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M de Jong

Publications and source records attributed to M de Jong.

At least 19 recordsLinked to original sources
PubMed2007

Platelet and leukocyte activation in salvaged blood and the effect of its reinfusion on the circulating blood.

Postoperative wound drainage reinfusion reduces the frequency of homologous blood transfusion. The salvaged blood is depleted of coagulation factors but may contain platelets and leukocytes which are activated, and therefore potentially procoagulant. We ascertained the degree of activation of platelets and leukocytes in salvaged blood and asked whether their infusion produced any measurable effect on patients' coagulation system. We prospectively randomized 24 patients who had total knee arthroplasties to reinfusion of salvaged autologous blood (n = 12) or a standard drain with no reinfusion (n = 12). Analysis of the salvaged blood showed marked activation of platelets as shown by their expression of P-selectin, CD40 ligand, and Factor V/Va, and as increased numbers of platelet-derived microparticles. After reinfusion there was no measurable effect on activation markers of circulating platelets or leukocytes but there was a decrease in platelet count in the reinfused group compared with the control group. Levels of prothrombin fragment F1 + 2 (suggesting thrombin formation) increased in the reinfused group compared with control group, possibly indicating activation of coagulation systemically. The platelets and leukocytes in salvaged blood are markedly activated and their reinfusion causes a decrease in platelet count in the recipient and a possible increase in thrombin generation potentially favoring thrombosis.

Aged↗
PubMed2006

In vivo radionuclide uptake quantification using a multi-pinhole SPECT system to predict renal function in small animals.

PURPOSE: In vivo quantification of radiopharmaceuticals has great potential as a tool in developing new drugs. We investigated the accuracy of in vivo quantification with multi-pinhole single-photon emission computed tomography (SPECT) in rats. METHODS: Fifteen male Lewis rats with different stages of renal dysfunction were injected with 50 MBq 99mTc-dimercaptosuccinic acid. Four to six hours after injection, SPECT of the kidneys was acquired with a new four-headed multi-pinhole collimator camera. Immediately after imaging the rats were sacrificed and the kidneys were counted in a gamma-counter to determine the absorbed activity. SPECT data were reconstructed iteratively and regions of interest (ROIs) were drawn manually. The absolute activity in the ROIs was determined. RESULTS: Uptake values ranging from 0.71% to 21.87% of the injected activity were measured. A very strong linear correlation was found between the determined activity in vivo and ex vivo (r2=0.946; slope m=1.059). CONCLUSION: Quantification in vivo using this multi-pinhole SPECT system is highly accurate.

Animals↗
PubMed2005

[Schimke's immuno-osseous dysplasia as an explanation for the rare combination of disproportionately short stature and the nephrotic syndrome].

A 10-year-old Turkish boy with consanguineous parents was presented with a disproportionately short stature and a nephrotic syndrome. The mild form of Schimke's immuno-osseous dysplasia was diagnosed as the common cause. This rare, autosomal recessive osteochondrodysplasia is characterised by spondyloepiphyseal dysplasia, facial dysmorphism, T-cell immunodeficiency and progressive renal failure due to focal segmental glomerulosclerosis. In Schimke's immuno-osseous dysplasia, a severe early-onset form and a milder later-onset form can be distinguished on the basis of the clinical course. The patient was treated by fluid and salt restriction, enalapril and later also losartan, which led to a decrease in the proteinuria and an increase in serum albumin concentration. Two years later, the renal function was still normal.

Body Height↗
PubMed2005

Phase I study of concomitant chemoradiation with raltitrexed in locally advanced head and neck cancer.

