First Report of Sweet potato virus G Infecting Sweet Potato in Taiwan.

Sweet potato, Ipomoea batatas (L.) Lam., is an important root crop grown mainly in the counties of Changhua, Yunlin, Tainan, and Pingtung in Taiwan where Sweet potato feathery mottle virus (SPFMV) and Sweet potato latent virus (SPLV) have been reported. Commercial sweet potato grown in Nantou in 2009 and in Hualian in 2010 exhibited downward leaf curling and vein clearing, indicative of viral infection, yet symptoms were distinct from those caused by SPFMV, SPLV, or mixed infection of both viruses. Total RNA was extracted from two symptomatic plants from each county with RNeasy Plant Mini Kit (Qiagen, Hilden, Germany) and analyzed by reverse transcription (RT)-PCR using the potyvirusdegenerate primer Hrp5 (1) and oligo-dT18 with BamHI site at the 5' end (5'-GGATCCTTTTTTTTTTTTTTTTTT-3'). Two healthy plants served as negative controls. An approximately 1.5-kb amplicon covering the region from the 3'-end of the nuclear inclusion protein b (NIb) gene to the 3'-untranslated region (3'-UTR) was amplified from all symptomatic plants, while the healthy controls remained negative. Subsequently, one sample from each location was cloned and sequenced (GenBank Accession No. HQ171932-TW1 [Nantou] and JN205346-TW2 [Hualian]). Based on sequence comparison, the two isolates shared only 86.7% nucleotide identity. BLAST analysis of the CP gene of the isolate TW1 revealed 99% nucleotide identity with the corresponding sequence of Sweet potato virus G (SPVG)-CH2 from China (Z83314). Isolate TW2, however, only shared 86% nucleotide identity with SPVG-CH2, indicating isolate TW2 is genetically different from other isolates and probably represents a new strain of SPVG. The presence of SPVG was further confirmed in symptomatic plants by indirect ELISA using SPVG antiserum developed by Y.-H. Cheng of the Agricultural Research Institute. Since co-infection of different viruses in sweet potato can cause severe leaf symptoms and significant yield reduction (3), a preliminary field survey was also conducted to determine the extent of co-infection with more than one potyvirus using three different primer pairs, SPVGup (5'-ACCGAGCTTTACCCCAGGTAGAGAG-3')/SPVdw (5'-CGCGCAAGACTCATRTCAGTCAAAT-3') for SPVG, FM16 (5'-GAATTTAAAGATGCAGGTGTGAAC-3')/FM895 (5'-GAGGTTATGTATATTTCTAGTAAC-3') for SPFMV, and L166 (5'-GACAGAGATATCAACACTGGCACC-3')/L841 (5'-TCCAAGTAGTGTGTGTATGTTCCG-3') for SPLV. Forty-six of 128 (36%) sweet potato samples collected from Nantou, Hualian, Yunlin, Tainan, and Chiayi counties during 2010 and 2011 tested positive for SPVG. Of the 46 samples that tested positive for SPVG, six were co-infected with SPLV, 19 were co-infected with SPFMV, and two were co-infected with all three viruses. Of the samples that tested negative for SPVG, 10 were infected with SPLV, eight were infected with SPFMV, and two were infected with both SPLV and SPFMV. To date, SPVG has been detected in China, the United States, Peru, Egypt, Ethiopia, Zimbabwe, South Africa, Spain, Java, New Zealand, Hawaii, French Polynesia, and Easter Island (2). To our knowledge, this is the first report of SPVG infecting sweet potato in Taiwan. SPVG could become a new and potentially serious threat to sweet potato production in Taiwan. References: (1) C. C. Chen et al. Bot. Stud. 47:369, 2006. (2) M. Rännäli et al. Plant Dis. 92:1313, 2008. (3) M. Untiveros et al. Plant Dis. 91:669, 2007.

First Report of Capsicum chlorosis virus Infecting Amaryllis and Blood Lily in Taiwan.

