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S J Mather

Publications and source records attributed to S J Mather.

At least 37 records · Page 2Linked to original sources
PubMed2000

Photoreduction of monoclonal antibodies for conjugation and fragmentation.

The conjugation of enzymes, fluorescent or radioactive labels, cross-linkers and other moieties to antibodies is a commonly performed procedure in biochemical research. Using reduced disulphides, conjugation can be an inconvenient, multistep, time- and material-consuming process. We have developed a reduction technique based on UV irradiation, which lacks these drawbacks. Antibodies are irradiated in a sealed vial for a few minutes by a common laboratory UV source in the presence of stannous ions, following the depletion of atmospheric oxygen. The preparation may subsequently be conjugated with thiol-reactive probes such as maleimide derivatives, with no need for any prior purification or concentration. This simple, rapid and effective reduction and conjugation process results in a fully functional immunoglobulin conjugate that can be used for a variety of biochemical applications.

Animals↗
PubMed2000

Pharmacokinetics and renal handling of 99mTc-labeled peptides.

UNLABELLED: 99mTc-labeled peptides, particularly those of a lipophilic nature, are often excreted through the hepatobiliary system, and the subsequent accumulation in the intestine may obscure receptor-mediated uptake in tumor sites in the pelvis. We have therefore explored the route and rate of excretion of a small series of Tc-labeled peptides to shed some light on the mechanisms that influence the clearance of these agents. METHODS: Pharmacokinetic parameters, biodistribution, routes of elimination of 99mTc-complexes of 3 model tetrapeptides--namely, acetyl-N-Gly-Gly-Cys-Gly (AGGCG), acetyl-N-Ser-Ser-Cys-Gly (ASSCG), and acetyl-N-Gly-Gly-Cys-Lys (AGGCL)--were determined in rats in vivo. Renal handling of the complexes was studied in the perfused rat kidney. RESULTS: After intravenous injection, a relatively fast disappearance of the complexes from blood was found. Although the parameters of distribution in all 3 chelates were very similar, the elimination rate of 99mTc-AGGCG was higher than those of 99mTc-ASSCG and 99mTc-AGGCL. The Tc complexes under study were distributed mainly to the excretory organs (kidneys and liver), and no specific accumulation in other organs or tissues was found. Most of the radioactivity after intravenous administration of the chelates was rapidly eliminated through the urine, but a significant amount was also excreted through the feces, in the following order among the 3 chelates: 99mTc-AGGCL < 99mTc-ASSCG < 99mTc-AGGCG. Different proportions of glomerular filtration and secretion in renal tubules of the complexes were found in the perfused rat kidney. Elimination by glomerular filtration was dominant only in the case of 99mTc-AGGCL, whereas the rate of filtration of 99mTc-AGGCG was very low because of its high protein binding. Various rates of secretion into renal tubules were shown for all 3 agents. This renal excretion pathway was decisive in 99mTc-AGGCG and lowest in 99mTc-AGGCL. 99mTc-ASSCG was eliminated by both mechanisms at similar rates. CONCLUSION: These studies show that increasing the hydrophilic nature or reducing the negative charge of the peptides will reduce their hepatobiliary excretion, whereas the incorporation of suitable peptide sequences permits them to exploit efficient routes of renal excretion, such as tubular secretion, thereby optimizing the pattern of biodistribution of these radiopharmaceuticals.

Animals↗
PubMed2000

99mTc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-receptor-positive tumors: preclinical evaluation and comparison with 111In-octreotide.

