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Biomedical subjects

C Decristoforo

Publications and source records attributed to C Decristoforo.

24 records · Page 2Linked to original sources
PubMed1994

Technetium-99m human immunoglobulin scintigraphy in psoriatic arthropathy: first results.

Standard bone scintigraphy [using technetium-99m methylene diphosphonate (MDP)] is widely held to be the most sensitive method for the early detection of psoriatic arthropathy. Preliminary results of this study reveal that 99mTc human immunoglobulin (HIG) scintigraphy demonstrates a typical premature pattern of extradermal psoriatic disease in digits indicative of the early stage of psoriatic arthritis. This pattern was also found in a rare case of psoriatic arthropathy without skin lesions. 99mTc-HIG scintigraphy appears to reveal the initial inflammatory characteristics of later bone lesions. In the advanced stage of psoriatic arthritis, 99mTc-MDP and 99mTc-HIG scans were found to be equally sensitive in the detection of the affected joints. Thus 99mTc-HIG scintigraphy seems to be useful in the early detection of psoriatic arthropathy and also in advanced psoriatic arthritis, as well as for the detection of psoriatic arthropathy without skin lesions.

Arthritis, Psoriatic↗
PubMed1993

A simple two-strip method to determine the radiochemical purity of technetium-99m mercaptoacetyltriglycine.

Technetium-99m mercaptoacetyltriglycine (MAG3) has been used extensively as a renal function agent for several years. Radioimpurities in the MAG3 kit preparation are not only concentrated and excreted in the kidneys. Therefore proper quality control for renal studies is even more important to make possible a rapid and adequate interpretation of diagnostic studies. The standard method to determine the radiochemical purity is high-performance liquid chromatography (HPLC), which is time consuming and expensive. We set up a new simple thin-layer chromatography (TLC) method based on instant thin-layer silica gel strips as stationary phase for checking the main impurities, free pertechnetate and reduced hydrolysed 99mTc-colloid. Comparison of TLC and HPLC results showed no significant differences (t-test, P < 0.05); the correlation between the results obtained with the two methods in respect of the free pertechnetate content was excellent (r = 0.99913). The TLC method was also efficient in determining the percentage of 99mTc-colloid. The main impurity found in 37 routine preparations was free pertechnetate; the mean radiochemical purity was 97.95%. The time required to perform the analysis was less than 20 min. The new TLC system is a cheap, simple, fast, reliable and accurate method for the quality control of the MAG3 kit preparation, and is especially suitable for routine use.

Chromatography, High Pressure Liquid↗
PubMed1993

[Quality control of radiopharmaceuticals from the clinical aspect--a necessity?].

Radiopharmaceuticals are a special group of drugs since many are eventually prepared in the hospital and the nuclear medicine department is responsible for meeting quality criteria such as sterility, radionuclide, radiochemical and chemical purity of these drugs. We tested 266 preparations of 14 different radiopharmaceuticals from commercial kits for their radiochemical purity. Only four compounds showed deficiencies in labelling (anti-granulocyte MAb, HIG, HMPAO, MAG3, altogether 18 preparations). All of them were 99mTc-pharmaceuticals with a relatively low tin content of the kit. The reasons for the poor quality of these products could be found. This study shows the importance of a good quality control system (including other tests like sterility and environmental monitoring) to guarantee the safety and efficacy of radiopharmaceuticals prepared in the hospital.

Humans↗
PubMedDate not supplied

99mTc-labeling and in vitro and in vivo evaluation of HYNIC- and (Nalpha-His)acetic acid-modified [D-Glu1]-minigastrin.

