Radioimmunoscintigraphy for postprostatectomy radiotherapy: analysis of toxicity and biochemical control.

UNLABELLED: Our goal was to evaluate the role of radioimmunoscintigraphy (RIS) directed against prostate-specific membrane antigen (PSMA) in influencing postprostatectomy radiotherapy (RT) toxicity and biochemical control. METHODS: The records of 107 postprostatectomy RT patients were reviewed. The group for whom no RIS scan was obtained (group A, n = 54) was identified as was the group for whom a RIS scan was obtained (group B, n = 53). Group B was further subdivided into those who had a RIS and CT-scan correlation to aid in treatment planning (subgroup B1, n = 40) versus those who did not (subgroup B2, n = 13). Gastrointestinal (GI) and genitourinary (GU) toxicities were reviewed for each of these groups and subgroups and compared. Biochemical failures (defined as 2 successive PSA rises after a nadir of >or=0.2 ng/mL) were identified to generate biochemical failure-free survival (BFFS) curves for each of the groups and subgroups. RESULTS: No significant differences in late toxicity were observed between any group or subgroup. However, acute GI toxicity was higher in group B versus group A (P = 0.026), and acute GU toxicity was higher in subgroup B2 versus subgroup B1 (P = 0.050). Overall, most toxicity was grade 1 or 2; only one case of grade 3 toxicity and no cases of grade 4 or 5 toxicity were observed. Three-year BFFS was higher for group B versus group A (80.7% vs. 75.5%) and for subgroup B1 versus subgroup B2 (84.5% vs. 71.6%). On multivariate analysis of pretreatment (age, race), surgical/staging (stage, grade, margin status, extracapsular extension, lymph node status, seminal vesicle invasion, post-radical retropubic prostatectomy [RRP] prostate-specific antigen [PSA] nadir, maximum post-RRP PSA, and RRP-to-RT interval), and treatment (hormone therapy, RT dose, RT technique, RIS scan, and RIS/CT correlation) factors on BFFS, the only covariate reaching significance was RIS/CT correlation (P = 0.042). CONCLUSION: A small BFFS advantage was observed in patients for whom RIS was used to guide RT decision making and treatment planning; however, this advantage only reached significance in this study for those for whom the RIS/CT correlation was used to guide target definition. The improved PSA control using RIS was achieved with a small increase in acute toxicity but with no observed change in late toxicity. These findings can serve as the basis for prospective studies in this area of investigation.

Bone marrow scintigraphy with 99m Tc labelled monoclonal anti-NCA 90 Fab' fragment: a feasibility study and comparison of bone marrow uptake with 99m Tc labelled monoclonal anti-NCA 95 antigranulocyte antibody.

The aim of this retrospective study was to evaluate the usefulness of 99mTc labelled monoclonal anti-NCA 90 antigranulocyte antibody Fab' fragment (MN3 Fab') as a bone marrow imaging agent. One hundred and ten planar scans (88 patients) of the lumbar and sacroiliac regions as well as whole-body scans were performed after 1, 5 and 24 h. All the scans were evaluated visually and bone marrow uptake was determined semiquantitatively as count density ratio from sacroiliac-minus-background to background area. Results were compared to 50 age-matched patients with normal bone marrow scans obtained with the intact 99mTc labelled monoclonal anti-NCA 95 antigranulocyte antibody (BW 250/183) in a previous study. Seventy-three patients showed a physiological activity distribution in the central bone marrow. Ten patients showed a bone marrow extension, while in two patients central bone marrow depression was observed. Evaluation of the ribs, lower thoracic and upper lumbar spine was hampered by soft-tissue activity. Bone marrow uptake was 1.36+/-0.56 after 1 h, decreased thereafter and was significantly lower than that of BW 250/183 (P < 0.001). In conclusion, MN3 Fab' cannot be recommended for bone marrow scintigraphy, because relevant parts of the haemopoietically active bone marrow are not accessible to visual evaluation. A significant role of the semiquantitative evaluation of MN3 Fab' bone marrow uptake in patients with potential marrow depression seems unlikely.

