell death could be induced within 5 minutes of exposure to NIR light and resulted in cellular swelling, bleb formation, and rupture of vesicles indicating necrotic cell death. No phototoxicity was observed in co-cultured receptor-negative Balb3T3 cells after incubation with MAb-IR700, even when MAb-IR700 was not removed from the medium during light exposure. EGFR target-specific accumulation of MAb-IR700 was observed in the mouse xenograft tumors on NIR fluorescence images. Greater than 90% tumor shrinkage within 3 days of the NIR irradiation, was measured, with no apparent side effects, but was only observed in EGFR-expressing tumors. Furthermore, IR700 fluorescence produced by the MAb conjugate permitted guidance of light delivery and allowed for monitoring after therapy. The MAb-IR700 PIT was most effective, when conjugates were bound to the cell membrane, but showed no phototoxicity, when unbound, suggesting a novel mechanism for PIT compared with conventional photodynamic therapies. Target selective PIT based on MAb-IR700 conjugate membrane binding enables selective treatment of cancer with no apparent side effect to normal cells or surrounding tissue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3618. doi:10.1158/1538-7445.AM2011-3618

The concentration of carcinoembryonic antigen (CEA), CA130, CA125, SLX, CA19-9, SPan1, and tumour-associated glycoprotein 72 (TAG-72) in the culture supernatant of 15 cancer cell lines and in the sera of 58 cancer patients was measured, and the co-expression of these antigens was examined by double determinant immunoradiometric assays. The high correlation coefficient of the concentrations and significant binding in the double determinant assays indicated a close relationship between CA125 and CA130 and between CA19-9 and SPan1. There was variable binding of the 125I-labelled anti-SLX, anti-CA19-9, and anti-SPan1 antibodies to anti-CA130 beads that had been pre-incubated with the culture supernatants, suggesting the presence of the epitopes of SLX, CA19-9, and SPan1 on the molecule expressing CA130. Similarly, the epitopes of SLX, CA19-9, and SPan1 could be present on the molecule expressing CEA. 125I-labelled anti-CA19-9, anti-SLX, and anti-TAG-72 antibodies were bound in variable proportions to anti-CA130 beads or to anti-CEA beads that had been pre-incubated with patients' sera. However, CEA and CA130 were not expressed on the same molecule, either in the culture supernatant, or in patients' sera. In conclusion, the carbohydrate epitopes of CA19-9, SPan1, SLX, and TAG-72 could be present on the molecule recognised by the anti-CA130 or anti-CEA antibody; however, the epitopes of CA130 and CEA did not co-exist on the same molecule.

Word limit: 2600 characters, including abstract body and title. Optical imaging has the potential to become a robust tool in intraoperative sentinel lymph node mapping because of its portability, high spatial resolution, and absence of radiation. Most preclinical and clinical studies have used conventional fluorescent agents, which need excitation light to emit fluorescence. However, excitation light also induces autofluorescence (background signal) from intrinsic fluorophores in the normal tissue, lowering the target-to-background ratio. We developed two new methods for optical sentinel lymph node mapping to eliminate background signals using two unique nano-particles; an upconverting nano-particle (UCNP) and a self-illuminating bioluminescence resonance energy transfer quantum-dot (BRET-QD) nano-particle. UCNPs are unique nano-sized particles that emit light at shorter wavelengths with excitation in the near infrared (NIR). Since fluorophores typically emit light at longer wavelengths than the excitation light, there is no autofluorescence. Moreover, by changing the composition of the doping metals, UCNPs can be designed to emit at specific wavelengths. When UCNPs were injected into the chin of anesthetized mice, and excited at 950-nm, superficial neck lymph nodes were successfully depicted with no background signals in the visible-range (peak 550 nm) or NIR-range (peak 800 nm) in all mice. Furthermore, with serial injection of the visible and NIR-range UCNPs, simultaneous lymphatic imaging was achieved in two colors. The BRET-QD is self-illuminating and employs the substrate, coelenterazine, which reacts with luciferase conjugated on the BRET-QD. The bioluminescent light in blue efficiently excites the NIR QD, and emits photons in the NIR, therefore, there is no autofluorophore excitation. Moreover, by changing the QDs within BRET-QD, it is possible to alter their emission wavelength. BRET-QD655, (QD655 in its core), was injected at different sites (chin, ear, forepaws, and hind paws) of anesthetized mice. After BRET-QD655 injection, coelenterazine was intravenously injected and imaging was performed without excitation light. In all mice, sentinel lymph nodes in each lymphatic basin were clearly visualized with ultra-low background signals, and lasted at least 30 min after coelenterazine injections. In conclusion, we demonstrate that optical imaging using two unique nano-particles were able to depict sentinel lymph nodes with minimal autofluorescence. This enables the direct, real time sentinel lymph node mapping without extensive post processing of the images. These two novel nano-particles have the potential to be robust tools for sentinel lymph node detection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4332.

