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1.
Cancer Imaging ; 9: 59-62, 2009 Sep 29.
Article in English | MEDLINE | ID: mdl-19933018

ABSTRACT

Localizing positron emission tomography (PET)/computed tomography (CT) findings in heavily scarred surgical fields can be challenging. A high energy gamma probe (PET probe) can be used to guide surgery in those difficult areas. We describe our experience localizing and removing fluorodeoxyglucose (FDG) avid lesions in different body areas. Between 2004 and 2007, we used the PET probe to localize and remove 12 lesions from 9 patients. The lesions were removed confirming ex vivo and tumor bed FDG activity. Five patients had lesions in previously operated and sometimes radiated fields. One patient had FDG avid spots in the retroperitoneum. Two lymphoma patients had been previously treated and had new FDG avid spots in a background of scarred nodes. The last patient had a core biopsy suspicious for lymphoma but a repeat CT was non-specific. One patient with gastric cancer patient, two patients with melanoma patients and two patients with breast cancer had 10 metastatic lesions easily identified and removed. After a median follow-up of 14 months all five patients are alive. The two patients with lymphoma had their FDG avid lymph nodes easily identified and biopsied. In one patient with melanoma and one patient with suspected lymphoma, the preoperative scan revealed no FDG avid lesions. The PET probe confirmed this finding in the operating room. Clinical applications of PET probe guided surgery include restaging for previously treated lymphoma patients, localization and resection of metastatic FDG avid nodules especially in previously operated or radiated fields and biopsy of PET findings difficult to localize.


Subject(s)
Fluorodeoxyglucose F18 , Neoplasms/diagnostic imaging , Positron-Emission Tomography/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/surgery , Female , Humans , Lymphoma/diagnostic imaging , Lymphoma/surgery , Melanoma/diagnostic imaging , Melanoma/surgery , Neoplasms/surgery , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery
2.
Q J Nucl Med ; 45(1): 91-9, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11456381

ABSTRACT

Various radioisotopes conjugated to pyrophosphate analogues have been developed for systemic metabolic radiotherapy. Samarium-153-EDTMP is a 1:1 complex of radioactive Samarium-153 and a Tetraphosphonate [ethylenediamine-tetramethylene phosphonic acid (EDTMP)]. Samarium Sm-153-EDTMP has a high affinity for skeletal tissue and concentrates by chemiabsorption in areas of enhanced metabolic activity, where it associates with the hydroxyapatite crystal. Samarium-153 Lexidronam [Quadramet (R)] has been approved for routine use by the FDA. This agent offers several advantages over other agents used for palliating bone pain. Due to its half-life of 46 hours and its beta emissions, a high dose rate can be delivered to regions adjacent to enhanced osteoblastic activity over a short period of time with little residual long term activity being left in the bone marrow. This paper summarizes both animal studies and clinical studies performed with this agent. Special emphasis will be given to the pivotal Phase-III clinical studies and subsequent studies performed since its approval by the FDA. Special considerations regarding appropriate selection of patients, preparation, follow-up of patients and adjustments to the usual recommended dose [1 mCi/kg (35 Mbq/kg)] will be discussed. Current and future treatment options utilizing Sm-153-EDTMP with other pharmaceuticals appear promising and will substantially extend its use into new areas. In addition, because it also emits a 103 keV gamma ray which makes it suitable for imaging and assessment of biodistribution, dosimetric applications are possible in the future.


Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Bone Neoplasms/radiotherapy , Bone Neoplasms/secondary , Organometallic Compounds/therapeutic use , Organophosphorus Compounds/therapeutic use , Pain, Intractable/radiotherapy , Palliative Care , Animals , Dogs , Female , Humans , Male , Rats , Samarium/therapeutic use
3.
J Nucl Med ; 42(6): 895-906, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11390554

ABSTRACT

Bone metastasis is a common sequella of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Currently, the treatment of bone pain remains palliative at best with systemic therapy (analgesics, hormones, chemotherapy, steroids, and bisphosphonates) as well as local treatments (such as surgery, nerve blocks, and external beam radiation). However, many of these treatments are limited in their efficacy or duration and have significant side effects that seriously limit the cancer patient's quality of life. Various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studies, improved survival. Additional radiopharmaceuticals are under investigation and appear promising. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment.


