Radioimmunoscintigraphy Research Articles

Radioimmunoscintigraphy of colorectal carcinoma with a 111In-labelled anti-TAG-72 monoclonal antibody.

Radioimmunoscintigraphy (RIS) of colorectal carcinoma with a 111In-labelled anti-TAG-72 monoclonal antibody (CYT-103) has been performed in 24 patients with five primary lesions and 10 suspicious of recurrence (in one of these patients two RIS were made). Histopathological confirmation of the disease and surgical liver examination were carried out in all primary tumours and in 12 possible recurrences. In the remaining eight patients a final diagnosis was established according to the clinical course and other diagnostic procedures. Planar and tomographic scans were obtained at 48 and 72 h postinjection in all patients. All primary tumours were detected by RIS. In the group with recurrences confirmed pathologically the results were nine true positive, two true negative and one false positive in a patient affected only with liver disease. The nine true positive studies corresponded to four positive by computed tomography (CT), four negative by CT and one nonconclusive by CT. Surgical liver examination results were 15 true negative and two false negative. No correlation was found between serum levels of carcinoembryonic antigen or TAG-72 and the detection of the lesions. In 10 patients human anti-mouse antibody (HAMA) levels were studied. In conclusion, RIS with an anti-TAG-72 monoclonal antibody is a useful technique for the study and localization of colorectal tumours, mainly in cases of recurrence, being also indicated in patients with normal TAG-72 serum levels.

Radioimmunodetection of colorectal cancer metastases with 131I-labeled monoclonal antibody B72.3: a pilot study to determine efficacy of detection and pharmacokinetics.

We performed radioimmunoscintigraphy (RIS) and/or pharmacokinetic (PCK) studies in 12 patients with primary or metastatic colorectal carcinoma, utilizing an intravenous administration of 1-4 mCi (1 mg) of 131I-B72.3 monoclonal antibody. Metastatic lesions were correctly identified in 4/8 patients by RIS. Two patients with small lesions (> 2 cm diameter) had a false-negative RIS scan. Two patients had a true-negative RIS scan. Optimal images were obtained at 1 week postinjection. PCK studies showed that the plasma clearance of 131I-B72.3 was biexponential with an alpha-phase half-life ranging from 0.5 to 7.1 hr and a beta-phase half-life ranging from 47.5 to 85.3 hr. Systemic and renal clearance data indicated that 131I-B72.3 was cleared very slowly and almost entirely by deiodination. This pilot study was conducted to gain an understanding of the pharmacokinetics of this radiolabeled antibody. On the basis of these data, we are now studying second-generation antibodies as part of our long-range objectives to incorporate them in early detection and treatment protocols.

Tumour detection and localization using 99Tcm-labelled OV-TL 3 Fab?? in patients suspected of ovarian cancer

Fab' fragments of the monoclonal antibody OV-TL 3, that recognizes an ovarian carcinoma-associated antigen (OA3), were labelled with 99Tcm using D-glucarate as a ligand. Twenty patients suspected of having primary or recurrent ovarian cancer received intravenously 1 mg of the Fab' labelled with 740 MBq 99Tcm. Both planar and single photon emission computed tomographic (SPECT) scintigraphy were performed up to 30 h after intravenous infusion. In 19 out of 20 patients surgical and histopathological evaluation was performed between 2 and 6 days postinfusion. Imaging results were compared with X-ray computed tomography (CT), ultrasonography (US) and CA 125 serum level. Blood clearance was fast with median t1/2 beta of 9.5 h. Thirty-seven per cent of the injected dose (% ID) was excreted in the urine within the first 24 h, whereas 7% ID was excreted in the 24 h faeces. In one patient with an OA3 negative ovarian carcinoma, radioimmunoscintigraphy (RIS) did not visualize the tumour. In two other patients a benign ovarian cyst was found, also showing no elevated uptake. In 13 out of 17 patients ovarian cancer lesions were detected with RIS, whereas CT and US detected lesions in, respectively, 15 and 12 patients. Of 36 surgically defined tumour deposits larger than 1 cm in diameter, 53% were detected and localized with RIS, whereas CT and US detected 61 and 40%, respectively. Radioimmunoscintigraphy with 99Tcm-OV-TL 3 Fab' is less distressing for the patients but the overall imaging performance is not improved when compared with 111In-OV-TL 3 F(ab')2.