A case of primary retroperitoneal plasmacytoma causing a tumor thrombus within the renal vein is described. The use of radiographic techniques, including ultrasonography, computerized tomography and angiography, facilitated an accurate diagnosis. Tumor thrombi within the renal vein are rare except in cases of primary renal or adrenal neoplasms. In a patient with radiological evidence of retroperitoneal tumor and tumor thrombus within the renal vein plasmacytoma should be considered in the differential diagnosis of retroperitoneal neoplasms.

Fluorophores are potentially useful for in vivo cancer diagnosis. Using relatively inexpensive and portable equipment, optical imaging with fluorophores permits real-time detection of cancer. However, fluorophores can be toxic and must be investigated before they can be administered safely to patients. A review of published literature on the toxicity of 19 widely used fluorophores was conducted by searching 26 comprehensive biomedical and chemical literature databases and analyzing the retrieved material. These fluorophores included Alexa Fluor 488 and 514, BODIPY FL, BODIPY R6G, Cy 5.5, Cy 7, cypate, fluorescein, indocyanine green, Oregon green, 8-phenyl BODIPY, rhodamine 110, rhodamine 6G, rhodamine X, rhodol, TAMRA, Texas red, and Tokyo green. Information regarding cytotoxicity, tissue toxicity, in vivo toxicity, and mutagenicity was included. Considerable toxicity-related information was available for the Food and Drug Administration (FDA)-approved compounds indocyanine green and fluorescein, but published information on many of the non-FDA-approved fluorophores was limited. The information located was encouraging because the amounts of fluorophore used in molecular imaging probes are typically much lower than the toxic doses described in the literature. Ultimately, the most effective and appropriate probes for use in patients will be determined by their fluorescent characteristics and the safety of the conjugates.

Upconverting nanocrystals are unique nano-sized particles that emit light at shorter wavelengths (visible and near infrared) after excitation in the near infrared that dramatically reduces background autofluorescence in in vivo two color lymphatic imaging for depicting the lymphatic channels and nodes.

Commonly used in flow cytometry, multiplexed optical probes can diagnose multiple types of cell surface marker, potentially leading to improved diagnosis accuracy in vivo. Herein, we demonstrate the targeting of two different tumor markers in models of disseminated ovarian cancer. Two ovarian cancer cell lines (SKOV3 and SHIN3) were employed; both over-express D-galactose receptor (D-GalR), but only SKOV3 over-expresses HER2/neu. Additionally, fusion tumors composed of SKOV3 and SHIN3/RFP were evaluated. Both galactosyl serum albumin-rhodamine green (GSA-RhodG) which binds D-galR and trastuzumab-Alexa680 which binds HER2/neu were administered to tumor bearing mice for in vivo fluorescence imaging and in situ fluorescence microscopy. In vivo fluorescence imaging depicted 64 of 69 SKOV3 tumors (94.2%) based on their dual spectra corresponding to both RhodG and Alexa680, while all 71 SHIN3 tumors (100%) were detected based on their single spectrum corresponding only to RhodG. All 59 SHIN3 and 36 SKOV3 tumors were correctly diagnosed with in situ microscopy. Additionally, in the mixed tumor model, all tumors could be depicted using the RhodG spectrum, but only SKOV3 components also showed the Alexa680 spectrum. In conclusion, multi-targeted multi-color optical imaging enabled specific in vivo diagnosis of tumors expressing distinct patterns of receptors, leading to improved diagnostic accuracy.

