Positive I-123-MIBG-scintigraphy in osteosarcoma.

I-123-MIBG scintigraphy has become a standard imaging technique in the detection of neuroendocrine or neurocrest derived tumors, especially neuroblastoma and pheochromocytoma. We report on a positive I-123-MIBG uptake in a pediatric osteosarcoma patient and demonstrate, that unusual results still occur with this established imaging method.

Tc-99m DTPA perfusion scintigraphy and color coded duplex sonography in the evaluation of minimal renal allograft perfusion.

AIM: The clinical impact of perfusion scintigraphy versus color coded Duplex sonography was evaluated, with respect to their potential in assessing minimal allograft perfusion in vitally threatened kidney transplants, i.e. oligoanuric allografts suspected to have either severe rejection or thrombosis of the renal vein or artery. METHODS: From July 1990 to August 1994 the grafts of 15 out of a total of 315 patients were vitally threatened. Technetium-99m DTPA scintigraphy and color coded Duplex sonography were performed in all patients. For scintigraphic evaluation of transplant perfusion analog scans up to 60 min postinjection, and time-activity curves over the first 60 sec after injection of 370-440 MBq Tc-99m diethylenetriaminepentaacetate acid (DTPA) were used and classified by a perfusion score, the time between renal and iliac artery peaks (TDiff) and the washout of the renogram curve. Additionally, evaluation of excretion function and assessment of vascular or urinary leaks were performed. By color coded Duplex sonography the perfusion in all sections of the graft as well as the vascular anastomoses were examined and the maximal blood flow velocity (Vmax) and the resistive index (RI) in the renal artery were determined by means of the pulsed Doppler device. Pathologic-anatomical diagnosis was achieved by either biopsy or post-explant histology in all grafts. RESULTS: Scintigraphy and color coded Duplex sonography could reliably differentiate minimal (8/15) and not perfused (7/15) renal allografts. The results were confirmed either by angiography in digital subtraction technique (DSA) or the clinical follow up. CONCLUSION: In summary, perfusion scintigraphy and color coded Duplex sonography are comparable modalities to assess kidney graft perfusion. In clinical practice scintigraphy and color-coded Doppler sonography can replace digital subtraction angiography in the evaluation of minimal allograft perfusion.

Thyroid autonomy with color-coded image-directed Doppler sonography: internal hypervascularization for the recognition of autonomous adenomas.

In a prospective study, we assessed the possibility of recognizing autonomous adenomas of the thyroid with color-coded image-directed Doppler sonography using internal hypervascularization in thyroid nodules for identification. Fifty-three patients with thyroid nodules underwent additional CCDS examination and nuclear scintigraphy (reference). Of 29 patients having autonomous adenomas, 28 patients presented internal hypervascularization in their nodules resulting in a sensitivity of 96% and a specificity was 75%. Interestingly CCDS detected six adenomas in patients showing normal laboratory data (bTSH, TT3, FT4). CCDS could be used to exclude focal adenomas with a negative predictive value of 94%. The positive predictive value for adenoma was 82%.

Therapy with CD7 monoclonal antibody TH-69 is highly effective for xenografted human T-cell ALL.

Human T-cell acute lymphocytic leukaemia (ALL) was established in athymic nude or severe combined immunodeficient (SCID) mice by injecting CEM or MOLT-16 cells. When nude mice bearing approx. 2 g of tumour were treated with a single injection of CD7 antibody TH-69, 82.6% reached complete remission within 10 d whereas 13.0% showed partial remission. Similarly, in SCID mice with advanced disease a significant prolongation of survival was seen. The therapeutic effects were dependent upon dose and affinity of the antibody. TH-69 is a high-affinity antibody (7.6 x 10(9) M-1) that rapidly induced modulation during treatment. The Fc-portion of the antibody was required for effective tumour cell killing. Complement deposition was found on tumour sections after TH-69 treatment and in part may account for tumour destruction. There was no evidence for antibody-dependent cellular cytotoxicity (ADCC). The kinetics of tumour disappearance suggested the initiation of a programmed cell death (PCD), despite the lack of significant DNA fragmentation. Unmodified high-affinity antibodies to the T-cell antigen CD7 have potential for T-cell ALL therapy.

Reduction of renal uptake of monoclonal antibody fragments by amino acid infusion.

