Katrine Riklund Åhlström

Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation

Abstract. Familial amyloid polyneuropathy (FAP) associated with transthyretin (TTR) mutations is the commonest type of hereditary amyloidosis. Plasma TTR is produced almost exclusively in the liver and orthotopic liver transplantation is the only available treatment, although the clinical outcome varies. Serum amyloid P component (SAP) scintigraphy is a method for identifying and quantitatively monitoring amyloid deposits in vivo, but it has not previously been used to study the outcome of visceral amyloid deposits in FAP following liver transplantation. Whole body scintigraphy following injection of iodine-123 labelled SAP was performed in 17 patients with FAP associated with TTR Met30 and in five asymptomatic gene carriers. Follow-up studies were performed in ten patients, eight of whom had undergone orthotopic liver transplantation 1–5 years beforehand. There was abnormal uptake of 123I-SAP in all FAP patients, including the kidneys in each case, the spleen in five cases and the adrenal glands in three cases. Renal amyloid deposits were also present in three of the asymptomatic carriers. Follow-up studies 1–5 years after liver transplantation showed that there had been substantial regression of the visceral amyloid deposits in two patients and modest improvement in three cases. The amyloid deposits were unchanged in two patients. In conclusion, 123I-SAP scintigraphy identified unsuspected visceral amyloid in each patient with FAP due to TTR Met30. The universal presence of renal amyloid probably underlies the high frequency of renal failure that occurs in FAP following liver transplantation. The variable capacity of patients to mobilise amyloid deposits following liver transplantation may contribute to their long-term clinical outcome.

Gastric emptying before and after liver transplantation for familial amyloidotic polyneuropathy, Portuguese type (Val30Met).

Liver transplantation is an accepted treatment of familial amyloidotic polyneuropathy (FAP), Portuguese type (Val30Met), and the outcome so far seems promising. Gastric retention with natisea and vomiting are common complications of the disease, and may interfere with immuno-suppression therapy and prolong recovery after liver transplantation. The aim of this study was to assess the frequency of gastric retention in FAP patients and to evaluate the impact liver transplantation has on gastric emptying. Twenty-two patients, who had undergone liver transplantation, and had been re-examined for gastric retention after the procedure, were included in the study. Gastric emptying was recorded by scintigraphy after the ingestion of a 99m-technetium (99mTc)- labelled meal (omelette). The half time (T50) of the emptying phase was calculated. Gastrointestinal symptoms before and after transplantation were recorded, and the majority of patients were also subjected to an upper endoscopic examination, where the presence of solid residual in the stomach was regarded as consistent with gastric retention. A high frequency of gastric retention was noted among the patients both before and after transplantation, and no significant improvement for the group was noted, even though decreased gastric emptying was noted for patients with a duration of the disease for less that 4 years. Patients who improved their nutritional status after transplantation had a faster gastric emptying than those who deteriorated. From our findings it can be concluded that gastric retention is a common complication of FAP and that gastric emptying in patients with longstanding disease (≥ 4 years) is unchanged after liver transplantation.

Visual consciousness: Dissociating the neural correlates of perceptual transitions from sustained perception with fMRI

To investigate the possible dichotomy between the neurophysiological bases of perceptual transitions versus sustaining a particular percept over time, an fMRI study was conducted with subjects viewing fragmented pictures. Unlike most other perceptually unstable stimuli, fragmented pictures give rise to only one perceptual transition and a continuous period of sustained perception. Earlier research is inconclusive on the subject of which anatomical regions should be attributed to what temporal aspect of perception, and the aim of the present study was to shed more light on the subject. In this study occipitotemporal and fronto-parietal regions were found to be activated for both aspects. However, regions in the medial-temporal lobe were activated specifically for transitions, whereas medial and dorsolateral prefrontal regions were activated specifically for sustained perception. These results provide further support for the theory that the initial creation of perceptual awareness and upholding perceptual awareness over time are separate processes involving different brain regions.

Twenty Years with Monoclonal Antibodies: State of the art-Where do we go?

In this review, we have selected some parameters with the potential to improve the efficacy of RIL and RIT. Focus has partially been on the behaviour of radiolabelled antibodies in vivo in relation to properties and amounts of both target antigen and the antibodies used. If, out of the 28 factors listed in Table 1, some should be given preference in future work, it is our opinion that after the initial saturation of the tumour site a rapid decrease in redundant antibody is of significant importance. Furthermore, quantitative aspects of both antigens and antibodies should be more carefully evaluated when possible. By combining several of the listed approaches toward increasing efficiency, a more extensive use of RIL and RIT could be expected in the future.