Optical imaging is unique among in vivo imaging methods because it is possible to simultaneously resolve two or more probes emitting at different wavelengths of light. We employed two near-infrared (NIR) fluorescent optical probes, each labeled with a different protein, to simultaneously evaluate the pharmacokinetics of each probe. Dynamic optical imaging was performed in live mice after the coinjection of bovine serum albumin (BSA) and galactosamine-conjugated bovine serum albumin (GmSA) labeled with either Cy5.5 or Cy7 NIR dyes. The pharmacokinetics of BSA and GmSA were independently and simultaneously visualized. Next, two-color dynamic imaging of biotinylated BSA (b-BSA) and BSA labeled with Cy5.5 or Cy7 was performed before and after an avidin "chase." Following avidin injection, fluorescently labeled b-BSA rapidly accumulated in the liver, while minimal liver uptake of BSA was noted. Thus, multicolor dynamic contrast-enhanced optical imaging can be performed to noninvasively track the pharmacokinetics of different proteins. This imaging technique can be applied to a wide variety of optically labeled proteins in order to simultaneously track their biodistribution.

The wavelength resolved spectral fluorescence imaging technique using a fluorescein-conjugated avidin has been reported to visualize submillimeter implants of ovarian cancer because of its highly targeted and quickly cleared pharmacokinetics. However, clinical application of avidin was hampered by its strong immunogenicity. As a clinically feasible alternative to avidin, which targets the same D-galactose receptor but is made from a nonimmunogenic source, with even better binding capability by multiplying binding sites but still maintaining a favorable characteristic of high isoelectric point, a serum albumin conjugated with 23 galactosamine and 2 rhodamine green molecules (GmSA-RhodG) was designed and synthesized. GmSA-RhodG showed more than 10-fold rapid and higher uptake by SHIN3 ovarian cancer cells than both avidin- and no galactosamine-conjugated albumin (bovine serum)-RhodG. Sensitivity and specificity of GmSA-RhodG to detect red fluorescence labeled peritoneal cancer foci in mouse cancer model were 100%/99% (n=566), respectively for approximately 1-mm lesions and even smaller lesions were detected in vivo. These results indicate that GmSA-RhodG is not only a clinically feasible alternative but more efficient targeting reagent for D-galactose receptors than avidin-RhodG.

PAMAM dendrimer-based biometric nanoprobes G4-1B4M-Gd, G6-1B4M-Gd and G8-1B4M-Gd were used to detect vascular permeability in SCCVII mice tumors. Based on the whole body clearance curve, G8-1B4M-Gd emerged as the ideal candidate for vascular permeability imaging studies due to its stable signal enhancement in the tumor over time. A 2D MR image of a SCCVII tumor showed vessel enhancement without obvious diffuse enhancement.

Two forms of formaldehyde dismutase distinguishable on disc-gel electrophoresis were isolated from the cell-free extract of Pseudomonas putida F61. The mobilities on SDS-gel electrophoresis and the NH2-terminal amino acids (arginine) of the two enzyme species were identical. The COOH-terminal amino acid sequence was found to be -Ser-Gly-Lys. The enzyme was inhibited by carbonyl, reducing and sulfhydryl reagents.The enzyme catalyzed the cross-dismutation reaction between formaldehyde and an aldehyde, such as propionaldehyde, acrolein, butyraldehyde, isobutyraldehyde and crotonaldehyde. The enzyme also catalyzed a coupled oxidoreduction between an alcohol and an aldehyde (RCH2OH+R'CHO RCHO +R'CH2OH) without addition of an electron acceptor. Aliphatic alcohols and aldehydes of C2 to C4 were utilized in this reaction.

The concept 'authoritarianism' has several meanings. But its most important meaning lies in the combination of 'authoritarian aggression' (aggression to powerless persons) and 'authoritarian submission' (submission to powerful persons). Reviewing the studies of Adorno et al., Rokeach and Eysenck, we find that this basic meaning of authoritarianism is closely connected with conservatism. This paper presents a theoretical framework to account for this linkage between authoritarianism and conservatism. Our framework derives from purely theoretical consideration, and it also shows the interrelationships between several concepts such as 'authoritarianism', 'revolutionist', 'nihilism', 'extremism', 'moderates', 'defeatism', 'conservatism', and 'progressivism'. Next, the problem of 'left-authoritarianism' posed by Shils is discussed. To consider this problem, the following three points are important. (1) Whether the 'left-wingers' live in a capitalistic society or a communist society. 'Leftists' in a capitalistic society and 'leftists' in a communist society are not in the same positson. (2) Whether the analysis is concerned with the leftists' attitudes toward the socioeconomic system as a whole or toward specific organizations they belong. They are the attitudes to different objects, so we must discriminate between the former and the latter. (3) Whether the focus is on their personality or on their attitude. We should not confuse the problem of personality with the problem of attitude. Considering these points, we conclude that in capitalistic societies, 'left-wingers' may be 'extremists' but that 'right-wingers' are more 'authoritarian' than 'left-wingers'.