Radioimmunoscintigraphy of colorectal carcinoma with a 99Tcm-labelled anti-CEA monoclonal antibody (BW 431/26).

Radioimmunoscintigraphy (RIS) with BW 431/26 monoclonal antibody (MoAb) labelled with 99Tcm (962 MBq) has been performed in 64 patients with colorectal carcinoma, one of them with two independent tumours. The group consisted of 46 primary lesions, 15 pelvic recurrences and four suspected recurrences which were shown to be liver metastases. Imaging of liver was obtained in all patients, but surgical liver examination was performed in only 56 of them. Planar scans were obtained at 4 and 24 h postinjection. Tomographic images were also performed in five patients. The final diagnosis was confirmed in all patients by their clinical course and by findings at surgery and pathology. A comparative study between the RIS results and the final diagnosis gave a global sensitivity in primary tumours and pelvic recurrences of 59.7% with an accuracy of 59.0%. When rectal tumours were excluded, the results were 81.1 and 84.9%, respectively. In liver metastases the sensitivity was 50%, with an accuracy of 85.7% and a specificity of 100%. No correlation has been found between CEA serum levels and lesion detection. In conclusion, RIS is a useful technique for the study and localization of colorectal tumours, being also indicated in patients with normal carcinoembryonic antigen (CEA) serum levels and clinical suspicion of illness.

Radioimmunodetection of human colon cancer using 99mTc-MDP-MoAb-A7 in mice

Radioimmunoscintigraphy (RIS) using 99mTc-labeled A7, a monoclonal antibody (MoAb) against a human colorectal cancer, was performed in nude mice bearing a human colon cancer, HCT-15. MoAb-A7 was labeled with 99mTc in the presence of methylene diphosphate (MDP). At 24 h post-injection of 99mTc-MDP-A7, colon cancer was clearly visualized, and the tumor-to-tissue ratio of 99mTc-MDP-A7 was higher than the ratio of 111In-DTPA-A7 which was described previously. These results suggest the possibility of the clinical application of 99mTc-MDP-A7 for RIS of a human colon cancer.

Radioimmunoscintigraphy of Gynecologic Tumors with 131I-Labeled Anti-Plap Monoclonal Antibodies

Radioimmunoscintigraphy (RIS) was performed in 20 patients with gynecologic tumors, 14 ovarian, 5 cervical, and one endometrial carcinoma. One murine monoclonal antibody (mab) against placental alkaline phosphatase (H7) was used after radiolabeling with 131I. The labeling procedure yielded antibodies with specific activity varying between 60 and 73 MBq/mg mab. Each patient received 57 to 100 MBq of the preparation. RIS was performed 7 to 35 days later. Patients with ovarian adenocarcinoma had an accumulation of activity on RIS at tumor sites (79%, 11/14) verified by ultrasonography, CT, and clinical examination. A low or absent accumulation of activity was seen in patients with cervical tumors. The patient with an endometrial adenocarcinoma was seen to have an activity accumulation at RIS corresponding to tumor sites determined by ultrasound and/or CT. It is concluded that RIS using monoclonal antibodies against placental alkaline phosphatase can provide information which will supplement that gained from other investigations of patients with ovarian adenocarcinomas.

Diagnostic evaluation of radioimmunoscintigraphy (RIS) using 123I-labeled monoclonal antibodies against human granulocytes (Mab-47) for the detection of prosthetic vascular graft infection

Diagnostic evaluation of radioimmunoscintigraphy (RIS) using 123I-labeled monoclonal antibodies against human granulocytes (Mab-47) for the detection of prosthetic vascular graft infection

Comparative study of RIS with the 131I-OC 125 F(ab′) 2 Mab and CT scan prior to second look operation for ovarian cancer

A tumour-associated radiolabelled monoclonal antibody (Mab) 131I-OC 125 F(ab′) 2 was used to investigate 27 patients 2 weeks after their last chemotherapy regimen and prior to second-look surgery for ovarian cancer. We did compare the radioimmunoscintigraphy (RIS) findings with the CT scan results and the second-look operation data. In 23 out of 27 cases the RIS results correlated with the operation findings, while there were four false-negative results. Computed tomography (CT) scans correlated in 17 out of 23 cases with the operative findings, while there were six false-negative results. We concluded that RIS is more specific in detecting the tumour site within the pelvis, while CT scan is superior in detecting liver metastases.