Subject(s)
Bone Neoplasms/secondary , Pain/radiotherapy , Analgesics/therapeutic use , Animals , Bone Neoplasms/complications , Humans , Organometallic Compounds , Organophosphorus Compounds , Pain/drug therapy , Pain/etiology , Phosphates/therapeutic use , Phosphorus Radioisotopes/therapeutic use , Radioisotopes , Radiopharmaceuticals/therapeutic use , Samarium , Strontium/therapeutic use , Strontium Radioisotopes/therapeutic use
4.
Cancer ; 88(12 Suppl): 2934-9, 2000 Jun 15.
Article in English | MEDLINE | ID: mdl-10898337

ABSTRACT

BACKGROUND: In patients with bone pain due to metastatic disease, intravenous systemic radioisotope therapy may be a useful adjunct to other methods for palliating pain. METHODS: Various studies have been performed utilizing a short-lived radioisotope conjugated to a tetraphosphonate (samarium 153 lexidronam) both as an open label and as a double blinded, placebo-controlled study. Patients with varying tumor types including those of the prostate, breast, lung, and other sites were studied. Two dose levels were used (0.5 millicuries (mCi)/kg and 1.0 mCi/kg) with patients monitored for 16 weeks for efficacy (pain scores, opiod analgesic score, and quality of life) parameters and adverse events. RESULTS: All 3 studies showed that at the 1.0 mCi/kg dose level statistically significant improvement over placebo was observed by 4 weeks with relief of pain noted in many patients by 1 week. The only significant adverse event was transient myelosuppression with a nadir at 4-6 weeks and recovery by 8 weeks. Less than 10% of patients had National Cancer Institute Common Toxicity Criteria Grade III/IV bone marrow toxicity recorded. CONCLUSIONS: Systemic metabolic radiotherapy with samarium 153 lexidronam appears to be a safe and efficacious method for treating patients with bone pain. The shorter radioisotope half-life allows for a high dose rate to be delivered over a short period, which may have certain biologic benefits.


Subject(s)
Bone Neoplasms/radiotherapy , Bone Neoplasms/secondary , Pain Management , Palliative Care , Samarium/therapeutic use , Bone Neoplasms/physiopathology , Clinical Trials as Topic , Humans , Samarium/adverse effects , Samarium/pharmacokinetics
5.
Otolaryngol Head Neck Surg ; 122(3): 358-62, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10699810

ABSTRACT

Paragangliomas are neuroendocrine tumors located primarily in the head and neck region, but they can also occur at other sites. Confirming the preoperative diagnosis and detecting synchronous tumors may be difficult in some patients. Octreotide is a somatostatin analog that, when coupled to a radioisotope, produces a scintigraphic image of tumors expressing somatostatin type 2 receptors. Paragangliomas, like many neuroendocrine tumors, have been found to have a high density of somatostatin type 2 receptors on the cell surface. This study compared the results of preoperative octreotide scintigraphy with the histopathology in 21 patients who underwent surgery for presumed head and neck paragangliomas. Octreotide scan findings were positive in 16 patients with paragangliomas and negative in 3 patients with other pathology. One false-positive and 1 false-negative result were obtained. Thus, this test had an accuracy of 90%, a sensitivity of 94%, and a specificity of 75%. Previously unidentified synchronous tumors were identified in 5 patients. On the basis of this series of patients, octreotide scintigraphy appears to be a reliable test to detect paragangliomas and may be quite helpful in preoperative planning.


Subject(s)
Neoplasms, Multiple Primary/diagnostic imaging , Otorhinolaryngologic Neoplasms/diagnostic imaging , Paraganglioma/diagnostic imaging , Somatostatin/analogs & derivatives , Tomography, Emission-Computed, Single-Photon , Female , Humans , Male , Otorhinolaryngologic Neoplasms/chemistry , Otorhinolaryngologic Neoplasms/surgery , Paraganglioma/chemistry , Paraganglioma/surgery , Predictive Value of Tests , Receptors, Somatostatin/analysis
6.
Cancer Invest ; 17(5): 322-34, 1999.
Article in English | MEDLINE | ID: mdl-10370360