UNLABELLED: In this paper we describe the preclinical evaluation of 99mTc-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) using different coligands for radiolabeling and a comparison of their in vitro and in vivo properties with 111In-diethylenetriaminepentaacetic acid (DTPA)-octreotide. METHODS: HYNIC-TOC was radiolabeled at high specific activities using tricine, ethylenediaminediacetic acid (EDDA), and tricine-nicotinic acid as coligand systems. Receptor binding was tested using AR42J rat pancreatic tumor cell membranes. Internalization and protein binding studies were performed, and biodistribution and tumor uptake were determined in AR42J tumor-bearing nude mice. RESULTS: All 99mTc-labeled HYNIC peptides showed retained somatostatin-receptor binding affinities (Kd < 2.65 nM). Protein binding and internalization rates were dependent on the coligand used. Specific tumor uptake between 5.8 and 9.6 percentage injected dose per gram (%ID/g) was found for the 99mTc-labeled peptides, compared with 4.3 %ID/g for 111In-DTPA-octreotide. Tricine as coligand showed higher activity levels in muscle, blood, and liver, whereas tricine-nicotinic acid produced significant levels of activity in the gastrointestinal tract. EDDA showed the most promising overall biodistribution profile, with tumor-to-liver and tumor-to-gastrointestinal tract ratios similar to those obtained with 111In-DTPA-octreotide, lower ratios in blood and muscle, but considerably higher tumor-to-kidney ratios. CONCLUSION: TOC can be radiolabeled to high specific activities using HYNIC as a bifunctional chelator. The high specific tumor uptake, rapid blood clearance, and predominantly renal excretion make 99mTc-EDDA-HYNIC-TOC a promising candidate for an alternative to 111In-DTPA-octreotide for tumor imaging.

Animals↗
PubMed1999

Technetium-99m somatostatin analogues: effect of labelling methods and peptide sequence.

In this paper the preclinical evaluation of the somatostatin analogue RC160 labelled with technetium-99m using bifunctional chelators (BFCs) based on the hydrazinonicotinamide (HYNIC) and N(3)S system is described and a comparison made with [Tyr(3)]-octreotide (TOC). Conjugates of both peptides with HYNIC, and of RC160 with benzoyl-MAG(3) and an N(3)S-adipate derivative were prepared and radiolabelling performed at high specific activities using tricine, tricine/nicotinic acid and ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligands for HYNIC conjugates. All conjugates and (99m)Tc-labelled peptides showed preserved binding affinity for the somatostatin receptor (IC50, Kd<5 nM). The biodistribution was markedly dependent on the BFC and co-ligand used, with the amidothiol ligands showing a greater degree of hepatobiliary clearance, the HYNIC/tricine complex higher blood levels and the HYNIC/EDDA complex the highest level of renal excretion and lowest blood levels. All peptide conjugates showed receptor-mediated uptake in tumour xenografts, but tumour uptake was significantly lower for the (99m)Tc-RC160 derivatives compared with (99m)Tc-EDDA/HYNIC-[Tyr(3)]-octreotide (0.2%-3.5%ID/g vs 9.7%ID/g) and correlated well with the reduced internalisation rate for RC160 derivatives. Our results show that the selection of the labelling approach as well as the right choice of the peptide structure are crucial for labelling peptides with (99m)Tc to achieve complexes with favourable biodistribution. Despite the relatively low tumour uptake compared with (99m)Tc-EDDA/HYNIC-[Tyr(3)]-octreotide, (99m)Tc-RC160 could play a role in imaging tumours that do not bind octreotide derivatives.

Animals↗
PubMed1999

Humanisation and characterisation of PR1A3, a monoclonal antibody specific for cell-bound carcinoembryonic antigen.

Carcinoembryonic antigen (CEA) is highly expressed by most tumours of gastrointestinal origin, but its use as a target for tumour therapy is complicated by the high levels of soluble CEA that are found circulating in the blood of cancer patients. A monoclonal antibody PR1A3 has been prepared, which binds preferentially to cell-surface rather than soluble CEA, this cell selectivity should make PR1A3 an ideal candidate for antibody-targeted tumour therapy. PR1A3 has been humanised and shown to retain its cell-surface specificity and affinity. Stable expression of the humanised antibody from chinese hamster ovary (CHO) cells has been achieved after transfection and amplification. Since PR1A3 binds preferentially to cell-associated CEA, a cell-free enzyme-linked immunosorbent assay (ELISA) has been developed to allow characterisation and routine assay of the antibody. This assay was developed using a recombinant chimeric protein constructed by cloning the domain of CEA that is bound by PR1A3 (the B3 domain) into a hybrid gene containing the Fc portion of IgG and three domains of biliary glycoprotein. Stable expression of this hybrid protein has been achieved from CHO cells. In ELISA both humanised and murine PR1A3 bound strongly to this antigen but only at a minimal level to soluble CEA. Two binding sites for the antibody were found on the gastric carcinoma cell line MKN45, one of higher affinity (1 nM) and the other at lower affinity (60 nM). Similar affinities were found for both murine and humanised antibodies. The data presented make it unlikely that the differential binding to cell-surface as distinct from soluble CEA can be accounted for by low affinity of PR1A3 for CEA, and provides further support for the hypothesis that some conformational change takes place on CEA release from cells and that it is this change that blocks PR1A3 binding to its epitope.