UNLABELLED: The renal uptake of radiolabeled antibody fragments and peptides presents a problem in radioimmunodetection and therapy, compromising lesion sensitivity, especially with intracellularly-retained isotopes. Previously, we showed that cationic amino acids and their derivatives are capable of significantly reducing kidney uptake in animals. We report our initial clinical results of successful renal uptake reduction in five patients who underwent cancer radioimmunodetection with 99mTc-anti-CEA Fab' fragments. METHODS: The patients were infused with two liters of a commercially-available nutritive amino acid solution (containing approximately 2.25 g/liter lysine-glutamate and 2.50 g/liter arginine), whereas 75 control patients received the same volume of saline (quantification of organ and tumor kinetics from conjugate whole-body views by ROI technique). RESULTS: The renal uptake in the amino acid group was significantly lower (p<0.05) than in the control group (11.1 +/- 2.0% injected dose versus 17.7 +/- 7.0% injected dose at 24 hr postinjection), whereas the uptake of all other organs remained unaffected. Gel filtration chromatography of the urine taken from amino-acid-treated patients showed that a significantly higher amount of excreted activity was bound to intact Fab' (53% of excreted activity) in contrast to only less than 10% in the control group. CONCLUSION: The renal uptake of monoclonal antibody fragments in patients can be reduced significantly by amino acid infusion, even at considerably lower doses than those that were safe and effective in animals. As was found in animals, the mechanism seems to rely on an inhibition of the re-absorption of tubularly-filtered proteins by the proximal tubule cells. These results encourage further clinical trials to lower the renal uptake experienced in radioimmunodetection, as well as in therapeutic trials with antibody fragments and peptides.

Diagnostic accuracy and tumor-targeting kinetics of complete versus fragmented 99mTc-labeled anti-carcinoembryonic antigen antibodies: an intraindividual comparison.

The goal of this study was to intraindividually compare a complete versus a fragmented, directly 99mTc-labeled, monoclonal anti-carcinoembryonic antigen (CEA) antibody, with respect to their antigen-targeting kinetics, sensitivity, and diagnostic accuracy in patients with CEA-expressing tumors. Twenty-five patients were investigated with the 99mTc-labeled anti-CEA IgG1 BW 431/26 and the F(ab')2/Fab' fragment mixture F023C5 within 7 days. For quantitative analysis, the region of interest technique was applied to planar scans, whole-body scans, and single photon emission computed tomography slices 10 min to 48 h postinjection (PI). Final correlations were performed according to the histopathology after surgery or biopsy. Earliest tumor detection was possible with complete IgG1 4 h PI (52% of finally positive lesions). Twenty-four- or even 48-h scans were necessary in 48% of finally positive lesions; tumor detection with fragments was possible in 17% at 1 h PI and in 94% at 4 h PI. With both monoclonal antibodies, in 35%, single photon emission computed tomography was necessary for tumor detection. Absolute antibody uptake in tumor lesions was higher with complete monoclonal antibodies than with fragments. The sensitivity of fragments was higher in detecting primary tumors, local recurrences, and lymph node metastases. For detection of liver metastases, sensitivity was also higher for fragments than for IgG (87 versus 73%), but in scintigraphically positive lesions, tumor:background ratios were significantly lower with fragments (1.26 +/- 0.12 versus 1.70 +/- 0.32; P < 0.01). Therefore, fragments seem to be more suitable for earlier detection of lesions known for their good vascularization, vascular permeability, and antigen accessibility, such as local recurrences, lymph node metastases, and peritoneal carcinomatoses. In liver metastases (high interstitial pressure, low vascular leakage), sensitivity of fragments is higher, but their rapid serum and whole-body clearance lead to a lower absolute antibody uptake, with the consequence of significantly lower tumor:background ratios than with IgG.

Reduction of the renal uptake of radiolabeled monoclonal antibody fragments by cationic amino acids and their derivatives.