Clinical Value of Radioimmunoscintigraphy in the follow-up of Ovarian Carcinoma: A Prospective Study

Twenty-five patients treated with debulking surgery and chemotherapy for ovarian cancer were prospectively studied to evaluate the efficacy of radioimmunoscintigraphy (RIS) in detecting residual tumor before second-look surgery. RIS was performed with the monoclonal antibody OC125 F(ab')2 labelled with I-131 without knowledge of clinical data and compared with subsequent surgical results. Second look showed tumor persistence in 12 patients, mostly characterized by small lesions. The overall diagnostic sensitivity of RIS was 50% and the specificity was 85%. In particular, RIS showed better sensitivity for pelvic tumor localizations than for abdominal sites (73% vs 33%); this was due to the inability of RIS to detect upper abdominal lesions. Therefore, our conclusion is that, at present, RIS cannot substitute surgical second-look in the management of ovarian cancer, however, considering that also ultrasonography, computer tomography and magnetic resonance are not always able to give definite diagnostic evidence in the follow-up of ovarian carcinoma, RIS could be added to these procedures to balance the limitations of each method. In this regard, the best application of RIS could be in the follow-up of patients with marker elevation without clinical evidence of disease, especially in the case of pelvic fibrosis or adhesions due to previous therapy, where the other non-invasive tools can give doubtful diagnostic results.

Wertigkeit der Radioimmunszintigraphie im Vergleich zur Computertomographie in der Diagnostik und Verlaufskontrolle des primären Ovarialkarzinoms

In this prospective study the diagnostic merit of radioimmunoscintigraphy (RIS) was compared with computed tomography (CT) and operation in the primary diagnostic procedure and follow-up of women with suspected ovarian cancer. In primary diagnosis, sensitivity, specificity, and diagnostic accuracy was 100%, 60% and 90% for RIS. In follow-up, sensitivity for local recurrence was slightly higher in CT than in RIS. It was possible to detect peritoneal carcinosis in the pelvis and lower abdominal region better with RIS, but in the upper abdominal region, peritoneal carcinosis was detected better with CT. If no differentiation between benign or malignant lesion, is possible with CT, differentiation will in many cases be possible with RIS.

The biological approach to radioimmunoscitigraphy

The authors have analysed the theoretical and clinical implications of a biological approach to radioimmu-noscintigraphy (RIS), a new diagnostic technique based on the in vivo reaction between radiolabelled monoclonal antibodies and tumor-associated antigens expressed by the neoplastic cells. The assumption is that, as in all radioisotopic procedures, the radioimmunoscintigraphic image is the expression of differences in concentration (and not in density) between adjacent tissues. This “biological premise” is analysed to demonstrate a possible role of RIS not only in diagnosis but also in prognosis and therapy. A comparison with other imaging procedures and with histopathology, considered as the “gold stand-ard” of the present-day morphological approach to diagnosis, is also discussed. Finally, biological premises, as well as the initial results and prospects regarding the use of high doses of radiolabelled monoclonal antibodies for therapeutic purposes are presented.

4 Radio-immunoscintigraphy and intraoperative tumour detection by means of anti-tumour antibodies in patients with ovarian cancer

A hand-held gamma-ray detection probe was developed by us to circumvent the problems of conventional radio-immunoscintigraphy (RIS). The intraoperative use of this probe in terms of radionuclide-assisted surgery (RAS) should help to overcome problems associated with insufficient accumulation by the tumour of the radio-active antibodies, unfavourable localization of tumour sites, collimation problems, etc., in patients with ovarian cancer. The probe was designed as a scintillation counter. Twelve patients were operated upon and investigated by RAS. It could be shown that RAS is able to detect tumour tissue intraoperatively, although we have already seen that improvements in the probe are necessary to make the method of real clinical value.

Radioimmunoscintigraphy of ovarian cancer with 131-iodine labeled OC-125 antibody fragments.

Radioimmunoscintigraphy (RIS) with 131I labeled OC-125 F(ab')2 monoclonal antibody fragments was prospectively studied in 43 women for primary diagnosis and follow up of ovarian cancer. Total body planar photoscans with a scintillation camera were performed one to seven days after antibody application and results were compared with operation and or CT examination. By the region of interest technique the tumor to non tumor tissue ratio (T/N) was calculated in vivo. Sensitivity in primary diagnosis was 100% (10/10), specificity 33% (1/3). For local recurrency, sensitivity was 86% (19/22), for metastatic loci 80% (17/21). Specificity was 75% and 50%. T/N ratio was in the rage from 1.3 to 2.8. Sensitivity for ovarian cancer is high in primary diagnosis and follow up. By the region of interest technique it is possible to detect small recurrencies and to presume peritoneal carcinosis. Antibody accumulations in diseases different from ovarian cancer however diminish specificity.