Amino Acid Sequence↗
PubMed1999

99m-Technetium-labelled peptide-HYNIC conjugates: effects of lipophilicity and stability on biodistribution.

The aim of this study was to explore the effects of lipophilicity and stability on the biodistribution of 99mTc labelled peptides through the use of different co-ligands. 6-Hydrazinopyridine-3-carboxylic acid (HYNIC) was coupled to the somatostatin analogue RC160 and radiolabelled using a range of ethylendiaminediacetic acid (EDDA) and ethylenediaminetetraacetic acid (EDTA) derivatives as well as tricine and pyridine/tricine as co-ligands. After labelling with technetium-99m, chromatographic, stability, protein-binding, and rat biodistribution studies were performed. For most co-ligands, biodistribution correlated well with in vitro properties. Lipophilic substitution on EDDA resulted in higher protein binding, increased liver uptake, and intestinal excretion. Stabilisation of tricine with pyridines reduced blood levels and lowered liver uptake. EDTA derivatives showed high instability in vitro and in vivo.

Animals↗
PubMed1999

A survey of pre-operative fasting regimens before regional ophthalmic anaesthesia in three regions of the United Kingdom.

A postal and telephone survey of the practice of fasting before regional ophthalmic anaesthesia with and without sedation was sent to 50 hospitals in three regions of the United Kingdom. Responses were received from 100% of hospitals. In most hospitals (58%), local anaesthetic blocks were performed by both surgeons and anaesthetists, with surgeons alone providing ophthalmic anaesthesia in only 14%. Eighty-six per cent of hospitals surveyed had a formal policy regarding pre-operative fasting, with 44% allowing patients to eat and drink freely until their operation. In those hospitals where a fast was imposed, the most common fasting periods were 6 h for food and 2 h for fluids. Twenty-six per cent of respondents would be prepared to give intravenous sedation to a non-fasted patient during eye surgery: small doses of benzodiazepine were the most frequently suggested method. National evidence-based guidelines for ophthalmic regional anaesthesia are needed.

Anesthesia, Local↗
PubMed1998

99mTc-labelled SM3 in the preoperative evaluation of axillary lymph nodes and primary breast cancer with change detection statistical processing as an aid to tumour detection.

The extent of primary surgery for breast cancer could be tailored to the patient if previous information on the presence or absence of lymph node involvement could be reliably determined. Prospective radioimmunoscintigraphy in 29 patients with primary breast cancer that was found on screening has been undertaken with 555 MBq (15 mCi) 99mTc SM3, an Imperial Cancer Research Fund (ICRF) murine monoclonal antibody, 0.5 mg with images at 10 min and 22 h, and analysis using a change detection algorithm. Sites of significant change between the early and later images were displayed as a map of probabilities. Image-positive and -negative axillary lymph nodes were compared by histology in the 28 evaluable patients. The correct identification of the presence or absence of node involvement, even if impalpable, has been shown in 24 out of 28 patients (29 lymph node groups). Sensitivity was 90% (nine out of ten), specificity 84% (16 out of 19) and accuracy 86%. These results encourage further assessment of this technique.

Adult↗
PubMed1998

Onset of neuromuscular blockade and intubating conditions one minute after the administration of rocuronium in children.

In a blinded randomized study intubating conditions were compared at one min following intravenous induction with propofol and either suxamethonium 1.0 mg.kg-1, or rocuronium 0.6 mg.kg-1. Onset time to maximal twitch depression, % block at one minute and clinical duration (time to 25% recovery) were measured. Sixty children undergoing elective tonsillectomy were recruited. Onset time [42s (SD 11s)] and clinical duration [3.3 min (SD 1.0 min)] in the suxamethonium group was significantly (P < 0.001) less than in the rocuronium group [92s (41s)] and [24.2 min (6.6 min)] respectively. The median twitch height at one minute for suxamethonium was 0% (range 0-8%) and significantly greater (P < 0.001) at 5% (range 0-22%) for rocuronium. Despite this there was no difference in the intubating conditions at one minute with 25 excellent/5 good in the suxamethonium group and 27 excellent/3 good in the rocuronium group. We conclude that rocuronium 0.6 mg.kg-1 gives optimal intubating conditions at one minute in children.