Chronic post-traumatic osteomyelitis of the lower extremity: comparison of magnetic resonance imaging and combined bone scintigraphy/immunoscintigraphy with radiolabelled monoclonal antigranulocyte antibodies.

OBJECTIVE: A retrospective study of the validity of combined bone scintigraphy (BS) and immunoscintigraphy (IS) using (99m)Tc-labelled murine antigranulocyte antibodies (MAB) and magnetic resonance imaging (MRI) in chronic posttraumatic osteomyelitis. DESIGN AND PATIENTS: The results of MRI and combined BS/IS of 19 lesions in 18 patients (13 men, 5 women; mean age 45 years, range 27-65 years) were independently evaluated by two radiologists and one nuclear medicine physician with regard to bone infection activity and extent. The patient group was a highly selective collection of clinical cases: the average number of operations conducted because of relapsing infection was eight (range 2-27), the average time interval between the last surgical intervention and the present study was 6.5 years (range 3 months to 39 years), and from the first operation was 14 years (range 1.5-42 years). Interobserver agreement on MRI was measured by kappa statistics. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for MRI and the nuclear medicine studies. RESULTS: For MRI/nuclear medicine, a sensitivity of 100%/77%, a specificity of 60%/50%, an accuracy of 79%/61%, a PPV of 69%/58% and a NPV of 100%/71% were calculated. Four MR examinations were false positives because of postsurgical granulation tissue. A high degree of interobserver agreement was found on MRI (kappa=0.88). A low-grade infection was missed on two scintigrams, while four were false positive because of ectopic haematopoietic bone marrow, and in one examination the anatomical distortion resulted in an inaccurate assignment of the uptake leading to false positive findings. Image analysis was frequently hindered by susceptibility artefacts due to residual abrasions of metallic implants after removal of orthopaedic devices (15/18 patients); this led to limited assessment in 17% (3/18 patients). CONCLUSION: Acute activity in a chronic osteomyelitis can be excluded with high probability if the MRI findings are negative. In the first postoperative year fibrovascular scar cannot be distinguished accurately from reactivated infection on MRI and scintigraphy may improve the accuracy of diagnosis. MRI is more sensitive in low-grade infection during the later course than combined BS/IS. Scintigraphic errors due to ectopic, peripheral, haematopoietic bone marrow can be corrected by MRI.

Efficacy of monoclonal antibody 131I-B72.3 immunoscintigraphy of pancreatic adenocarcinoma xenografts in nude mice.

OBJECTIVE: To assess the efficacy of monoclonal antibody (MoAb) B72.3 for in vivo-immunoscintigraphy of pancreatic carcinoma in nude mice. DESIGN: Experimental controlled animal study. SETTING: University hospital, The Netherlands. SUBJECTS: 11 nude mice with subcutaneously xenografted human pancreatic carcinoma. INTERVENTIONS: Specific MoAb B72.3 and non-specific MoAb MOPC21 were iodinated with 131I and injected intraperitoneally in nude mice. Scintigrams were taken on days 1-10 and tumour:non-tumour ratios of the regions of interest (tumour, thorax, abdomen, background) were calculated. The mice were then killed for in vitro tissue counts. MAIN OUTCOME MEASURES: Tumour:non-tumour ratios in vivo and in vitro. RESULTS: Results of immunoscintigraphy on days 1, 2, and 6 were compared. In the B72.3-group all ratios were only moderately raised, the tumour:background ratio being the highest (2.35 (SD 0.67)) on day 6. There were no obvious differences between the ratios of the B72.3-group and the MOPC21-group. The results of tissue counts done at the end of the study, showed that tumour:non-tumour ratios were twice as high in the B72.3-group, suggesting some specificity of this MoAb. CONCLUSION: The results of our study suggest that MoAb B72.3 is not powerful enough for in vivo detection of pancreatic cancer as assessed in this xenograft model in nude mice.

Effect of circulating antigen on immunoscintigraphy of ovarian cancer patients using anti-CA125 monoclonal antibody.