ABSTRACT

Radioimmunoscintigraphy (RIS) is coming into its own as an imaging modality in clinical oncology. Early experience with indium-111-labeled intact murine monoclonal antibodies (MoAbs) in colorectal cancer suggested that RIS images hepatic metastases poorly. Moreover, an antimurine immune response was frequently provoked, precluding multiple follow-up RIS studies in individual patients due to reticuloendothelial sequestration of the radioimmunoconjugate before tumor targeting could occur. Recent trials of technetium-99m-labeled antibody fragments and human MoAbs have demonstrated significant improvement in imaging efficacy, and repeated or serial imaging is possible because of the absence of associated immunogenicity. RIS is demonstrably more sensitive than conventional diagnostic modalities (CDM) such as computed tomography (CT) for detection of extrahepatic abdominal and pelvic colorectal carcinoma and is complementary to CDM in imaging liver metastases. In a surgical decision-making analysis comparing CT, RIS (IMMU-4 99mTc-Fab'; CEA-Scan), and CT plus RIS in patients with recurrent or metastatic colorectal cancer, CT plus RIS improved correct prediction of resectability by 40% and correct prediction of unresectability by 100% compared with CT alone. At the present time, RIS used in combination with CDM contributes an incremental improvement in diagnostic accuracy in colorectal cancer patients with known or suspected recurrent disease. Basic and clinical research currently in progress promises to yield agents and methods that provide rapid high-resolution imaging, high tumor-to-background ratios in all organs at risk for tumor recurrence or metastasis, negligible immunogenicity and toxicity, and a significant further improvement in the accuracy of clinical decision making in oncology patients.


Subject(s)
Colorectal Neoplasms/diagnostic imaging , Radioimmunodetection , Antibodies, Monoclonal , Colorectal Neoplasms/pathology , Epitopes , Humans , Immunoconjugates , Immunoglobulin Fab Fragments , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Neoplasm Recurrence, Local/diagnostic imaging
7.
Ann Surg Oncol ; 6(8): 746-55, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10622502

ABSTRACT

BACKGROUND: There are few clinical data on technical limitations and radiocolloid kinetics related to sentinel lymph node (SLN) biopsy for breast cancer. METHODS: In 70 clinical node-negative patients, unfiltered 99mTc sulfur-colloid was injected peritumorally and cutaneous hot spots were mapped with a gamma probe. SLN biopsy was performed followed by axillary lymph node dissection. Missed radioactive nodes (nodes not under hot spots) were removed from axillary lymph node dissection specimens and submitted separately. RESULTS: At least one hot spot was mapped in 69 patients (98%) and SLNs were retrieved in 62 (89%). No radiolabeled nodes were found in five (7%) and only nodes not under hot spots were retrieved in three patients (4%). Residual nodes not under hot spots were retrieved in 17 patients (24%) in whom at least one SLN specimen had been found. Diffuse radioactivity around the radiocolloid injection site impeded identification of all radiolabeled nodes during SLN biopsy, and was responsible for one of two false negatives (20 node-positive patients; false-negative rate 10%). Hot spot radioactivity, number of radiolabeled nodes, and nodal radioactivity did not change with time interval from radiocolloid injection to surgery (0.75-6.25 hours). CONCLUSIONS: Although SLN localization rate is high, intraparenchymal injection may predispose to failure of radiocolloid migration, failure to identify SLNs because of high radiation background, and false-negative outcomes. Alternative routes of radiocolloid administration should be explored.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Radiopharmaceuticals , Technetium Tc 99m Sulfur Colloid , Adult , Aged , Aged, 80 and over , Biopsy , Breast Neoplasms/metabolism , False Negative Reactions , Humans , Lymphatic Metastasis , Middle Aged , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Technetium Tc 99m Sulfur Colloid/pharmacokinetics
8.
Dis Colon Rectum ; 41(8): 953-62, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9715149

ABSTRACT

PURPOSE: The study contained herein was undertaken to evaluate the accuracy of radiolabeled human monoclonal antibody, 88BV59H21-2V67-66 (88BV59 or HumaSPECT-Tc), in predicting disease resectability in presurgical subjects with recurrent, metastatic, or occult colorectal carcinoma. METHODS: A total of 219 patients with disease visualized on computed tomographic scan (recurrent or metastatic disease) or with negative or equivocal computed tomographic scan and rising carcinoembryonic antigen serum levels (occult group) received technetium Tc99m-labeled 88BV59 intravenously. Planar and single photon emission computed tomograhic images were obtained 14 to 20 hours postinfusion, before surgery. The ability of computed tomographic and HumaSPECT-Tc imaging to define the extent of disease and to predict resectability was evaluated based on surgical and histopathologic results. RESULTS: In patients with recurrent or metastatic disease (170 evaluable patients), the accuracy of predicting nonresectability of disease was significantly greater (P < 0.001) for HumaSPECT-Tc than for computed tomography (60 vs 29 percent). Computed tomography understaged 41 percent of patients believed to have resectable disease compared with 27 percent for HumaSPECT-Tc (P < 0.001). In occult disease patients (29 computed tomographic and 28 HumaSPECT-Tc evaluable patients), the overall accuracy of predicting resectability/nonresectability was 6 percent for HumaSPECT-Tc compared with 24 percent from computed tomography. Administration of HumaSPECT-Tc had no effect on monoclonal antibody-based in vitro diagnostic assays. Only a single patient demonstrated an anti-antibody response (90 ng/ml) at nine weeks postinfusion. CONCLUSION: HumaSPECT-Tc was more accurate than computed tomography in determining disease resectability in patients with metastatic, recurrent, or occult cancer. The addition of HumaSPECT-Tc imaging can play a significant role in patient management decisions.