Capsicum chlorosis virus (CaCV), a thrips-transmitted, tentative species in the genus Tospovirus, family Bunyaviridae, was first identified in solanaceous crops, but also infects several ornamental crops such as orchid (4), gloxinia (3), and calla lily (1). From 2005 to 2007, virus-like yellow ringspots were observed on the leaves of amaryllis (Hippeastrum hybridum Hort.) and blood lily (Haemanthus multiflorus Martyn.) plants cultured in screenhouses and a private garden, respectively. Three of several hundred amaryllis plants in screenhouses from two places were observed as showing yellow ringspot symptoms and one of six blood lily plants was observed as showing similar yellow ringspot symptoms. Sap extracts from symptomatic leaves were inoculated to Chenopodium quinoa Willd. and the resulting local lesions were passaged three successive times to C. quinoa for virus isolation. Using the tospovirus genus-specific primers gL3637 and gL4435c designed from the conserved region in the L RNA (2), DNA fragments of the expected size of 800 bp were amplified by reverse transcription (RT)-PCR from field samples and local lesions from C. quinoa. Extracts from the diseased plants and local lesions of C. quinoa reacted strongly with antiserum against the nucleocapsid (N) protein of CaCV in ELISA and western blotting. To confirm the identity of this virus, we amplified the N gene from three amaryllis and one blood lily source using primer pair WN2328 and WN3534 designed from the S RNA of Watermelon silver mottle virus (1), and these products were cloned and sequenced. The sequence from each virus isolate was determined from three independent clones. The nucleotide and deduced amino acid sequences of N genes for the blood lily isolate (GenBank Accession No. EF101344) and three amaryllis isolates (GenBank Accession Nos. EF101343, EF137177, and FJ185170) had identities greater than 97% with that of a CaCV isolate infecting Capsicum spp. found in Australia (GenBank Accession No. AY036057). Phylogenetic analysis using maximum parsimony showed that these sequences clustered with CaCV. These results show that the virus identified from amaryllis and blood lily that were expressing yellow ringspot symptoms are isolates of CaCV. To our knowledge, this is the first report of CaCV naturally infecting amaryllis and blood lily and it could become an important threat to ornamental production in Taiwan. References: (1) C. C. Chen et al. Plant Dis. 91:1201, 2007. (2) F. H. Chu et al. Phytopathology 91:361, 2001. (3) H. T. Hsu et al. J. Gen. Plant Pathol. 66:167, 2000. (4) Y. X. Zheng et al. Eur. J. Plant Pathol. 120:199, 2008.

Potential threat of a new pathotype of Papaya leaf distortion mosaic virus infecting transgenic papaya resistant to Papaya ringspot virus.

A virus identified as a new pathotype of Papaya leaf distortion mosaic virus (PLDMV, P-TW-WF) was isolated from diseased papaya in an isolated test-field in central Taiwan, where transgenic papaya lines resistant to Papaya ringspot virus (PRSV) were evaluated. The infected plants displayed severe mosaic, distortion and shoe-stringing on leaves; stunting in apex; and water-soaking on petioles and stems. This virus, which did not react in enzyme-linked immunosorbent assay with the antiserum to the PRSV coat protein, infected only papaya, but not the other 18 plant species tested. Virions studied under electron microscope exhibited morphology and dimensions of potyvirus particles. Reverse transcription-polymerase chain reaction conducted using potyvirus-specific primers generated a 1,927-nucleotide product corresponding to the 3' region of a potyvirus, showing high sequence identity to the CP gene and 3' noncoding region of PLDMV. Search for similar isolates with the antiserum against CP of P-TW-WF revealed scattered occurrence of PLDMV in Taiwan. Phylogenetic analysis of PLDMV isolates of Taiwan and Japan indicated that the Taiwan isolates belong to a separate genetic cluster. Since all the Taiwan isolates infected only papaya, unlike the cucurbit-infecting Japanese P type isolates, the Taiwan isolates are considered a new pathotype of PLDMV. Susceptibility of all our PRSV-resistant transgenic papaya lines to PLDMV indicates that the virus is an emerging threat for the application of PRSV-resistant transgenic papaya in Taiwan and elsewhere.

