Immunoscintigraphy In Patients Research Articles

Sensitivity and Prognostic Value of Positron Emission Tomography with F-18-Fluorodeoxyglucose and Sensitivity of Immunoscintigraphy in Patients with Medullary Thyroid Carcinoma Treated with Anticarcinoembryonic Antigen-Targeted Radioimmunotherapy

Sensitivity and Prognostic Value of Positron Emission Tomography with F-18-Fluorodeoxyglucose and Sensitivity of Immunoscintigraphy in Patients with Medullary Thyroid Carcinoma Treated with Anticarcinoembryonic Antigen-Targeted Radioimmunotherapy

Sensitivity and Prognostic Value of Positron Emission Tomography with F-18-Fluorodeoxyglucose and Sensitivity of Immunoscintigraphy in Patients with Medullary Thyroid Carcinoma Treated with Anticarcinoembryonic Antigen-Targeted Radioimmunotherapy

Patients with progressive medullary thyroid carcinoma (MTC) undergo multiple imaging procedures for diagnosis of relapse and staging. Our objective was to assess the sensitivity and prognostic value of 18F-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT), and the imaging sensitivity of pretargeted iodine-131-radioimmunotherapy (RIT) in patients with progressive MTC. We performed a prospective multicenter study in high-risk patients with rapidly progressing MTC enrolled in a phase-II pretargeted RIT study, as documented by short serum calcitonin (Ct) or carcinoembryonic antigen (CEA) doubling time (DT). INTERVENTIONS/MAIN OUTCOME MEASURES: Patients underwent neck-thoracic-abdominal CT, spine and pelvic magnetic resonance imaging, whole-body post-RIT immunoscintigraphy (IS) with iodine-131, and whole-body 18F-FDG-PET/CT imaging. Imaging sensitivity and the correlation between FDG uptake and biomarkers DT were evaluated. A total of 33 patients with mean CEA and Ct DTs of 1.90 yr (range 0.21-8.50) and 1.52 yr (range 0.09-6.01), respectively, were evaluated. Sensitivity of FDG-PET/CT was 83% for neck, 85% for mediastinal, 75% for lung, 60% for liver, and 67% for bone metastases; overall sensitivity was 76%. Median standardized uptake value (SUVmax) was 5.23 (2.06-13.90). SUVmax correlated significantly with Ct DT (P = 0.011) and minimal DT (minimal value between CEA DT and Ct DT) (P = 0.027). Overall sensitivity of post-RIT IS, CT, and bone magnetic resonance imaging were 94, 74, and 85%, respectively. These results demonstrate the value of FDG-PET/CT for staging of patients with progressive MTC, especially in the neck and mediastinum, with possible prognostication by SUV quantification. Post-RIT IS was the most sensitive of the imaging modalities studied prospectively.

CD105 is important for angiogenesis: evidence and potential applications.

Angiogenesis is the propelling force for tumor growth and metastasis, and antiangiogenic therapy represents one of the most promising modalities for cancer treatment. CD105 (endoglin) is a proliferation-associated and hypoxia-inducible protein abundantly expressed in angiogenic endothelial cells (EC). It is a receptor for transforming growth factor (TGF) -beta1 and -beta3 and modulates TGF-beta signaling by interacting with TGF-beta receptors I and/or II. Immunohistochemistry studies have revealed that CD105 is strongly expressed in blood vessels of tumor tissues. Intratumoral microvessel density (MVD) determined using antibodies to CD105 has been found to be an independent prognostic indicator, wherein increased MVD correlates with shorter survival. CD105 is able to be shed into the circulation, with elevated levels detected in patients with various types of cancer and positively correlated with tumor metastasis. Tangible evidence of its proangiogenic role comes from knockout studies in which CD105 null mice die in utero as a result of impaired angiogenesis in the yolk sac and heart defects. The potential usefulness of CD105 for tumor imaging has been evaluated in tumor-bearing mice and dogs that have shown the rapid accumulation of radiolabeled anti-CD105 monoclonal antibody in the tumors with a high tumor-to-background ratio. The anti-CD105 antibody conjugated with immunotoxins and immunoradioisotopes efficiently suppressed/abrogated tumor growth in murine models bearing breast and colon carcinoma without any significant systemic side effects. Immunoscintigraphy in patients with renal cell carcinomas has shown specific localization of 99Tcm-labeled CD105 mab in tumor endothelial cells. Thus, CD105 is a promising vascular target that can be used for tumor imaging, prognosis, and bears therapeutic potential in patients with solid tumors and other angiogenic diseases.