The murine monoclonal antibody (mAb) 145-9 recognizes an epitope present on CA125 but different from the epitope defined by the mAb OC125. To evaluate the clinical usefulness of the 145-9 antibody, immunoscintigraphy was performed in ovarian cancer patients and the effect of circulating CA125 on tumor imaging was investigated. Two milligrams (74 MBq) of 111In-labeled 145-9 was injected intravenously into 11 patients with ovarian cancer. Pre-injection serum CA125 concentrations were between 166 U/ml and 7414 U/ml. Tumors were visualized in 10 of 11 patients. In two patients, lymph nodes that were not detected by other imaging modalities but were clinically suspected as metastases were visualized. There was no correlation between serum CA125 level and antibody uptake in the tumors. Immune complexes between the antibody and circulating antigen were observed in sera of all the patients, but the fraction of radioactivity in complex form did not correlate well with serum CA125 levels. The immune complexes survived in the circulation and the circulating radiolabel, including immune complexes, was still bound to solid-phase CA125. The plasma clearance rate and hepatic uptake of the antibody were not significantly affected by circulating CA125. In conclusion, the antibody 145-9 formed complexes with CA125 in vivo but this did not Compromise the outcome of antibody imaging. The antibody 145-9 can be used in immunoscintigraphy of ovarian cancer irrespective of serum CA125 level.

Tratamiento quirúrgico de la recurrencia del cáncer colorrectal / Surgical treatment in colorectal carcinoma relapses

Las mejoras en el campo del diagnóstico han llevado al cirujano general a hallar más recurrencias tempranas y localizadas, las que pueden ser extirpadas mediante cirugía. Este tratamiento agresivo se justifica debido a la poca efectividad coadyuvante observada con la quimio y radioterapia. Objetivo: análisis clínico retrospectivo de pacientes operados por recurrencia colorrectal. Material y métodos: selección de 20 casos sobre un total de 214, a quienes se les efectuó cirugía resectiva (14) o paliativa (6) por recurrencia. Resultados: la recurrencia más frecuente operada fue la pelviana (43,5 por ciento) abdominal (17,4 por ciento), hepática (13 por ciento) y perineal (8,7 por ciento). El tumor primario se localizó en recto (40 por ciento), colon derecho (30 por ciento), colon sigmoides (20 por ciento) y colon izquierdo alto (10 por ciento). El grado C de Dukes provocó las recurrencias más frecuentemente; seguido del B con invasión por contig³idad o de tipo mucoide. La morbilidad fue del 10 por ciento y la mortalidad para la cirugía resectiva del 7,1 por ciento y la paliativa, 16,6 por ciento (p=0,521). Conclusiones: este estudio sugiere que el tratamiento resectivo de la recurrencia por cáncer colorrectal prolonga la sobrevida; aunque ningún caso pasó los 48 meses. No se hallaron diferencias estadísticamente significativas respecto de la mortalidad con cirugía resectiva o paliativa. (AU)

Radioimmunolocalization and quantification of liver metastases and subcutaneous tumours from a human colonic cancer xenografted in the nude rat.

The purpose of the present investigation was to improve the conditions for radioimmunolocalization (RIL) and radioimmunotherapy (RIT) of colonic cancer, using experimental models of the human disease. A tumour model was created in the nude rat by intraportal injection of a mechanically disintegrated cell preparation of the human colonic cancer cell-line LS 174 T, producing liver metastases in a dose-dependent fashion. A conventional subcutaneous (s.c.) tumour model was also employed, where LS 174 T cells were inoculated into a hindleg of nude rats. A technique was developed for quantification of liver metastases by means of contrast-enhanced CT, using an iodinated lipid emulsion. CT-quantification proved feasible post mortem and also in vivo, the latter enabling repeated therapy evaluation in the same animal. Post mortem quantification of hepatic metastases was also accomplished by computer-based area calculation (CBAC) on serial liver sections. The three evaluation procedures were in agreement for quantification of intermediate and extensive hepatic metastatic growth, but not for livers with small and few metastases. A similar CT evaluation technique, may also be possible for human application. Several pharmacokinetic aspects of RIL were evaluated, using the 125I-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) preparations I-38S1, AEC 38 and II-16. MAb AEC 38 was produced by additional purification of I-38S1 by anion exchange chromatography. Most MAb I-38S1, AEC 38 and II-16 accumulated in the s.c. xenografts during the first 24 h, the maximum being reached on days 2-4, depending on the MAb preparation used. The patterns of uptake and clearance of AEC 38, I-38S1 and II-16, found in gamma camera registrations, were in agreement with those of external detector measurements. Additional purification of I-38S1 by anion exchange chromatography improved the in vivo MAb uptake in s.c. xenografts, but its immunoreactivity in vitro was impaired by this procedure. The uptake of I-38S1 in hepatic metastases was not size dependent and was higher than in s.c. xenografts, irrespective of the mode of MAb injection (i.p. or i.v.). Uptake of I-38S1 in s.c. xenografts was independent on injection mode. By contrast, in liver metastases there was a marked tendency toward a higher uptake of I-38S1 following i.p. vis-a-vis i.v. antibody administration, although not statistically significant, possibly due to an apparent variability between animals and between different liver metastases in the same rat. This variability was not evident for s.c. xenografts.(ABSTRACT TRUNCATED AT 400 WORDS)