First Report of Capsicum chlorosis virus Causing Yellow Stripes on Calla Lilies in Taiwan.

Tomato spotted wilt virus (TSWV) and Calla lily chlorotic spot virus (CCSV) are two recognized species of the Tospovirus genus in the family Bunyaviridae infecting calla lily (Zantedeschia spp.). During 2005, 15 virus isolates were collected from different calla lily plants exhibiting yellow stripes on their leaves in Ho-Li, a major calla lily-production township in Taiwan. After three successive local lesion passages on Chenopodium quinoa Willd., diseased leaf tissues individually infected by these isolates were preserved in liquid nitrogen and used for subsequent identification studies. Using the tospovirus genus-specific primers gL3637 and gL4435c designed from the L RNA, an 800-bp DNA fragment was amplified in reverse transcription-PCR from all 15 isolates. Moreover, leaf extracts of the diseased calla lilies and the C. quinoa plants inoculated with the 15 virus isolates reacted with antisera against the nucleocapsid proteins (NP) of Capsicum chlorosis virus (CaCV)-gloxinia and Watermelon silver mottle virus (WSMoV), but not to monoclonal antibodies against the NP of TSWV, CCSV, Peanut chlorotic fan-spot virus (PCFV), or Impatiens necrotic spot virus (INSV) in indirect ELISA. These results indicate that the 15 virus isolates are tospoviruses belonging to the WSMoV serogroup. Additionally, we amplified and sequenced the full-length N gene from these tospovirus isolates using primers WN2328 (5'-CCATTGGTTTGCCTCCG-3') and WN3534 (5'-CGTCGACAGAGCAATCGAGGC-3') designed from the S RNA of WSMoV. The deduced amino acid sequences of the N protein from these 15 tospovirus isolates showed a greater than 92% identity to that of CaCV (GenBank Accession No. NC-008301). Furthermore, results of phylogenetic analysis of the 15 isolates on the basis of amino acids sequences, both genetic distance and parsimony trees indicated that they were all genetically clustered within CaCV using INSV, TSWV, and WSMoV as outgroups. The results indicate that the virus causing yellow stripes in calla lilies is a strain of CaCV. To our knowledge, this is the first evidence that CaCV can naturally infect calla lilies and cause yellow stripe symptoms. Reference: (1) F.-H. Chu et al. Phytopathology 91:361, 2001.

Phase I and imaging trial of indium 111-labeled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma.

Murine monoclonal antibody (MAb) 225 (IgG1) against the epidermal growth factor (EGF) receptor competitively blocks EGF binding and inhibits EGF-induced activation of receptor tyrosine kinase and cell proliferation. The effect of MAb 225 was studied in a phase I trial in patients with inoperable squamous cell carcinoma of the lung, which invariably expresses high levels of EGF receptors. Groups of three patients received total doses of MAb 225 ranging from 1 mg to 300 mg. Except at the lowest dose, each infusion included 4 mg of indium 111 (111In)-labeled MAb 225. No toxicity was observed. Tumors were imaged in all patients who received doses of 20 mg or greater. Presumed metastases greater than or equal to 1 cm in diameter were imaged with doses of 40 mg or greater. Single-photon-emission-computed tomography could be carried out at the 120-mg and 300-mg doses and significantly improved tumor visualization. All patients produced anti-murine antibodies. We conclude that treatment with an MAb that inhibits EGF receptor function is safe at the doses and schedule studied. 111In-labeled MAb images squamous cell lung carcinoma; tumor uptake of the labeled MAb is dose dependent. Further studies are warranted to explore the potential therapeutic efficacy of anti-EGF receptor MAbs and other agents that act in a comparable manner.

A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: effects of tumor burden and antigen expression.