Pretargeted immunoscintigraphy in patients with medullary thyroid carcinoma

To evaluate the use of pretargeted immunoscintigraphy (ISG) in the diagnosis and follow-up of patients with medullary thyroid carcinoma (MTC), we studied 25 patients with histologically proven disease; ISG was repeated after surgery in two patients. The antibody, either an anticarcinoembryonic antigen (CEA) or an antichromogranin A (CgA) biotinylated monoclonal antibody (MAb) or a cocktail of the two biotinylated MAbs was first injected. After 24 h, avidin was administrated i.v., followed by 111In-labelled biotin 24 h later. Fifty-two lesions were visualised. Six primary tumours, diagnosed by increased calcitonin levels, were all correctly diagnosed; 47 recurrences, also suspected by blood tumour markers, were detected and confirmed by cytology or histology. In one case, single photon emission tomography allowed the detection of small lymph nodes with a diameter of 4-7 mm. These lesions, not judged neoplastic by ultrasound, were confirmed to be neoplastic by fine needle aspiration. Pretargeted ISG correctly localises primary tumours and recurrences in MTC patients, when the only marker of relapse is serum elevation of calcitonin. With this three-step pretargeting method, cocktails of potentially useful MAbs can be used, avoiding false-negative studies that may occur when CEA or CgA are not expressed.

Immunoscintigraphy using technetium-99m-labeled anti-NCA-95 antigranulocyte antibodies as an adjunct to echocardiography in subacute infective endocarditis

Objectives. This study was performed to assess the clinical value of immunoscintigraphy in subacute infective endocarditis.Background. Radiolaheled granulocytes can reveal inflammatory lesions.Methods. Using technetium-99m-labeled anti-NCA-95 antigranulocyte antibodies, planar scintigraphy and single-photon emission computed tomography of the thorax were performed in 72 consecutive patients with suspected endocarditis. Each patient also underwent transthoracic and, if findings were negative, transesophageal echocardiocardiography.Results. Thirty-three patients were found to have endocarditis on the basis of clinical criteria (surgical confirmation in 17 patients), and the remaining 39 served as control subjects. Initial scintigraphy was true positive in 26 patients (sensitivity 79%) and false positive in 7 (specificity 82%). Echocardiography was true positive in 29 patients (sensitivity 88%) and false positive in 1 (specificity 97%). Scintigraphy was positive in the four patients with false negative echocardiography, and echocardiography was positive in the seven patients with false negative scintigraphy. Thus, the combination of scintigraphy and echocardiography yielded a sensitivity of 100% and a specificity of 82%. In 10 of the 11 patients with two to three follow-up studies, scintigraphy became negative prallel to clinical improvement, indicating decreasing floridity of the inflammatory process.Conclusions. Immunoscintigraphy in patients with subacute infective endocarditis provides valuable diagnostic information in equivocal echocardiographic findings and may be used to monitor antibiotic therapy.

Immunszintigraphischer Metastasennachweis bei malignen Melanomen im Kopf-Hals-Bereich

The value of immunoscintigraphy in patients with metastatic malignant melanoma of the head and neck is compared with clinical, radiological and histological findings. 25 immunoscintigraphic examinations in 16 patients were evaluated. Scintigraphy was performed during primary and follow-up diagnosis of head and neck melanoma of the skin (n = 8), nose and sinuses (n = 3), petrosal bone (n = 1) and sclera (n = 1) as well as in cervical lymph node metastases of distant melanoma (n = 2) and melanoma of an unknown primary tumour (n = 1). Immunoscintigraphy was performed with 99mTc-radiolabelled melanoma specific antibodies against a melanoma-associated cell membrane-bound antigen (glycopolypeptide). The sensitivity of the method was 88%, specificity was 80%. The prior significance of immunoscintigraphy is based on the detection of occult cervical lymph node metastases not detectable by means of palpation and radiography. Pulmonary and liver manifestations could not be safely identified due to the physiological enhanced blood pool in these organs. The results obtained indicate that immunoscintigraphy may yield more information about the status of pathologically altered tissue and in certain cases may influence the therapeutic procedure.

