International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology最新文献

After demonstrating enhanced tumor cell binding with a mixture of monoclonal antibodies (MAbs) in vitro, biodistribution and immunoscintigraphy studies with 3 radioiodinated anti-colon cancer MAbs and a non-specific control MAb (MOPC) were conducted in a human colon cancer (GW-39)-hamster model system. Each of the specific MAbs, but not MOPC, demonstrated extensive tumor binding and in scintigrams affected visualization of all large tumors (>0.85 g) over background. Using single MAbs, few small tumors (0.19–0.50 g) were defined above background (0–29%). However, with combinations of these specific MAbs small tumors were more frequently defined in scintigrams (43–67%). Radioimages using higher doses of MAbs and small, younger tumors more clearly demonstrated the superiority of a MAb mixture. These results confirmed that combinations of MAbs to different antigens can detect smaller tumors with better tumor localization when compared to component MAbs used singly. This study supports the concept that tumor targeting and detection may be enhanced with appropriate mixtures of MAbs.

The use of internal-surface reversed-phase (ISRP) chromatography of unprocessed plasma samples was investigated as an alternative method of quantitation of the arterial plasma metabolite time course of [^18F]N-methylspiperone. The ISRP method was directly compared to standard solid phase extraction/HPLC (SPE/HPLC) methods currently in wide use. Results indicate that: (1) the ISRP method is rapid and minimizes sample preparation; (2) recovery of radioactivity from the ISRP column is > 90%; (3) no radioactivity remains associated with chromatographically size excluded proteins and (4) the quantitative results are well correlated with conventional SPE/HPLC methods.

Tc-99m monocationic mixed ligand complexes of phenyl substituted/condensed Schiff's bases, N,N′-ethylene-bis-(benzoylacetone imine) (L_b) or N,N′-ethylene-bis-(salicylaldehyde imine) (L_c) or N,N′-ethylene-bis-(2-hydroxyacetophenone imine) (L_d) and trimethylphosphine were synthesized to determine the influence of the presence of a phenyl group in these tracers on their heart uptake in rats. A new formulation procedure using aq. β-hydroxypropylcyclodextrin (HPB) solution was developed for intravenous administration of nonpolar ^99mTc complexes. Comparison of biodistribution data for the reference ^99mTc complex from N,N′-ethylene-bis-(acetylacetone imine) and trimethylphosphine using HPB formulation and alternate formulation (0.9% saline) showed the same results. Biodistribution of the title ^99mTc complexes, [^99mTc L_b (PMe₃)₂]⁺, [^99mTc L_c (PMe₃)₂]⁺ and [^99mTc L_d (PMe₃)₂]⁺ showed heart-to-blood activity ratios of 1.7, 2.1 and 1.7, respectively, at 15 min post-injection in rats.

The availability of clorgyline for regional monoamine oxidase-A (MAO-A) determination was examined using [¹⁴C]clorgyline in rat. [¹⁴C]Clorgyline was synthesized by the methylation reaction of N-desmethylclorgyline and [¹⁴C]methyliodide in dimethylformamide with high radiochemical yield. The MAO-A distribution map by autoradiography correlated with that by histochemical technique and its quantity was consistent with the calculated MAO-A amount based on previous reports. The combination of labeled clorgyline and autoradiographic technique will promise the quantitative measurement of regional MAO-A distribution.

A triglyceride analog, glycerol-2-palmitoyl-1,3-di-15-(p-iodophenyl)pentadecanoate (DPPG) was synthesized and radiolabeled for evaluation as a potential functional liver scintigraphic agent. Uptake of DPPG was compared in normal, diabetic, tumor-bearing and heparin pretreated rats, revealing differences in uptake and clearance of radioactivity, correlating with hepatic lipase activity of these groups. Similar results were observed by γ -camera scintigraphy. Comparing the uptake of DPPG with that of its fatty acid component, 15-(p-iodophenyl)pentadecanoic acid (IPPA), revealed that the peak uptake of IPPA in the liver was about half that of DPPG. Based upon these findings, DPPG warrants further study as a hepatic radiodiagnostic agent.

The in vitro labeling and stability of ^99mTc-labeled antibody Fab′ fragments prepared by a direct labeling technique were evaluated. Eight antibody fragments derived from murine IgG1 (N = 5), IgG2a (N = 2) and IgG3 (N = 1) isotypes were labeled with a preformed ^99mTc-d-glucarate complex. No loss of radioactivity incorporation was observed for all the ^99mTc-labeled antibody fragments after 24 h incubation at 37 °C. The ^99mTc-labeled antibody fragments (IgG1, N = 2; IgG2a, N = 2; IgG3, N = 1) were stable upon challenge with DTPA, EDTA or acidic pH. Furthermore, using the affinity chromatography technique, two of the ^99mTc-labeled antibody fragments displayed no loss of immunoreactivity after prolonged incubation in phosphate buffer up to 24 h at 37 °C. The bonding between ^99mTc and antibody fragments was elucidated by challenging with a diamide ditholate (N₂S₂) compound. The Fab′ with IgG2a isotype displayed tighter binding to ^99mTc in comparison to the Fab′ from IgG1 and IgG3 isotype in N₂S₂ challenge and incubation with human plasma. The in vivo biodistribution of five ^99mTc-labeled fragments were evaluated in normal mice. In conclusion, the direct labeling method allows stable ^99mTc labeling of antibody fragments from three of the major murine isotypes.

In the present in vivo study the uptake kinetics of radioiodinated albumin were determined in normal organs, and tumours of rats using sequential scintigraphy. Rat serum (RSA) was radioiodinated either directly at a tyrosine residue (d-RSA), or indirectly at a residualizing marker tagged to the albumin (rm-RSA). These labelling procedures did not alter the kinetics of labelled albumin, as shown by blood disappearance curves. Directly labelled albumin was shown to have tumour uptake. Residualizing markers like tyramine-cellobiose (TCB), tyramine-deoxysorbitol (TDS) and aminonaphthaltyrimide-deoxysorbitol (ANTDS) are metabolically inert. After the intracellular degradation of the albumin carrier the TCB-, TDS- and ATNDS-residues accumulate in the lysosomes, particularly those of tumour cells. It was able to be demonstrated that residualizing-marker tagged albumin-bound radioactivity was five times higher after 72 h than the tumour radioactivity after use of directly labelled RSA. These data found support when whole-body retention of directly labelled RSA, and residualizing marker-RSAs, were determined. After 72 h, 60% of ¹³¹I bound to RSA directly had been excreted, compared to only 25% of the activity attached indirectly to RSA with a residualizing marker. Whole-body autoradiography of rats injected with directly labelled RSA, or residualizing marker-RSA, support these results. Most of the radioactivity of directly labelled RSA was excreted within 24 h, whereas labelled residualizing marker-RSAs were also stored in tumour and liver tissue. ANTDS bound to RSA allows fluorescence microscopy. Cryosections of tumours from rats preinjected 10 min and 24 h with ANTDS-RSA before dissection, demonstrated that the fluorescence is localized on and in tumour cells. This indicates that cellular uptake of the marker takes place. Fluorescence was not observed in muscle tissue. This appears to suggest that the albumin uptake is greater in tumours than in normal tissue, and that it is metabolized in the tumour cells.