Eighteen patients with relapsed non-Hodgkin's lymphoma (NHL) were infused with escalating doses of monoclonal antibody (mAb) OKB7, trace-labeled with iodine-131 (131I), in order to study toxicity, pharmacology, antibody localization, and dosimetry of radioiodine. OKB7 is a noncytotoxic mouse immunoglobulin G2b (IgG2b) mAb reactive with B cells and most B-cell NHL. Three patients each were treated at six dose levels ranging from 0.1 mg to 40 mg. All patients had radionuclide imaging and counting daily, had serial blood sampling to study pharmacokinetics, human antimouse antibody (HAMA), and circulating antigen, and had a biopsy of accessible lymphoma to determine delivery of isotope to tumors and assess the effect of tumor antigen expression on mAb delivery. Bone marrow biopsies were also done in the majority of patients. There was no toxicity. Serum clearance showed a median early phase half-life of 1.9 hours and a later phase half-life of 21.7 hours. Median total body clearance half-life was 22 hours. Pharmacokinetics were not dose-related. HAMA was detected in five patients. Circulating blocking antigen was detected in the serum of four patients, but at levels that were of pharmacologic consequence only in one. Biopsied tumor tissue from five patients did not express OKB7 antigen. No significant uptake of antibody was seen in these tumor sites. Mean total uptake of isotope into lymphoma measured in biopsies correlated linearly over the 400-fold increase in injected mAb dose. However, the percent of injected dose found per gram of tumor was unrelated to dose, but correlated inversely with tumor burden. In two patients with minimal tumor burden, 1.0 mg and 5.0 mg doses of OKB7 resulted in tumor to body radioisotope dose ratios of 22 and 7, which would theoretically permit tolerable delivery of 4,400 and 1,400 rads to these tumors, respectively, if OKB7 were conjugated with higher doses of 131I.

Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33.

A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear.

Survival from locally invasive or widespread neuroblastoma without cytotoxic therapy.

PURPOSE: To test the hypothesis that cytotoxic therapy is not needed at diagnosis to assure the survival of most patients with non-stage 4 neuroblastoma. METHODS: Patients with non-stage 4 disease received no cytotoxic therapy in the absence of N-myc amplification. The International Neuroblastoma Staging System (INSS) was used. RESULTS: Of 84 consecutive patients with previously untreated, newly diagnosed neuroblastoma, 31 (37%) had non-stage 4 disease. All 31 patients initially received no cytotoxic therapy because none of them had N-myc amplification. Nine stage 1 patients are relapse-free. This report focuses on the 22 patients with locally invasive or distant disease: two stage 2A with gross residual tumor postsurgery, 11 stage 2B with ipsilateral or midline lymph node involvement, four stage 3, and five stage 4S. Eight of the 22 patients were older than 1 year. Postsurgery, 13 patients had visible residual disease, and two others had markedly increased urinary catecholamine levels for more than 1 year. Recurrent or enlarging tumors regressed spontaneously (n = 2) or were excised 5 to 39 months after diagnosis (n = 4). One of the latter had chromosome 1p deletions (common in poor-risk neuroblastoma) that were not detected in the patient's original tumor resected 23 months earlier--findings consistent with clonal evolution or multifocal disease. The patient received chemotherapy. All 22 patients are alive 24 to 98 months (median, 64) from diagnosis. CONCLUSION: Our results suggest that non-stage 4 patients without N-myc amplification can be spared cytotoxic therapy because (1) residual postsurgical or recurrent biologically favorable neuroblastoma rarely evolves into lethal stage 4 disease; and (2) neuroblastoma in lymph nodes has no prognostic significance. These findings are remarkable because no other cancer includes subtypes that are curable without therapy to ablate residual disease.

Rhenium-186-labeled hydroxyethylidene diphosphonate dosimetry and dosing guidelines for the palliation of skeletal metastases from androgen-independent prostate cancer.