Formaldehyde-resistant Pseudomonas putida F61 isolated from a soil sample showed high activities of formaldehyde dehydrogenase (EC 1.2.1.1) and a specific enzyme catalyzing the dismutation of formaldehyde to form methanol and formate. The latter enzyme, given the trivial name of formaldehyde dismutase, was purified to electrophoretic homogeneity from a cell-free extract of P. putida F61. The enzyme was a tetramer with a molecular weight of approximately 2.2 × 105, and an isoelectric point of 4.8. The enzyme catalyzed the stoichiometric dismutation of formaldehyde and acetaldehyde to form a half mol of each of the corresponding alcohol and acid without addition of an electron acceptor, but it did not catalyze the dismutation of pro-pionaldehyde, butyraldehyde and so on. The apparent Km for formaldehyde was found to be 350 mM. One of the most unique properties of the enzyme was the catalytic activity of cross-dismutation between two different aldehydes, such as formaldehyde/acetaldehyde, formaldehyde/ propi...

To map the drainage patterns of the lymphatic system, multicolor optical probes must be developed, which can be interstitially administered. These agents must be of sufficient size to be retained by the lymphatic system and permit the conjugation or incorporation of fluorescent probes with varying emission wavelengths. Quantum dots fulfill these criteria, but their potential toxicity limits their application to research settings. Here, we describe the synthesis of lymphatic optical probes based on Igs conjugated with Cy5.5 and Cy7 and demonstrate in animal models that these agents can map the lymphatic drainage patterns within axillary nodes draining both the breast and upper extremity, cervical nodes draining both the ear and upper extremity, and sentinel lymph nodes draining different anatomic locations. The ability to separately and simultaneously visualize the drainage patterns from two separate lymphatic vessels may have implications for the preoperative mapping of lymph nodes before lymph node resection. The biocompatibility of fluorescently labeled Igs in comparison to other nanoparticulate fluorophores improves the chances of clinical translation. This noninvasive and biocompatible multicolor method of optical lymphangiography may elucidate the complex human lymphatic system and reduce the risk of lymphedema after surgery for melanoma and other cancers.

Molecular imaging of cell surface receptors can potentially diagnose tumors based on their distinct expression profiles. Using multifilter spectrally resolved optical imaging with three fluorescently labeled antibodies, we simultaneously imaged three different cell surface receptors to distinguish tumor types noninvasively. We selected tumors overexpressing different subtypes of EGFR receptor: HER-1 (A431) and HER-2 (NIH3T3/HER2(+)), or interleukin-2 receptor alpha-subunit receptor (IL-2Ralpha; SP2/Tac). After tumor establishment, a cocktail of three fluorescently labeled monoclonal antibodies was injected: cetuximab-Cy5 (targetingHER-1), trastuzumab-Cy7(HER-2),anddaclizumab-AlexaFluor-700 (IL-2Ra). Optical fluorescence imaging was performed after 24 hours with both a red filter set and three successive filter sets (yellow, red, and deep red). Spectrally resolved imaging of 10 mice clearly distinguished A431, NIH3T3/HER2(+), and SP2-Tac tumors based on their distinct optical spectra. Three-filter sets significantly increased the signal-to-background ratio compared to a single-filter set by reducing the background signal, thus significantly improving the differentiation of each of the receptors targeted (P < .022). In conclusion, following multifilter spectrally resolved imaging, different tumor types can be simultaneously distinguished and diagnosed in vivo. Multiple filter sets increase the signal-to-noise ratio by substantially reducing the background signal, and may allow more optical dyes to be resolved within the narrow limits of the near-infrared spectrum.