Subject(s)
Antibodies, Monoclonal , Colorectal Neoplasms/diagnostic imaging , Radioimmunodetection/methods , Adult , Antibodies, Monoclonal/adverse effects , Colorectal Neoplasms/secondary , Colorectal Neoplasms/surgery , Female , Humans , Male , Neoplasm Recurrence, Local , Safety , Technetium , Tomography, Emission-Computed, Single-Photon , Whole-Body Counting
9.
J Nucl Med ; 39(8): 1388-93, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9708514

ABSTRACT

METHODS: Thirty-two patients with clinical node-negative breast cancer underwent sentinel node localization study as part of a National Cancer Institute-sponsored multicenter trial. Anatomical and histopathologic characteristics of sentinel lymph node (SLN) and a kinetic analysis of nodal uptake were studied. Patients were injected with 1 mCi/4 ml unfiltered 99mTc-sulfur colloid in four divided doses around the palpable lesion or immediately adjacent to the excision cavity if prior biopsy was performed. SLN biopsy was performed 1.5-6 hr (mean = 3 hr) postinjection. Intraoperative localization was performed using a gamma probe. All patients underwent complete axillary dissection. RESULTS: SLN was identified in 30 of 32 (94%) patients. There were no false-negative SLN biopsies. CONCLUSION: This study supports the clinical validity of SLN biopsy in breast cancer and confirms that, unlike the blue dye technique, the learning curve with unfiltered 99mTc-sulfur colloid and the gamma detection probe is short, and SLN localization is achievable in over 90% of cases by surgeons with modest experience. The use of unfiltered 99mTc-sulfur colloid (larger particle size) with larger injected volume permits effective localization of SLNs.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/secondary , Lymph Nodes/diagnostic imaging , Radiopharmaceuticals , Technetium Tc 99m Sulfur Colloid , Adult , Aged , Axilla , Biopsy , Female , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Prospective Studies , Radionuclide Imaging
11.
J Clin Oncol ; 16(5): 1777-87, 1998 May.
Article in English | MEDLINE | ID: mdl-9586891

ABSTRACT

PURPOSE: To assess the performance and potential clinical impact of a totally human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in 202 assessable presurgical patients with recurrent, metastatic, or occult colorectal cancer. METHODS: 88BV59, labeled with technetium Tc 99m (99mTc) (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical and pathologic verification of tumor were used as the standard against which the performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were evaluated. RESULTS: All patients entered onto the recurrent disease study had at least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT-positive patients was 87%. The specificity of HumaSPECT-Tc was 57% compared with 17% for CT and the difference was statistically significant (P < .001). The diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved the accuracy of the identification of resectable and nonresectable disease over that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001) reduction versus CT in terms of the proportion of patients understaged (27% v 41%) and overstaged (4% v 26%). In patients with occult disease (increasing carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT), HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT-Tc images provided additional clinical data that would have affected patient management decisions in 40 of 202 (19.8%) patients. In 365 patients who received 88BV59, only a single detectable human anti-human antibody (HAHA) response (90 ng/mL) at 9 weeks postinfusion was observed. CONCLUSION: HumaSPECT-Tc can provide important and accurate information about the presence and location of disease in patients with a high clinical suspicion of metastatic or recurrent colorectal cancer and either positive (known disease) or negative (occult disease) CT scans.