Rhenium-186 (tin)-labeled hydroxyethylidene diphosphonate (186Re-labeled HEDP) was evaluated in 27 men with progressive androgen-independent prostate cancer and bone metastases. Administered activities ranged from 1251 to 4336 MBq (33.8-117.2 mCi). The primary objectives were to assess tumor targeting, normal organ dosimetry, and safety. Antitumor effects were assessed by posttherapy changes in prostate-specific antigen and, when present, palliation of pain. Whole-body kinetics, blood and kidney clearance, skeletal dose, marrow dose, and urinary excretion of the isotope were assessed. Targeting of skeletal disease was observed over the period of quantification (4-168 h). Radiation doses to whole body, bladder, and kidney were well tolerated. The dose-limiting toxicity was myelosuppression (grade III) at 4107 MBq (111 mCi) and grade II at 296 MBq (80 mCi). Probe clearance (whole body) and urinary excretion measurements were highly correlated. Of the six patients treated at the highest dosage schedules (three at 1510 MBq/m2 and three at 1665 MBq/m2), three showed a posttherapy decline in prostate-specific antigen of 50% or more. The declines were not sustained. The determination of total activity retained at 24 h, as well as an estimate of marrow dose, correlated with the amount of myelosuppression observed. These results suggest that a single 24-h measurement of retained activity would allow individualized dosing and an improved therapeutic index relative to fixed dosing schema. Repetitive dosing is required to increase palliation.

Lack of correlation of functional scintigraphy with (99m)technetium-methoxyisobutylisonitrile with histological necrosis following induction chemotherapy or measures of P-glycoprotein expression in high-grade osteosarcoma.

In osteosarcoma, some studies have suggested P-glycoprotein expression is a prognostic factor. The clearance of (99m)technetium hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been used in some tumor systems as an in vivo measure of P-glycoprotein-mediated efflux. In this study we explored the correlation between (99m)Tc-MIBI clearance and histological necrosis following induction chemotherapy and P-glycoprotein expression in osteosarcoma. The primary tumors of 20 patients with high-grade osteosarcoma were imaged at diagnosis with (99m)Tc-MIBI, and the uptake ratios and biological half-lives were calculated. P-Glycoprotein expression in the tumor tissue was determined immunohistochemically and by measuring mRNA expression of the multidrug resistance-1 gene. The histological necrosis following induction chemotherapy was assessed by the Huvos grading system. The biological half-life of (99m)Tc-MIBI ranged from 1.4 to 52.5 h. Seven of the 20 tumor samples had a favorable extent of necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio showed no correlation with histological necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio did not correlate with either measure of P-glycoprotein expression. The results of this pilot study indicate that (99m)Tc-MIBI imaging is not an effective predictor of histological necrosis following induction chemotherapy in high-grade osteosarcoma. (99m)Tc-MIBI imaging did not correlate with measures of P-glycoprotein expression in the tumor tissue.

A Chlorotic Spot Disease on Calla Lilies (Zantedeschia spp.) Is Caused by a Tospovirus Serologically but Distantly Related to Watermelon silver mottle virus.

A new tospovirus, Calla lily chlorotic spot virus (CCSV), was isolated from calla lilies (Zantedeschia spp.) in Taiwan. Chlorotic spots, ranging from light green to yellow, appear on the middle leaves of the affected plants. Virions measuring 75 to 105 nm, similar in size to tospovirus particles, were present in crude extracts and ultrathin sections of diseased leaves. Of 35 plant species inoculated mechanically, 24, including wax gourd (Benincasa hispida) and zucchini squash (Cucurbita pepo), were susceptible to the virus. CCSV was transmitted from infected wax gourd by Thrips palmi to healthy wax gourd and zucchini squash. The virus was weakly related to Watermelon silver mottle virus (WSMoV) in enzyme-linked immunosorbent assay (ELISA) and western blot tests. WSMoV-specific N gene primers, however, failed to produce DNA fragments from total RNA extracts of CCSV-infected plants in reverse transcription-polymerase chain reaction (RT-PCR). Results of RT-PCR show that the conserved regions of the L genes of tospoviruses are present in CCSV.

[18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography localizes residual thyroid cancer in patients with negative diagnostic (131)I whole body scans and elevated serum thyroglobulin levels.