Detection of inflammation following renal ischemia by magnetic resonance imaging. Background Determining the disease culprits in human acute renal failure (ARF) has been difficult because of the paucity of renal biopsies and the lack of noninvasive methods to determine the location or cause of renal injury. Recently, ultrasmall superparamagnetic iron oxide (USPIO) particles have been used to detect inflammation in animal models. Therefore, we tested if USPIO enhanced magnetic resonance imaging (MRI) could detect inflammation in ischemic ARF in rats. Methods Rats were subjected to 40 or 60 minutes of bilateral ischemia or injected with mercuric chloride. MR images were obtained before and 24hours after USPIO injection, and the signal intensity decrease in the outer medulla was measured. Cells containing iron particles were identified by iron staining and transmission electron microscopy (TEM). Leukocytes were identified by ED-1 and chloracetate esterase staining. Results Injection of USPIO particles caused a black band to appear in the outer medulla at 48, 72, and 120hours after ischemia. This band was not detected in normal animals, 24hours after ischemia, or 48hours after mercuric chloride injection. The signal intensity change in the outer medulla correlated with serum creatinine and the number of iron particle containing cells. Most infiltrating cells were macrophages, and iron particles were present inside lysosomes of macrophages. USPIO injection did not alter renal function in normal or ischemic animals. Conclusion USPIO-enhanced MRI could detect inflammation noninvasively from 48hours after 40 or 60 minutes of renal ischemia in rats. This method might be useful to understand the pathogenesis of human ARF and to evaluate the effectiveness of anti-inflammatory agents.

A mutant, No. 65, of Hansenula polymorpha CBS 4732 was isolated which was impaired in its ability to grow on methanol and dihydroxyacetone. Mutant No. 65 produced dihydroxyacetone and glycerol from methanol with a 18.8% yield in a resting-cells reaction. The absence of dihydroxyacetone kinase activity in the mutant is believed to be the reason for its inability to grow on methanol and for the accumulation of trioses. This mutant, however, was able to grow on glycerol, and dihydroxyacetone kinase was found in the cells. The growth on glycerol was almost completely inhibited by the addition of methanol (0.1% v/v). As far as tested with partially purified enzymes, no property was found that could be used to distinguish between the kinases from methanol- and glycerol-grown cells. The evidence suggests that the phenotype of No. 65 is a lesion not in the structural gene but in its regulatory gene.

Background Near infrared (NIR) photoimmunotherapy (PIT) is a new type of cancer treatment based on a monoclonal antibody (mAb)-NIR phthalocyanine dye, (IR700) conjugate. In vitro cancer-specific cell death occurs during NIR light exposure in cells previously incubated with mAb-IR700 conjugates. However, documenting rapid cell death in vivo is more difficult. Methods A luciferase-transfected breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells) was produced and used for both in vitro and in vivo experiments for monitoring the cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up to 8 J/cm2 in vitro, we employed an orthotopic breast cancer model of bilateral MDA-MB-468luc tumors in female athymic mice, which subsequently received a panitumumab-IR700 conjugate in vivo. One side was used as a control, while the other was treated with NIR light of dose ranging from 50 to 150 J/cm2. Bioluminescence imaging (BLI) was performed before and after PIT. Results Dose-dependent cell killing and regrowth was successfully monitored by the BLI signal in vitro. Although tumor sizes were unchanged, BLI signals decreased by >95% immediately after PIT in vivo when light intensity was high (>100 J/cm2), however, in mice receiving lower intensity NIR (50 J/cm2), tumors recurred with gradually increasing BLI signal. Conclusion PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo.

Intraperitoneal metastases commonly recur after surgery because small tumor foci escape detection within the complex anatomy of the peritoneal cavity and mesentery. Accurate localization of peritoneal implants during surgery could improve the resection of ovarian cancer and other malignancies, but few practical techniques to enhance detectability are currently available. Here, we describe a targeted molecular imaging method that employs fluorescently labeled avidin to detect submillimeter peritoneal implants of ovarian cancer in mice. After binding to surface lectins on the tumor, fluorescein-conjugated avidin enabled the spectral fluorescence imaging of disseminated peritoneal implants. High spatial resolution and high tumor-to-background ratio allowed the visualization of implants as small as 0.3 mm (with 100% sensitivity and specificity; n = 150) and the identification of even smaller lesions ex vivo. These results suggest that targeted molecular imaging with a fluorescence-labeled lectin-ligand system is a promising technique for the detection of disseminated submillimeter foci of cancer.