Subject(s)
Colorectal Neoplasms/diagnostic imaging , Radioimmunodetection , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Humans , Middle Aged , Neoplasm Metastasis/diagnostic imaging , Neoplasm Recurrence, Local/diagnostic imaging , Sensitivity and Specificity , Technetium/adverse effects , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
12.
J Clin Oncol ; 16(4): 1574-81, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9552068

ABSTRACT

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.


Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Bone Neoplasms/secondary , Organometallic Compounds/therapeutic use , Organophosphorus Compounds/therapeutic use , Pain, Intractable/drug therapy , Palliative Care , Adult , Aged , Aged, 80 and over , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/adverse effects , Bone Neoplasms/complications , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Middle Aged , Organometallic Compounds/administration & dosage , Organometallic Compounds/adverse effects , Organophosphorus Compounds/administration & dosage , Organophosphorus Compounds/adverse effects , Pain Measurement , Pain, Intractable/etiology
13.
J Nucl Med ; 39(2): 243-5, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9476928

ABSTRACT

Somatostatin receptor expression, which was not a previously described marker for Hürthle cell cancer of the thyroid, was demonstrated by in vivo imaging with (111)In-pentetreotide in three patients. This phenomenon not only adds another imaging technique to the nuclear medicine armamentarium for detecting recurrent and metastatic cancer in patients with Hürthle cell cancer but also opens up an alternative therapeutic avenue with somatostatin analogs or their radiolabeled compounds.


Subject(s)
Adenoma, Oxyphilic/metabolism , Receptors, Somatostatin/analysis , Thyroid Neoplasms/metabolism , Adenoma, Oxyphilic/diagnostic imaging , Aged , Humans , Indium Radioisotopes , Male , Middle Aged , Octreotide/analogs & derivatives , Pentetic Acid/analogs & derivatives , Radionuclide Imaging , Radiopharmaceuticals , Thyroid Neoplasms/diagnostic imaging
14.
AJNR Am J Neuroradiol ; 18(6): 1073-80, 1997.
Article in English | MEDLINE | ID: mdl-9194434

ABSTRACT

PURPOSE: To evaluate indium 111 octreotide scintigraphy for the detection of suspected neuroendocrine lesions of the head and neck. METHODS: After receiving 6 mCi of 111In octreotide, 22 patients with suspected lesions of the head and neck were examined with both planar and single-photon emission CT (SPECT). Static images, obtained at 4 hours, included the head/neck, chest, abdomen, and pelvis. Additional SPECT images were obtained at 4 or 24 hours. Studies were compared with available conventional radiologic examinations (12 CT, 11 MR, and three angiographic studies) as well as with clinical and pathologic findings. RESULTS: Eighteen of the 22 patients had abnormal findings at scintigraphy. Eleven paragangliomas were seen in 10 patients, metastatic medullary thyroid carcinoma in three patients, thyroid adenoma in two patients, and Merkel cell tumor, carcinoid, and plasmacytoma in one patient each. Surgical confirmation was available in 13 patients. The smallest lesion detected was 1.5 cm. There was one false-positive and one false-negative examination. CONCLUSION: 111In octreotide scintigraphy is a useful imaging tool for the detection of primary and metastatic neuroendocrine tumors of the head and neck that are larger than 1.5 cm. This technique enables distinction of glomus tumors from other masses (such as neuromas) and can be used in the postoperative setting to distinguish scar from recurrent paraganglioma. Since it is an examination of the entire body, it has great utility for detecting multicentric paraganglioma and for screening patients with familial paraganglioma.


Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Neuroendocrine Tumors/diagnostic imaging , Somatostatin/analogs & derivatives , Tomography, Emission-Computed, Single-Photon , Adult , Aged , Female , Head and Neck Neoplasms/secondary , Humans , Indium Radioisotopes , Male , Middle Aged , Neuroendocrine Tumors/secondary , Sensitivity and Specificity
16.
ASAIO J ; 42(6): 1010-8, 1996.
Article in English | MEDLINE | ID: mdl-8959277