Progressive dedifferentiation of thyroid cancer cells leads to a loss of iodine-concentrating ability, with resultant false negative, whole body radioactive iodine scans in approximately 20% of all differentiated metastatic thyroid cancer lesions. We tested the hypothesis that all metastatic thyroid cancer lesions that did not concentrate iodine, but did produce thyroglobulin (Tg), could be localized by [18F]2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET). We performed FDG-PET on 37 patients with differentiated thyroid cancer after surgery and radioiodine ablation who had negative diagnostic 131I whole body scans during routine follow-up. Serum Tg, Tg autoantibodies, neck ultrasounds, and other clinically indicated imaging procedures were performed to detect residual disease. In those with elevated Tg levels, FDG-PET localized occult disease in 71%, was false positive in one, and was false negative in five patients. The majority of false negative FDG-PET occurred in patients with minimal cervical adenopathy. Surgical resections, biopsies, 131 therapy, and differentiation therapy were performed based on the PET results. The FDG-PET result changed the clinical management in 19 of the 37 patients. In patients with elevated Tg levels, FDG-PET had a positive predictive value of 92%. In patients with low Tg levels, FDG-PET had a negative predictive value of 93%. No FDG-PET scans were positive in stage I patients; however, they were always positive in stage IV patients with elevated Tg levels. An elevated TSH level (i.e. hypothyroidism) did not increase the ability to detect lesions. FDG-PET is able to localize residual thyroid cancer lesions in patients who have negative diagnostic 131I whole body scans and elevated Tg levels, although it was not sensitive enough to detect minimal residual disease in cervical nodes.

111Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases.

Abnormal CSF flow can impair the distribution of intrathecally administered drugs. We examined the relationship between 111indium-diethylenetriamine pentaacetic acid (111In-DTPA) CSF flow studies and methotrexate levels in ventricular and lumbar CSF and correlated these findings with outcome in patients with leptomeningeal metastases (LM). Seven men and 10 women with LM (10 solid tumors, 6 lymphoma, 1 leukemia) received 12 mg methotrexate and 0.5 mCi 111In-DTPA by intra-Ommaya injection; images were obtained immediately and after 4, 24, and 48 hours. Ventricular and lumbar CSF methotrexate and radioactivity levels were measured 6 hours after injection. Thirteen patients had abnormal CSF flow studies, 9 with multiple sites of obstruction. CSF flow obstruction was observed at ventricular outlets in 13 patients, cerebral convexities in 9 and in the spine in 2. With one exception, all obstructions were explicable by tumor deposits on MRIs. For all patients, ventricular and lumbar methotrexate and radioactivity levels correlated closely. Three patients with a normal CSF flow study are alive at 15+, 7.5+, and 3.9+ months from treatment. Of 12 with abnormal CSF flow studies, 11 are dead a median of 2 months from diagnosis. Two patients had diffusely delayed flow studies and both developed methotrexate leukoencephalopathy. CSF flow studies using 111In-DTPA reliably predict distribution of intrathecal methotrexate. Abnormal flow studies correlate with structural abnormalities, are an unfavorable prognostic factor, and may predict intrathecal chemotherapy toxicity.

Labeling efficiency and stomach concentration in methylene diphosphonate bone imaging.

When Tc-99m-labeled methylene diphosphonate was used 4.75 hr after reconstitution, stomach concentration was seen in the majority of patients. The number of patients with stomach concentration increases with time and is associated with the increasing amount of product breakdown. The reconstituted labeled MDP should not be used after 4-5 hr if stomach concentration is to be avoided.

Scintigraphic features of primary sacral tumors.

The bone scan features of different types of sacral tumors in 16 patients were assessed. Four out of five patients with chordoma, the most common sacral tumor, demonstrated either reduced uptake or normal distribution of isotope at the site of this midline tumor. Plasmacytoma, which is not usually central, also caused reduced uptake on the bone scan. Ewing's sarcoma gave no consistent pattern. All other tumors caused increased uptake except for one unusual case of osteogenic sarcoma. Bone scintigraphy can be very useful in the assessment of sacral tumors. A midline sacral tumor that is cold on the bone scan is very likely to be a chordoma.

Technetium-99m albumin scintigraphy in the diagnosis of protein-losing enteropathy.