[The demonstration and staging of bladder carcinoma. A comparative study between magnetic resonance tomography, computed tomography and radioimmunoscintigraphy]. / Nachweis und Stadieneinteilung des Harnblasenkarzinoms. Eine vergleichende Untersuchung zwischen Magnetresonanztomographie, Computertomographie und Radioimmunszintigraphie.

The purpose of the present study was to compare the effectiveness of MRI, CT and radioimmunoscintigraphy in the staging and detection of bladder cancers in 28 patients. We distinguish two groups: Group I included the tumour stages CIS-T3A and the second group the deep infiltrative tumours T3B-T4. MRI was slightly superior to CT in respect of tumour staging (75% correct results as compared to 63%). No understaging occurred with MRI, whereas in 22% of the cases the stage of the tumour was underestimated using CT diagnostics. Overstaging occurred in 25% of the MRI and 15% of the CT-diagnostics, respectively. RIS cannot distinguish the tumour groups, and hence this method is useful only for the detection of the primary tumour and metastases. In 77% of cases the tumour was detected and in 15% the tumour could be safely excluded.

Radiolabeled monoclonal antibodies (for the radiology administrator).

Cheaper, faster, safer, these are not the attributes of 1993 automobiles, but criteria for new diagnostic tests in medicine. To achieve these characteristics, medicine is increasingly looking to biotechnology for answers. And the mother of all biotechnology is monoclonal antibody research. In past issues, Administrative Radiology published articles discussing the role of biotechnology in the development of radiopharmaceuticals used in nuclear medicine. In this issue, Richard Wahl, M.D., reviews, in plain talk, the current status and prospects for diagnostic imaging with radiolabeled monoclonal antibodies. Are there any such procedures of value today? Are there any that are FDA approved? Will there ever be such agents that are either useful or approved? If so, will any insurance carrier pay for them? For the answers to these and other "hot" questions, the reader is encouraged to continue on and read this month's Technology Review section.

Visualization of myocardial infarction 6 h after injection of 111In-antimyosin antibodies using a blood pool subtraction technique.

111In-antimyosin antibodies are capable of visualizing myocardial infarction (MI). Because of slow blood clearance, images are usually recorded 24 or 48 h postinjection. In this pilot study, a blood pool subtraction technique, which makes it possible to visualize MI 6 h postinjection, is validated. Twenty-five patients with proven MI (16 anterior, 9 inferior) were imaged a few minutes, 6 and 24 h after an injection of 111 MBq 111In-labelled antimyosin antibodies. Three planar views are obtained each time. Using software which performs the geometric registration, the grey level normalization and the subtraction of images, the blood pool image (obtained a few minutes postinjection) is subtracted from the 6 h image. The resulting image is the blood pool corrected 6 h image. The 24 h images and the blood pool corrected 6 h images were interpreted blindly and the number of correct, incorrect and impossible MI localizations was counted. The number of correct localizations is 19/25 for the standard 24 h images and 22/25 for the blood pool corrected 6 h images. Then, with this blood pool subtraction method, it is possible to visualize MI 6 h postinjection. This has to be taken into account when discussing the role of antimyosin scintigraphy in the management of patients with MI.