Androstanols↗
PubMed1997

Site-specific conjugation and labelling of prostate antibody 7E11C5.3 (CYT-351) with technetium-99m.

Attachment of chelating agents to the sugar residues of antibodies for subsequent radiolabelling is an attractive approach since it may have less effect on the immunoreactivity than attachment through lysine residues, which are distributed throughout the antibody and may be present near the antigen binding site. We have attached a new hydrazide-linked chelator CYT-395 (Cytogen Corp., Princeton, N.J.) to the sugar residues of the anti-prostate monoclonal antibody 7E11C5.3 and optimised the conditions for labelling the conjugate with technetium-99m in order to compare the conjugate to 7E11C5.3 antibody labelled directly with technetium using a mercaptoethanol reduction technique. Labelling yields of 70%-90% were obtained at specific activities up to 2000 MBq/mg antibody. The stability of the technetium-labelled conjugate in plasma or to a challenge with 0.1 or 1.0 mM cysteine was similar to that of direct-labelled antibody. In nine patients with prostate cancer, the plasma clearance of the labelled conjugate followed a two-compartment model, with an average beta-phase half-life of 31.4+/-3.9 h. The average urinary clearance at 24 h was 15.3+/-5.0% of the injected dose. In this group of patients there was no significant difference between the blood and urine clearance of the labelled conjugate, and the clearances of the direct-labelled antibody.

Animals↗
PubMed1997

The development of technetium-99m-labelled interleukin-2: a new radiopharmaceutical for the in vivo detection of mononuclear cell infiltrates in immune-mediated diseases.

We describe here a new method for labelling interleukin-2 (IL-2) in high specific activity with 99mTc for in vivo studies in man. Labelling was performed via a two-step reaction using an N3S bifunctional chelating agent. To optimise the reaction, factors affecting the incorporation of 99mTc into the N3S ligand were studied. The conjugation of the preformed N3S chelate ligand to IL-2 was then similarly optimised. Various strategies for purifying the 99mTc-IL-2 were explored including size-exclusion, ion-exchange, and several modes of reversed-phase chromatography. The radiochemical purity of the purified protein was determined by HPLC, ITLC, TCA precipitation, and SDS-PAGE. The receptor binding capacity of 99mTc-IL-2 was studied. Biodistribution studies in normal mice were performed with 99mTc-IL-2 purified using different techniques or labelled after prolonged storage and compared to 125I-IL-2.

Animals↗
PubMed1997

Radiopharmaceuticals for the study of inflammatory processes: a review.

Recent advances in our understanding of the pathophysiology of inflammatory processes at the molecular level, combined with progress in radiopharmaceutical sciences, has boosted the development of nuclear medicine techniques for the diagnosis of infection/inflammation. The use of radiolabelled white blood cells has been studied and evaluated in several pathologies and is still the reference method. Several alternative approaches, however, have been developed that may, in the future, improve the specificity and the ease of use of the technique. For the first time, a radiopharmaceutical that may distinguish between sterile and septic inflammation, 99Tcm-Infecton, has been developed. Also, monoclonal antibody fragments, cytokines and a variety of new synthetic peptides that bind specifically to granulocytes have been prepared. Particularly promising appears to be the detection of the expression of adhesion molecules by activated endothelium as a first-line technique for the detection of inflammatory foci. For the diagnosis of autoimmunity and chronic inflammatory processes, important progress has also been made. Autoimmunity can now be studied by in vivo detection of tissue-infiltrating activated lymphocytes by radiolabelled interleukin-2. A radiopharmaceutical for the diagnosis of monocyte infiltration, J001X, is also available, and the commercially available Octreoscan holds promise in autoimmune and chronic inflammatory diseases. The efforts of the scientific community have given us new perspectives in diagnostic nuclear medicine: easier techniques that promise better sensitivity and specificity are now also being tested for the study of new disease conditions. The results of the clinical trials now in progress will determine the future of this challenging and fascinating field and the role of nuclear medicine in the management of patients with infection/inflammation.