While several studies have documented protein losing enteropathy by measuring the excretion of intravenously administered 131I- or 51Cr-labeled albumin, the efficacy of 99mTc-labeled albumin in detecting protein loss in the bowel has not been described. We report here a case of severe protein-losing enteropathy demonstrated by abnormal excretion of 99mTc albumin into the bowel.

Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities.

Iodine-131-3F8, a murine IgG3 monoclonal antibody specific for ganglioside GD2 was evaluated by radioimmunoscintigraphy in 42 patients with neuroblastoma. Comparison was made with 131I-metaiodobenzylguanidine (MIBG), 99mTc-methylene diphosphonate (MDP) bone scans, as well as computed axial tomography (CT) or magnetic resonance imaging (MRI). Iodine-131-3F8 detected more abnormal sites (283) than [131I] MIBG (138) or 99mTc-MDP (69), especially in patients with extensive disease. In 20 patients with soft-tissue tumors demonstrated by CT/MRI, 131I-3F8 detected the disease in 18. Upon surgical resection, two tumors interpreted as negative with 131I-3F8 imaging revealed ganglioneuroma, one showing microscopic foci of neuroblastoma. In contrast, 131I-3F8 imaging identified tumors that were confirmed histologically as neuroblastomas. In 26 patients with evidence of marrow disease by antibody scans, 14/26 had confirmation by iliac crest marrow aspirate/biopsy examinations. We conclude that 131I-3F8 scintigraphy has clinical utility in the management of patients with neuroblastoma by improving the sensitivity of tumor detection.

Image registration of SPECT and CT images using an external fiduciary band and three-dimensional surface fitting in metastatic thyroid cancer.

Image registration of 131I SPECT with CT scans was performed in a patient with metastatic thyroid carcinoma using an external fiduciary band and a three-dimensional surface-fitting algorithim. Areas of metastatic disease taking up 131I were accurately localized to the liver, lungs and vertebral bodies; providing information that could not be obtained by planar or SPECT images alone. Based on these findings, further invasive diagnostic procedures were not performed, therefore considerably altering management in this patient. This approach to image registration has immediate clinical utility in the registration and interpretation of SPECT studies with corresponding CT or MRI scans.

Lymphoscintigraphy and sentinel node localization in breast cancer patients: a comparison between 1-day and 2-day protocols.

UNLABELLED: The purpose of this study was to compare the results of isotope injection the morning of surgery (1-d protocol) with isotope injection the day before surgery (2-d protocol) in patients having sentinel lymph node (SLN) biopsy for breast cancer. METHODS: The 1-d (protocol 1) and 2-d (protocol 2) protocols included 514 and 152 patients, respectively, treated contemporaneously by surgeons experienced with the SLN biopsy technique. All had preoperative lymphoscintigraphy (LSG) and SLN biopsy using both blue dye and (99m)Tc-sulfur colloid. All patients had a single-site intradermal injection of unfiltered (99m)Tc-sulfur colloid in 0.05 mL normal saline: 3.7 MBq (0.1 mCi) on the morning of surgery for protocol 1 and 18.5 MBq (0.5 mCi) on the afternoon before surgery for protocol 2. RESULTS: The patients in protocols 1 and 2 were comparable in terms of age, tumor size, tumor location, histologic type, node positivity, and frequency of a previous surgical biopsy. Comparing protocols 1 and 2, early (30 min) LSG images found the SLN equally often (69% vs. 68%). Isotope identified the SLN equally often at surgery (93% vs. 97%) as did isotope plus dye (98% vs. 99%). A comparable number of SLNs was found (2.5 vs. 2.8 per axilla), and the concordance between isotope and dye in the SLN was also comparable (97% vs. 95%). Late LSG images (at 2 h, possible only for protocol 2) identified the SLN in significantly more patients compared with early images (86% vs. 68%). CONCLUSION: With unfiltered (99m)Tc-sulfur colloid injected intradermally, the results of SLN biopsy under the 1-d and 2-d protocols are virtually identical. A 2-d protocol allows increased efficiency in scheduling, both for nuclear medicine physicians and for the operating room, with no compromise in the effectiveness of SLN mapping.