Gastrin/CCK-2 receptors are overexpressed in a number of tumors such as medullary thyroid cancer (MTC) and small cell lung cancer (SCLC). Recently [D-Glu1]-minigastrin (MG) has been radiolabeled with 131I, 111In, and 90Y and evaluated in patients. This study describes the labeling and evaluation of MG with technetium-99m using two different labeling approaches: HYNIC as bifunctional coupling agent and (Nalpha-His)Ac as tridentate ligand for 99mTc(CO3) labeling. Labeling was perfomed at high specific activities using Tricine and EDDA as coligands for HYNIC-MG and [99mTc(OH2)3(CO)3]+ for (Nalpha-His)Ac-MG. Stability experiments were carried out by reversed phase HPLC analysis in PBS, serum, histidine, and cysteine solutions, as well as rat liver and kidney homogenates. Receptor binding and internalization experiments were performed using CCK-2 receptor positive AR42J rat pancreatic tumor cells. Biodistribution experiments were carried out in nude mice carrying AR42J tumors by injection of 99mTc-labeled peptide with or without coinjection of 50 microg of minigastrin I human (MGh). HYNIC-MG and (Nalpha-His)Ac-MG could be radiolabeled at high specific activities (>1 Ci/micromol). For HYNIC-MG, high labeling yields (>95%) were achieved using Tricine and EDDA as coligands. Stability experiments of all 99mTc-labeled conjugates revealed a high stability of the label in PBS and serum as well as toward challenge with histidine and cysteine. Incubation in kidney homogenates resulted in a rapid degradation of all conjugates with <10% intact peptide after 60 min at 37 degrees C, with no considerable differences between the radiolabeled conjugates; a somewhat lower degradation rate was seen in liver homogenates. Protein binding varied considerably with lowest levels for 99mTc-EDDA/HYNIC-MG. Competition experiments of unlabeled conjugates on AR42J membranes versus [125I-Tyr12]-gastrin I showed high CCK-2 receptor affinity for all conjugates under study. Internalization behavior was very rapid for all radiolabeled conjugates in the order of 99mTc-(Nalpha-His)Ac-MG > 99mTc-EDDA/HYNIC-MG > 99mTc-Tricine/HYNIC-MG. In tumor-bearing nude mice the highest tumor-uptake was observed with 99mTc-EDDA/HYNIC-MG (8.1%ID/g) followed by 99mTc-Tricine/HYNIC-MG (2.2%ID/g) and 99mTc-(Nalpha-His)Ac-MG (1.2%ID/g) which correlated with kidney uptake (101.0%ID/g, 53.8%ID/g, 1.8%ID/g respectively). In this series of compounds 99mTc-EDDA/HYNIC-MG with its very high tumor/organ ratios except for kidneys seems to be the most promising agent to target CCK-2 receptors. Despite promising properties concerning receptor binding, internalization, and in vitro stability, 99mTc-(Nalpha-His)Ac-MG showed low tumor uptake in vivo.

Acetates↗
PubMedDate not supplied

Preparation, 99mTc-labeling, and in vitro characterization of HYNIC and N3S modified RC-160 and [Tyr3]octreotide.

The synthesis of conjugates of two somatostatin analogues, RC-160 and [Tyr3]octreotide with different bifunctional chelators for labeling with Tc-99m, is described. Conjugates with hydrazinonicotinamide (HYNIC) and two N3S compounds (benzoyl MAG3 and a N3S adipate derivative) were prepared on a small scale with high purity allowing evaluation of different bifunctional chelators on the same peptide without extensive peptide synthesis. High in vitro stability and retained binding affinity was found for all conjugates except for the N3S adipate. Peptide conjugates could be labeled at high specific activities (>1 Ci/micromol) with 99mTc, and different coligands were explored for the HYNIC conjugates. The resulting radiolabeled complexes were highly stable and showed binding affinity to somatostatin receptors in the nanomolar range. Varying labeling yield, stability, lipophilicity, and isomerism were found for different coligands used for labeling HYNIC conjugates, with lower lipophilicity, higher stability, and fewer coordination isomers for EDDA and tricine/nicotinic acid as ternary coligand compared to tricine. In particular, HYNIC complexes showed promising results for further in vivo evaluation.

Animals↗