ABSTRACT

The effect of an arterial filter on visceral emboli was quantified with autologous indium-111 labeled platelets (INPLT) during cardiopulmonary bypass (CPB) in Yorkshire pigs. Biodistribution of INPLT was determined in 12 control pigs (30-35 kg, unoperated control [n = 6] and sham operated control [n = 6]). CPB was carried out with (n = 6) and without (n = 6) an arterial filter in 12 pigs at a flow rate of 2.5-3.5 L/min. Platelets labeled with In-111 tropolone (650-780 microCi) were injected intravenously 24 hr before CPB. All pigs were systemically heparinized (activated coagulation time > 400 sec); CPB was instituted with a roller pump, an extraluminal blood flow oxygenator (Bentley Univox, 1.8 m2), and an arterial filter (0.25 m2) and continued for 3 hr. Platelet kinetics, pooling, and counts were monitored by a Geiger probe and a Coulter counter. The thrombi in the oxygenator and arterial filter and emboli in viscera and brain were imaged with a gamma camera and measured with an ion chamber and gamma counter. Percentage of INPLT (mean +/- SD) in organs, tissues, and components of the circuit in four groups of pigs was calculated. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140: control) of porcine platelets was carried out with blood samples taken before, during, and after CPB for estimation of circulating platelet aggregates and platelet microparticles. Pulmonary, renal, cardiac, and cerebral emboli in pigs undergoing CPB with and without a filter were similar (p < 0.1). The amount of filter adherent thrombi was small (0.04 +/- 0.01%); oxygenator adherent thrombus in both groups was similar (p < 0.1). Emboli were found in the cerebral medulla, hippocampus, and posterior cerebral cortex in both groups. During CPB, the arterial filter functioned minimally as a trap for platelet thrombi detached from the oxygenator and circulating emboli. Flow cytometry of blood demonstrated the shift of equilibria from single platelets to platelet aggregates and microparticles during CPB and their gradual reversal to single platelets after CPB; the loosely adherent emboli disaggregated and further shifted these equilibria to single platelets and smaller aggregates, probably through the action of endogenous nitric oxide and prostacyclin. The emboli were trapped in organs and tissues and microparticles were sequestered by the reticuloendothelial system.


Subject(s)
Cardiopulmonary Bypass/adverse effects , Extracorporeal Membrane Oxygenation/adverse effects , Thromboembolism/physiopathology , Animals , Biocompatible Materials/metabolism , Biocompatible Materials/therapeutic use , Blood Platelets/cytology , Disease Models, Animal , Flow Cytometry , Indium , Isotope Labeling , Oxygenators/standards , Swine , Thromboembolism/diagnosis , Tropolone/chemistry
17.
ASAIO J ; 42(5): M661-6, 1996.
Article in English | MEDLINE | ID: mdl-8944963

ABSTRACT

Nitric oxide generation by L-arginine (2 mg/kg/min) infusion during cardiopulmonary bypass (CPB) increases blood flow to all organs and reduces cytokine induced organ damage by reducing the level of marginating neutrophils (Ns). The N-trapping in the oxygenator (OX), arterial filter (AF), cardiotomy reservoir (CR), and N-margination were quantified with indium 111 labeled autologous neutrophils (INN) in nine groups of 40 Yorkshire pigs (30-35 kg). Cardiopulmonary bypass (180 min or 90 min CPB, 90 min reperfusion) was carried out at 2.5-3.5 L/min and at two temperatures (18 degrees C, 28 degrees C). The INN (650-780 microCi) was administered intravenously 15 mins before CPB. All pigs received heparin systemically (activated coagulation time > 400 secs); CPB was instituted with a roller pump, OX (Univox 1.8 m2), AF (0.25 m2), and CR (BCR-3500, Bentley Lab, Irvine, CA). The INN distribution in the device (OX, AF, CR) and organs was imaged with a gamma camera and measured with an ion chamber and a gamma counter. The LA infusion decreased N-trapping, estimated as the percent of injected INN (mean +/- standard deviation), in OX from control (2.7 +/- 2.02)% to (0.94 +/- 0.29)%, and margination in lung from control (48 +/- 4)% to minimal levels (23 +/- 2)% (p < 0.01). In the CPB reperfusion group, a beneficial effect was observed at LA low dose and toxicity of higher N-margination at 15 mg/ kg/min. Neither CPB temperature nor Leumedin affected N-margination significantly.