Dosimetry of fractionated experimental radioimmunotargeting with idiotypic and anti-idiotypic anticytokeratin antibodies†

Repeated injections of iodine‐125 (125I)‐labeled tumor targeting anticytokeratin monoclonal antibody (TS1) and a nonlabeled antiidiotypic monoclonal antibody against TS1 (αTS1) were compared with a single injection of the radiolabeled TS1 in experimental radioimmunotargeting. Anti‐TS1 was used to remove nontargeting TS1.

Dosimetry of fractionated administration of 125I-labeled antibody at experimental radioimmunotargeting.

Radiotherapy of solid tumors is preferably performed in fractionated doses. Conversely, radioimmunotherapy with nuclide‐carrying antibodies delivers a continuously decreasing low dose rate during a longer time period after a single injection. In the current study, the same total amount of 125I‐labeled anticytokeratin monoclonal antibody (MoAb) was administrated in one, three, or ten injections and the dosimetry was evaluated.

MRI of the skeleton in prostate cancer staging.

Objective: To explore the value of MRI in the detection of bone metastases in newly diagnosed prostate cancer. Material and methods: MRI examinations of the axial skeleton in 76 patients with newly diagnosed prostate cancer were reviewed, and the relation of these findings to the serum level of prostate specific antigen (PSA) was examined. Results: MRI indicated bone metastases in 26/76 patients (34%) in the entire study group, in 4/24 (17%) with serum PSA <20 r ng/ml and in 22/52 (42%) with serum PSA >20 r ng/ml. Conclusions: These results suggest that MRI is a more sensitive indicator of suspected bone metastases than bone scintigraphy in the low range of serum PSA, but less sensitive in the high range. Further studies of MRI and bone scintigraphy in parallel in patients with serum PSA <20 r ng/ml are needed to elucidate their relative value in the staging of patients with prostate cancer.

Stability and Immunoreactivity of the Monoclonal Anticytokeratin Antibody TS1 after Different Degrees of Iodination

The immunoreactivity, stability and in vivo kinetics of an anticytokeratin 8 monoclonal antibody, TS1, were investigated following different degrees of labeling with 125I (0.2, 1 and 2-3 125I/TS1 MAb). By testing with ELISA, it was demonstrated that a high degree of iodination, i.e. > 2 125I/TS1, caused a rapid decrease in immunoreactivity to almost zero within 10 days. Furthermore, a complete degradation to low molecular weight fragments and free iodine was seen, as shown by SDS PAGE and autoradiography. The differently labeled radionuclide conjugates were injected into nude mice inoculated with HeLa Hep2 cells and tumor doses (estimated by MIRD formalism), tumor:non-tumor dose ratios, % I.D./gram tissue, Gy/MBq and in vivo kinetics of the differently labeled MAbs were determined. Despite the in vitro instability of the highest iodinated radionuclide conjugate, it was possible to deliver high doses to the tumors if the conjugate was injected into the animal immediately after completion of the iodination procedure. Increases from 1.4 Gy to 15.2 Gy delivered tumor dose were obtained with a tenfold increase in the specific activity, without alterations in the tumor:non-tumor tissue dose ratios. There is room for significant improvements in efficacy at radioimmunotherapy, which can be gained by optimizing the degree of iodination. For therapeutical applications a high degree of iodination may be an advantage.

Radioimmunodetection of ovarian cancer.

Radioimmunoscintigraphy (RIS) is a potentially valuable method for the detection of primary, secondary and recurrent malignant tumours. Antigens that have been used for monitoring as well as for RIS of ovarian carcinomas include CA 125, PLAP, HMFG, and CA 19-9. Between 70 and 100% of the tumours have been detected at RIS when these antigens have been used. Conventional methods, e.g., computerized tomography (CT) and ultrasonography (US), demonstrate similar or lower detection rate than RIS for tumour diagnosis. RIS gives additional information to conventional radiological methods (CT and US) for the detection of occult ovarian carcinomas. A review of earlier investigations is given and our own recent results using PLAP as a target antigen are presented. The future potential of the technology is discussed.

Radioimmunoscintigraphy with a novel monoclonal antiprostate antibody (E4)

Prostate cancer is one of the leading causes of death among men, despite achievements in diagnosis and therapy. Radioimmunolocalization and radioimmunotherapy of malignant tumors have demonstrated increasing potential and may become useful tools in the management of prostate cancer.