Antibodies, Monoclonal↗
PubMed1997

Uptake of 99Tcm-nitrido dithiocarbamate complexes by tumour cells.

Uptake of radiopharmaceuticals by tumour cells may provide useful information on the biochemical characteristics of the cell, such as its drug resistance status. We have prepared a series of 99Tcm-nitrido dithiocarbamate complexes of the type [99TcmN(dtc)2] (dtc = N-R1-N-R2-dithiocarbamato, R1, R2 = Me, Me; Et, Et; Et, n-Bu; Me, CH2CH2NMe2; Me, CH2CH2NMe3+; Me, CH2COOMe), and investigated the kinetics of uptake of these complexes in several tumour cell lines. The 99Tcm-nitrido dithiocarbamate complexes were prepared by stannous reduction of [99Tcm]pertechnetate in a solution of DPTA and succinic dihydrazide followed by addition of the appropriate dithiocarbamate. The complexes were analysed by reverse-phase HPLC. The complexes were incubated with the human tumour cell lines MKN-45, H-69, H-348 and MCF-7 and with normal mixed leukocytes and erythrocytes, and the uptake and washout of the various complexes were determined at various time points. Uptake was rapid, high in some cell lines and lower in others. In general, the more lipophilic complexes showed high uptake, but the most lipophilic did not show the greatest uptake. Uptake was temperature-independent. Most of the bound activity was retained by the cells after removal of unbound tracer. The mechanism of uptake is different to that of 99Tcm-MIBI. The high and stable uptake of these complexes suggests that they may have application for in vivo tumour imaging and characterization, and further studies are required to establish their mechanisms of uptake.

Biological Transport, Active↗
PubMed1997

Imaging prostate cancer with technetium-99m-7E11-C5.3 (CYT-351).

UNLABELLED: To evaluate the performance of the 99mTc-labeled monoclonal antibody CYT-351 in visualizing prostate cancer, radioimmunoscintigraphy (RIS) was performed in 35 patients. METHODS: Antibody (0.5 mg) labeled with 600 MBq 99mTc was injected intravenously after obtaining informed consent. Planar and SPECT imaging was performed at 10 min and 6-8 and 22-24 hr postinjection. The scans were evaluated for visualization of the primary focus or local recurrence, extraprostatic invasion, lymph node involvement and uptake in bone and soft tissue metastases. RESULTS: Thirty-six studies in 35 patients were performed. In 13/14 evaluable studies with clinically localized prostate cancer, RIS had a true-positive rate of 92% (12/13). In eight patients with previous incidental carcinoma detected during transurethral resection undertaken for clinically benign disease, there were 86% true-positive results (6/7) and one true-negative result, which were confirmed by systematic needle biopsies. In six patients with evidence of local recurrence after a previous radical prostatectomy, the true-positive rate was 100% (6/6), which was confirmed by raised or rising prostate-specific antigen levels (PSA) and/or by biopsy. In the eight patients with known metastases, the disease was visualized in 4/4 with progression but not in the 3/3 with regression; one patient demonstrated regressing disease as determined by PSA levels. The overall accuracy was 92%. CONCLUSION: RIS with 99mTc CYT-351 is capable of providing good quality images and yielding clinically useful information safely. It has a potentially important clinical role for patients with rising PSA levels but negative images by conventional modalities.

Antibodies, Monoclonal↗
PubMed1996

Technetium-99m labelling of the anti-tumour antibody PR1A3 by photoactivation.