The renal uptake of radiolabeled antibody fragments and peptides is a problem in radioimmunodetection and radioimmunotherapy, especially with intracellular retained radiometals. The aim of this study was to develop suitable methods to reduce this kidney uptake. BALB/c mice or nude mice bearing the human GW-39 colon carcinoma xenograft were given i.p. injections of basic amino acids or a range of different basic amino acid derivatives, amino sugars, as well as cationic peptides. The effect of these agents on the biodistribution of Fab' and F(ab')2 fragments of different mAbs radiolabeled with 99mTc, 188Re, 111In, 88Y, or 125I was studied. Tumor and organ uptake was determined and compared to untreated mice. The kidney uptake of Fab' fragments was reduced 5-6-fold in a dose-dependent manner as compared to untreated controls. The uptake in all other organs, as well as the tumor, was unaffected. A similar reduction in renal retention was seen for all other intracellularly retained isotopes, as well as for F(ab')2 fragments. D- and L-isomers of lysine were equally effective whether given i.p. or p.o. D-glucosamine was effective, but its N-acetyl derivative was not. Basic polypeptides (e.g., poly-L-lysine) were also effective; their potency increased with increasing molecular weight. HPLC of the urine taken from treated animals showed the excretion of intact Fab', in contrast to mostly low-molecular-weight metabolites in the control group. These studies indicate that a variety of basic compounds is capable of inhibiting the tubular reabsorption of peptides and proteins, thus lowering the kidney uptake of antibody fragments significantly. On a molecular basis, the effect seems to essentially rely on the presence of a positively charged amino group. By reducing renal retention of antibody fragments, their role as imaging and therapeutic agents may be expanded.

Comparison of complete versus fragmented technetium-99m-labeled anti-CEA monoclonal antibodies for immunoscintigraphy in colorectal cancer.

UNLABELLED: The goal of this study was to intraindividually compare complete versus fragmented directly labeled 99mTc monoclonal anti-CEA antibody with respect to antigen targeting and tumor uptake kinetics, sensitivity and diagnostic accuracy in colorectal cancer patients. METHODS: Twenty-five patients were investigated with 99mTc-labeled anti-CEA IgG1 BW 431/26 and the F(ab')2/Fab' fragment mixture F023C5 within 7 days. For quantitative analysis, an ROI technique was applied to planar scans, whole-body scans and SPECT slices 10 min to 48 hr postinjection. Final correlations were performed according to histology after surgery or biopsy. RESULTS: Earliest tumor detection with complete IgG1 was possible 4 hr postinjection (52% of finally positive lesions); imaging at 24 hr or even 48 hr was necessary in 48%. Tumor detection with fragments was possible in 17% at 1 hr postinjection and in 94% at 4 hr postinjection. In 35%, SPECT was necessary for tumor detection with both MAbs. Absolute antibody uptake in tumor lesions was higher with complete MAbs than with fragments. CONCLUSIONS: Lesions known for their good vascularization, vascular permeability and antigen accessibility were detected earlier and with higher sensitivity with fragments than with complete MAbs due to faster background clearance despite lower absolute antibody uptake.

Is there still a need for Tc-99m DMSA renal imaging?

Scintigraphy with Tc-99m MAG3 is, to date, the most commonly used technique for evaluating separate renal function (SRF). In this study, the performance of this technique is compared to Tc-99m DMSA. A total of 37 patients with various kidney disorders (12 children and 25 adults) underwent both Tc-99m DMSA and Tc-99m MAG 3 scintigraphy. In children and adults of normal weight the correlation coefficient between the two methods was 0.99 (P < 0.001), whereas in individuals who were more than 10% overweight according to Broca, or who had abnormal anatomical positions of the kidneys, the correlation coefficient was 0.82 (P < 0.05). Scintigraphy with Tc-99m DMSA was more accurate in renal parenchyma lesions. These results indicate that Tc-99m DMSA scintigraphy is preferable for the evaluation of SRF in patients who are more than 10% overweight, or have abnormal positions of the kidneys.

Perfusion scintigraphy and color-coded duplex sonography in a minimally perfused renal allograft.

Both, 99mTc DTPA perfusion scintigraphy and color-coded duplex sonography are reliable methods to quantitatively and qualitatively assess kidney transplant perfusion. In this case, minimal perfusion could be detected in a kidney allograft with marked vascular rejection by the scintigraphic analogous scan, whereas color-coded duplex sonography failed.

99mTc-labelled anti NCA-95 antibodies in prosthetic heart valve endocarditis.

A 54-y old women with earlier replacement of the mitral and aortic valves and clinical signs of localized endocarditis was studied with 99mTc-labelled anti NCA-95 antibody. Whereas echocardiographic findings were negative, increased radionuclide uptake was observed left parasternal over the mitral valve as a sign of prosthetic valve endocarditis. This result could be confirmed by a similar study with leukocytes labelled in vitro with 111In-oxine.