Immunoscintigraphy in patients with colorectal, ovarian, and prostate cancer. Results with site‐specific immunoconjugates

Application of monoclonal antibody (MoAb) technology to cancer management is discussed by reviewing the development and clinical evaluation of two MoAb-based immunoscintigraphic agents (111In-satumomab pendetide [OncoScint CR/OV-In] and 111In-CYT-356; Cytogen Corporation, Princeton, NJ). Both agents were prepared using a site-specific MoAb modification method that preserves the immunoreactivity of the radiolabeled immunoconjugate. 111In-satumomab pendetide is an 111In-labeled conjugate of the murine MoAb B72.3, which is directed to TAG-72, an antigen expressed by the majority of adenocarcinomas. By providing information that complements the results of standard radiographic diagnostic modalities, this imaging agent can aid in the treatment of patients with colorectal or ovarian cancer. Immunoscintigraphy with 111In-satumomab pendetide has been shown to assist in medical-surgical management by detecting occult extrahepatic lesions, clarifying equivocal results of other diagnostic imaging tests, and evaluating the extent and resectability of known tumor lesions. 111In-CYT-356 is an 111In-labeled conjugate of the murine MoAb 7E11-C5.3, which is reactive with prostatic carcinoma, benign prostatic hypertrophy, and, to a lesser extent, normal prostatic tissue. Results of preliminary clinical investigations suggest that 111In-CYT-356 immunoscintigraphy can be useful for the presurgical staging of prostatic carcinoma and for the detection of occult distant disease in patients with negative or equivocal results on standard imaging tests. Results with these site-specifically radiolabeled immunconjugates demonstrate the clinical utility of MoAb-based imaging agents in the treatment of patients with solid tumors.

Immunoscintigraphy in patients with colorectal, ovarian, and prostate cancer. Results with site-specific immunoconjugates

Immunoscintigraphy in patients with colorectal, ovarian, and prostate cancer. Results with site-specific immunoconjugates

New diagnostic imaging in rectal cancer: endosonography and immunoscintigraphy.

Endosonography of the rectum, combining the advantages of both endoscopy and sonography, provides information not at present available from other imaging modalities. It is remarkably accurate in the pre-operative assessment of tumor penetration. In the evaluation of lymph nodes, the specificity and sensitivity is 83% and 72%, respectively. For the detection of local recurrence in asymptomatic patients promising results can be obtained. In contrast, the potential benefits of immunoscintigraphy in patients with rectal cancer have yet to be determined but preliminary results indicate that immunoscintigraphy in combination with endosonography may assist the surgeon in confirming or excluding the suspicion of recurrence.

Anti-beta HCG abdominopelvic immunoscintigraphy in patients with resistant gestational trophoblastic disease.

The clinical utility of abdominopelvic immunoscintigraphy (IS) using anti-beta HCG-labelled monoclonal antibodies was evaluated in six patients with resistant gestational trophoblastic disease and no common pathological site. Five patients with abnormal retrovesical uptake had persistence of uterine trophoblastic disease confirmed on hysterectomy. Four of these patients are now in remission. It is concluded that IS provides a useful indication for surgery when a single abnormal uptake site is found.

Improvement by affinity chromatography on antiidiotypic monoclonal antibodies (MAbs) of immunoreactivity andin vivo targeting of radiolabelled anti-HMW-MAA MAb TP61.5 in nude mice bearing human melanoma lesions

The human high-molecular-weight melanoma-associated antigen (HMW-MAA) represents a useful marker for immunoscintigraphy in patients with melanoma. Since injection of a radiolabelled anti-HMW-MAA monoclonal antibody (MAb) visualizes only about 60% of melanoma lesions, approaches are being developed to increase the sensitivity of immunoscintigraphy. One of them aims at improving the immunoreactivity of radiolabelled anti-HMW-MAA MAbs, since this approach may improve the targeting of radiolabelled MAbs to melanoma lesions. We have previously shown that affinity chromatography on insolubilized anti-idiotypic MAbs is a useful method for purifying immunoreactive anti-HMW-MAA MAb TP61.5 from 125I-labelled MAb preparations and that not all the anti-idiotypic MAbs are useful for this purpose. Since the increasing number of available anti-idiotypic MAbs is likely to facilitate the application of this procedure in many antigenic systems, we have now tested criteria to select anti-idiotypic MAbs suitable for the purification procedure. Furthermore, we have investigated the effect of the increase in immunoreactivity of 125I-MAb TP61.5 on its in vivo targeting to human melanoma lesions transplanted into nude mice. Among the 3 anti-idiotypic MAbs tested, the most effective in purifying immunoreactive MAb TP61.5 molecules following radiolabelling is MAb TK7-110, with which 125I-MAb TP61.5 displays an immunoreactivity similar to that displayed with melanoma cells. This parameter may represent a useful criterion to identify anti-idiotypic MAbs suitable for the purification procedure, if the present results are confirmed with a large number of anti-idiotypic MAbs in different antigenic systems. We have also shown that an incubation time for up to 4 hr of 125I-MAb TP61.5 with insolubilized MAb TK7-110 is the most effective in increasing immunoreactivity and in recovering immunoreactive MAb applied to the affinity matrix. The increase in the immunoreactive fraction of 125I-MAb TP61.5 significantly increases its specific localization in human melanoma lesions transplanted into nude mice. These results suggest that purification of radiolabelled immunoreactive anti-HMW-MAA MAb TP61.5 by affinity chromatography using anti-idiotypic MAb TK7-110 represents a useful approach to increasing the sensitivity of immunoscintigraphy in patients with melanoma.