Irradiation of antibody with ultraviolet light leads to reduction of disulphide bonds. Thus irradiation can be used to generate free thiols prior to direct labelling of antibody with technetium-99m, and has a potential advantage over methods using chemical reducing agents such as mercaptoethanol or tin, in that no purification step is needed to remove excess reducing agent. We have used the photoactivation method developed by Sykes et al. to label the anti-tumour antibody PR1A3 with 99mTc. The antibody was irradiated at 300 nm using a Rayonet photochemical reactor with eight RMR3000 lamps. In a typical experiment, the antibody solution was injected into a nitrogen-filled borosilicate glass vial and purged with nitrogen. A degassed solution containing stannous fluoride and methylene diphosphonate was then added to the antibody and the vial was irradiated. Following the irradiation, [99mTc]pertechnetate was injected into the vial and the reaction mixture was incubated for 30 min at room temperature before being analysed by size-exclusion high-pressure liquid chromatography and instant thin-layer chromatography. Labelling yields greater than 95% were obtained using antibody concentrations ranging from 0.5mg/ml to 5mg/ml. Irradiation times as short as 5 min and tin to antibody ratios in the range between 11 and 32 microg tin per mg antibody gave high labelling yields. Labelling yields greater than 95% were obtained after storage of the photoactivated antibody at -70 degrees C for several weeks. The stability of the 99mTc-labelled photoactivated PR1A3 was similar to that of 99mTc-labelled mercaptoethanol-reduced PR1A3. The mean immunoreactive fraction was 77% for the photoactivation-labelled PR1A3, compared to 93% for PR1A3 labelled by mercaptoethanol reduction. Biodistribution studies were carried out using 99mTc-photoactivation-labelled PR1A3 or PR1A3 labelled by mercaptoethanol reduction in Balb/c mice and in nude mice with MKN-45 human tumour xenografts. There was no significant difference in tumour uptake between the mice that received photoactivated PR1A3 and those that received mercaptoethanol-reduced PR1A3. There was also no significant difference in uptake in most organs in Balb/c mice; however, the photoactivated antibody cleared more rapidly from the blood, and whole-body clearance was also faster for the photoactivated PR1A3. In conclusion, the photoactivation technique provides a very convenient "one-pot" method for labelling antibodies with 99mTc.

Animals↗
PubMed1996

Comparison of diclofenac and tenoxicam for postoperative analgesia with and without fentanyl in children undergoing adenotonsillectomy or tonsillectomy.

127 children scheduled for elective tonsillectomy or adenotonsillectomy were studied. Anaesthesia was induced with propofol and maintained with a volatile agent. At induction the child received either rectal diclofenac 1 mg.kg-1 with or without fentanyl 0.75 microgram.kg-1 i.v., or intravenous tenoxicam 0.4 mg.kg-1 with or without fentanyl 0.75 microgram.kg-1 i.v. Blood loss was measured peroperatively. Nausea and vomiting scores, sedation scores and pain scores were recorded in the recovery room, at one, two, four and eight h postoperatively and at discharge. There were no significant differences in blood loss between the groups or between nausea and vomiting scores. Pain scores in the tenoxicam without fentanyl group were significantly higher in recovery (P < 0.05) than the diclofenac group without fentanyl and both fentanyl groups. This group required supplemental analgesia earlier although this was not significant. The pain scores in the diclofenac with fentanyl group were significantly lower at one h and four h than the group receiving diclofenac alone (P = 0.008 and 0.02 respectively).

Adenoidectomy↗
PubMed1996

Prostatic radioimmunoscintigraphy: preliminary results using technetium-labelled monoclonal antibody, CYT-351.

OBJECTIVE: To investigate the clinical application of a new technique for imaging prostatic malignancy using planar imaging and single-photon emission tomography (SPET) with technetium-99m-labelled antibody to a prostatic cell surface membrane antigen. PATIENTS AND METHODS: Prostatic malignancy was imaged by radioimmunoscintigraphy (RIS) using a 99mTc-labelled monoclonal antibody, CYT-351, raised against a newly identified membrane antigen present in normal and malignant prostatic tissues. The protocol involved taking serial images and assessing the changes in activity, as the uptake of specific antibody increased with time and non-specific uptake decreased. Data from planar images were collected at 10 min, 6 and 24 h after injection with antibody, and by SPET at 6 and 24 h using a Siemens Orbiter Large Field of View gamma camera. Twenty-two RIS scans were evaluated, which included six patients with clinically localized disease, six patients with previous incidental carcinoma at prostatectomy for apparently benign disease, four patients with evidence of local recurrence after radical prostatectomy and six patients with metastatic disease. RESULTS: Primary tumours and secondary lymphatic and bone metastases were demonstrated. Only one minor side-effect was experienced. CONCLUSION: This RIS technique was capable of imaging primary prostatic malignancy and metastatic disease in lymph nodes and bone. Its clinical application remains to be defined, but potentially it provides a new means for tumour staging based upon tissue characterization. It may be particularly useful before radical prostatectomy and it is capable of imaging local recurrence following radical treatment of localized disease. Future applications include monitoring the progression of disease and the response to treatment.

Antibodies, Monoclonal↗