Subject(s)
Arginine/pharmacology , Cardiopulmonary Bypass/methods , Neutrophils/drug effects , Animals , Arginine/administration & dosage , Brain/cytology , Cardiopulmonary Bypass/adverse effects , Cell Adhesion , Cell Movement/drug effects , Hypothermia, Induced , Indium Radioisotopes , Neutropenia/etiology , Neutropenia/prevention & control , Neutrophils/physiology , Nitric Oxide/blood , Swine
18.
Cancer ; 77(11): 2286-93, 1996 Jun 01.
Article in English | MEDLINE | ID: mdl-8635097

ABSTRACT

BACKGROUND: Accurate evaluation of patients with ovarian carcinoma who have completed primary therapy often requires surgical exploration. Radioimmunoscintigraphy (RIS) represents an evolving technique that may allow noninvasive detection and localization of persistent or recurrent disease in these patients. METHODS: Our prospective, blinded study enrolled patients with normal CA 125 levels and no clinical evidence of disease after primary cytoreductive surgery and cytotoxic chemotherapy for ovarian carcinoma. Each patient underwent RIS using Indium-satumomab pendetide (labeled antibody B72.3 to the tumor-associated antigen TAG-72) and abdominal/pelvic computed tomography (CT) prior to reassessment laparotomy. RESULTS: Twenty patients were enrolled from January 1994 to January 1995. Two patients with negative RIS scans refused reassessment laparotomy and were without evidence of disease > 15 months from the study. Twelve of the remaining 18 patients (66.7%) had histologically proven disease at reassessment laparotomy. RIS images indicated the presence of disease in all 12 patients, whereas CT scans detected disease in only 2 patients. In three of five patients, biopsy-proven microscopic disease (no gross disease at the time of laparotomy) was found only in specimens obtained by RIS-directed biopsies. RIS was superior to CT in sensitivity (100% vs. 16.7%), accuracy (72% vs. 33%), and negative predictive value (100% vs. 28.6%) (P < 0.005). CONCLUSIONS: Routine use of CT is of limited value in the assessment of ovarian carcinoma patients with negative physical examinations and normal CA 125 levels. With its high level of sensitivity and negative predictive value, RIS may play a role in the detection of persistent disease in this population and aid in the classification of patients into three distinct groups: those with gross residual disease, small volume or microscopic disease, and no disease. Separation of this heterogenous group without surgery may help guide subsequent consolidation therapy. However, attaining a high level accuracy with RIS, depends on optimizing the method of image acquisition, the timing of scans, and the reconstruction of data.


Subject(s)
Antibodies, Monoclonal , Carcinoma/diagnostic imaging , Indium Radioisotopes , Oligopeptides , Ovarian Neoplasms/diagnostic imaging , Pentetic Acid/analogs & derivatives , Radioimmunodetection , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Carcinoma/drug therapy , Carcinoma/pathology , Carcinoma/surgery , Cisplatin/administration & dosage , Combined Modality Therapy , Female , Humans , Image Processing, Computer-Assisted , Laparotomy , Mice , Middle Aged , Neoplasm, Residual , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Paclitaxel/administration & dosage , Predictive Value of Tests , Prospective Studies , Remission Induction , Sensitivity and Specificity , Single-Blind Method
19.
Cancer Res ; 55(23 Suppl): 5774s-5776s, 1995 Dec 01.
Article in English | MEDLINE | ID: mdl-7493345

ABSTRACT

Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response.


Subject(s)
Antibodies, Monoclonal , Carcinoma/diagnostic imaging , Colorectal Neoplasms/diagnostic imaging , Radioimmunodetection , Technetium , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
20.
Q J Nucl Med ; 39(3): 169-86, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7552941

ABSTRACT

The Human Immunodeficiency Virus (HIV) is the causative agent for the expanding epidemic of the Acquired Immunodeficiency Syndrome (AIDS). Sixteen million individuals were estimated to be infected worldwide with HIV by the World Health Organization in 1995, with over 10 million in Africa and one million in the USA. As the HIV cost in dollars and lives continues to rise it will become more important to understand AIDS and to foresee the potential role of nuclear medicine in HIV diseases. Nuclear medicine may have a role in the assessment of immune function, including the ability to predict if individuals can avoid progression to HIV+status, if pre-AIDS to AIDS conversion can be prevented, and if an individual's immune status requires addition of prophylaxis. Also it can be used for disease detection at an early stage and determination of the extent of disease. It is especially useful to assist clinicians in optimizing therapy and assessing its efficacy. In the future new radiopharmaceuticals for detecting a specific infections and tumors will be needed. This will require collaborative efforts with basic scientists and clinicians working hand in hand to address specific issues related to AIDS.


Subject(s)
Acquired Immunodeficiency Syndrome/diagnostic imaging , Acquired Immunodeficiency Syndrome/complications , Humans , Lung Diseases/complications , Lung Diseases/diagnostic imaging , Radionuclide Imaging
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