Purification of anti-epithelial mucin monoclonal antibodies by epitope affinity chromatography

Monoclonal antibodies against the protein core of epithelial mucins have been found to react with the immunodominant sequence P D T R P A P (Burchell et al., 1989; Price et al., 1990a). Two immunoadsorbent matrices were prepared by linking the peptide A P T R P P A P G to CNBr-activated Sephorose and by linking the peptide C A P D T R P A P G to activated thiol-Sepharose, so that each immunoadsorbent contained the immunodopinant motif. Anti-epithelial mucin antibodies (anti-breast carcinoma antibodies, anti-purified mucin antibodies and anti-human milk fat globule antibodies) were examined for reactivity with these preparations. The initial tests indicated that the substituted CNBr-activated Sepharose displayed lower non-specific antibody binding and this matrix was selected for further investigation. The anti-mucin antibodies were shown to react specifically with this affinity matrix and irrelevant antibodies failed to bind. A Sepharose-peptide immunoadsorbent column was examined for its capacity to purify several of these anti-mucin antibodies and it was determined that this procedure was highly efficient - purified IgG and IgM antibodies could be isolated from either hybridoma tissue culture supernatants or ascitic fluids. The capacity of the column was in excess of 40 mg antibody protein per ml of gel for the IgG3 antibody, C595 (anti-urinary mucin) and at least 10 mg antibody protein per ml of gel for the IgM antibody, NCRC-11 (anti-breast carcinoma). The procedure described permits the efficient purification of anti-mucin antibodies and provides a product which would be suitable for further investigations requiring highly immunoreactive antibodies (e.g., for radioimmunotherapy or immunoscintigraphy in patients with malignant disease).

Selective tumor localization of radiolabeled anti-human melanoma monoclonal antibody fragment demonstrated in the nude mouse model

Monoclonal antibodies (Mab) directed against distinct epitopes of the human 240 kD melanoma-associated antigen have been evaluated for their capacity to localize in human melanoma grafted into nude mice. A favorable tumor to normal tissue ratio of 13 was obtained with intact 131I-labeled MAb Me1-14. This ratio was further increased to 43 and 23 by the use of F(ab')2 and Fab fragments, respectively. The specificity of tumor localization was demonstrated by the simultaneous injection of F(ab')2 fragments from MAb Me1-14 and anti-CEA MAb 35, each labeled with a different iodine isotope, into nude mice grafted with a melanoma and colon carcinoma. The fragments from both MAb localized with perfect selectivity in their relevant tumor as shown by differential whole body scanning and by direct measurement of the two isotopes in tumors and normal tissues. These in vivo experimental results suggest that the F(ab')2 fragment from MAb Me1-14 is suitable for melanoma detection by immunoscintigraphy in patients.

Clinical implications for immunoscintigraphy in patients with ovarian malignancy: a preliminary study using monoclonal antibody 791T/36.

Twelve patients with suspected primary and recurrent carcinoma of the ovary have undergone immunoscintigraphy with an antitumour monoclonal antibody in order to assess the impact of the technique on patient management. Consistent tumour uptake of radiolabelled antibody was visualized in malignant tumours after subtraction of the blood background activity. Eight patients were imaged before surgery and in all of these the sites of uptake visualized on the images agreed with the surgical findings. In one patient with recurrent disease the imaging information was used as an aid for establishing the extent of external beam radiotherapy. A repeat study in this patient 6 months later revealed a reduction in the size of the tumour, which still concentrated labelled antibody and confirmed the viability of repeat investigations. Immunoscintigraphy was capable of providing diagnostic information which may offer an alternative to second-look surgery in these patients.