Diagnosis of ovarian cancer with radiolabelled monoclonal antibodies: Our experience using 131I—B72.3

Radioimmunoscintigraphy (RIS) using 131I-labelled B72.3, a monoclonal antibody (MoAb) reacting against a tumor associated antigen (TAA) called TAG-72, has been performed in 36 patients with epithelial ovarian cancer. The patients were divided in three groups as follows: 17 patients with primary cancer before any therapy (Group 1); 10 patients studied after a partial therapeutic approach, having either bulky or minimal disease (Group 2); 9 patients with microscopic disease or in clinical remission at the moment of the study (Group 3). All the most important epithelial histotypes, including mucinous, were present. Results were confirmed at surgery and/or by other diagnostic procedures. Immunocytochemical (ICC) and immunocytofluorimetric (ICF) studies on ascitic collections were performed in order to demonstrate specificity of B72.3 and TAG-72 distribution on neoplastic cells. Immunohistochemistry (IHC) on tissue sections was also obtaïned. No cross reactions between B72.3 and mesothelial cells in the presence of specific uptake by neoplastic cells was found. Moreover, a non-homogeneous distribution of TAG-72 in the neoplastic population was demonstrated by ICF. RIS proved the intraperitoneal presence of disease in 15 out of 17 and in 5 out of 10 patients in Groups 1 and 2, respectively. One out of four (Group 1) and two out of four (Group 2) extraperitoneal metastases were also seen. False negative results were explained by lack of expression of the antigen, size and location of the lesion, and patho-physiological conditions. One false positive due to an aspecific uptake by a post-surgical active scar was also observed in a disease-free patient.

5 Clinical experience with single photon emission computed tomography (spect) — radioimmunoscintigraphy (RIS)

5 Clinical experience with single photon emission computed tomography (spect) — radioimmunoscintigraphy (RIS)

Radioimmunoscintigraphy Using Monoclonal Antibodies before Second-Look Surgery in Patients Suffering from Ovarian Cancer

19 patients with a known history of ovarian cancer were investigated by radioimmunoscintigraphy (RIS) to look for recurrent disease a few days before second-look surgery. The tumor-associated monoclonal antibody HMFG-2 (400 micrograms/patient) was injected intravenously after labeling with radioactive 123I (0.5-2.2 mCi/patient). Scans were reviewed for activity accumulations due to uptake of the tumor-associated antibody by tumor sites. In 15 out of the 19 cases the scan results correlated with the intraoperative findings. There were 2 false-positive and 2 false-negative scans, the latter in patients with subclinical disease. The smallest lesion detected by radioimmunoscintigraphy had a diameter of 1.5 cm. In 3 patients, tumor sites were identified that had been missed by all other routinely performed methods of investigation including transmission computed tomography. These data indicate that RIS is of considerable clinical value in the early detection and localization of recurrent ovarian cancer and may, therefore, improve the management of these patients.

Radioimmunszintigraphie mit SPECT: Methodik, Probleme und klinische Erfahrungen

Radioimmunoscintigraphy (RIS) with 111ln- and 131 I-labelled monoclonal anti bodies (MAbs) against CEA and/or CA 19-9 was performed in 83 patients with various gastrointestinal carcinomas. A total of 276 body regions could be examined. The results of planar scintigraphy and SPECT were compared intraindividually. Using 111 In-labelled MAbs the sensitivity of RIS was significantly improved by SPECT (88.9 vs. 52.4% with planar scintigraphy, p <0.01). For131 l-labelled MAbs the effect was smaller (83.9 vs. 65.6% with planar scintigraphy, n.s.). This finding can be explained by different kinetics and biodistribution of the used MAb preparations.111 In-labelled MAbs with long whole-body retention and rapid blood clearance reveal ideal qualities for SPECT; on the other hand, the short whole-body retention of131 l-labelled MAbs leads to small count rates and therefore long counting times that make delayed SPECT unsuitable in clinical practice