In patients with non-resectable head and neck cancer concomitant chemoradiotherapy is increasingly used, especially in cases of oropharyngeal and hypopharyngeal tumours. Most chemoradiotherapy regimes contain cisplatin as a single agent or in combination with fluorouracil. However, not all patients are fit enough for a cisplatin-containing regime or they refuse hospital admission. Raltitrexed is a specific thymidylate synthase inhibitor that has been studied as a radiosensitiser in rectal cancer. Raltitrexed can be administered easily in an outpatient setting and has few short-term effects. We studied raltitrexed at escalating doses combined with standard radiotherapy in advanced head and neck cancer patients. Seventeen patients with locally advanced head and neck cancers were enrolled in the study. Raltitrexed was administered at dose levels of 1.5, 2.0, 2.5 and 3.0 mg/m(2) intravenously (i.v), once every 3 weeks, for two doses. Radiotherapy consisted of 70 Gy given over 7 weeks in five fractions of 2 Gy per week. In general, treatment toxicity (DLT), complicated febrile neutropenia, was observed at 3.0 mg/m(2) in two of four patients. The dose of 2.5 mg/m(2) was extended thereafter with additional patients without major toxicity. Radiotherapy had to be interrupted in one patient. Five patients had a clinical complete response(CR) and eleven a partial response (PR) six weeks after the last fraction of radiotherapy. Twelve out of 17 patients remained free of locoregional recurrence after a median follow-up of 24(+) months (range 3-60+ months). Raltitrexed, at a dose of 2.5 mg/m(2) given twice 3 weeks apart, can be administered in combination with 70 Gy of radiotherapy in locally advanced head and neck cancer patients with a manageable tolerability profile. The clinical results and convenience of the schedule make raltitrexed an attractive drug to explore further in patients considered unfit for cisplatin-containing chemoradiation regimens.

Aged↗
PubMed2005

Moraxella catarrhalis sepsis in a patient with juvenile spinal muscle atrophy.

Moraxella catarrhalis rarely causes severe infections or bacteraemia in healthy subjects. In the literature only four cases of clinical sepsis with M. catarrhalis have been described, mostly in immunocompromised patients. We describe a case of a 34-year-old patient with Kugelberg-Welander disease and low body weight (28 kg) who developed clinical sepsis due to M. catarrhalis bacteraemia. A review of the literature is given.

Adult↗
PubMed2004

The role of electromyography in clinical diagnosis of neuromuscular locomotor problems in the horse.

REASONS FOR PERFORMING STUDY: Systematically performed EMG needle examination of muscles provides essential information about the functional aspects of the motor unit. However, clinical studies in which information is given on the diagnostic and discriminative values of electromyography (EMG) in the horse are scarce. OBJECTIVES: To determine to what extent inclusion of EMG analysis in clinical examination contributes to determination of type and localisation of abnormality. METHODS: EMG analysis, complete clinical examination and diagnosis of 108 horses (mean +/- s.d. age 75 +/- 3.8 years; bodyweight 548 +/- 86 kg; height 1.67 +/- 0.07 m) were performed, and results without and with EMG analysis compared. RESULTS: Without EMG, myopathy and neuropathy were diagnosed in 20 and 58 horses, respectively, and with EMG in 17 and 82 horses. EMG changed localisation in myopathy and neuropathy in 12 and 37% of cases, respectively. Lesions in the C1-T2, T2-L3 and L3-S3 segments were, respectively, diagnosed without EMG in 7, 11 and 30%, and with EMG in 27, 7 and 17% of cases. Where no clinical diagnosis could be made prior to EMG, many patients appeared to be suffering from localised cervical lesions (29%) or generalised neuropathy (54%). CONCLUSIONS AND POTENTIAL RELEVANCE: The assistance of EMG in discriminating between normal, neuropathy and myopathy, and in locating pathology, contributes to diagnosis of neuromuscular problems.

Animals↗
PubMed2003

Stabilised 111In-labelled DTPA- and DOTA-conjugated neurotensin analogues for imaging and therapy of exocrine pancreatic cancer.

Neurotensin (NT) receptors are overexpressed in exocrine pancreatic cancer and Ewing's sarcoma. The potential utility of native NT in cancer diagnosis and therapy is, however, limited by its rapid degradation in vivo. Therefore, NT analogues were synthesised with modified lysine and arginine derivatives to enhance stability and coupled either to DTPA, to enable high specific activity labelling with indium-111 for imaging, or to DOTA, to enable high specific activity labelling with beta-emitting radionuclides, such as lutetium-177 and yttrium-90. Based on serum stability (4 h incubation at 37 degrees C in human serum) and receptor binding affinity, the five most promising analogues were selected and further evaluated in in vitro internalisation studies in human colorectal adenocarcinoma HT29 cells, which overexpress NT receptors. All five NT analogues bound with high affinity to NT receptors on human exocrine pancreatic tumour sections. The analogues could be labelled with (111)In to a high specific activity. The (111)In-labelled compounds were found to be very stable in serum. Incubation of HT29 cells with the (111)In-labelled analogues at 37 degrees C showed rapid receptor-mediated uptake and internalisation. The most promising analogue, peptide 2530 [DTPA-(Pip)Gly-Pro-(PipAm)Gly-Arg-Pro-Tyr-tBuGly-Leu-OH] was further tested in vivo in a biodistribution study using HT29 tumour-bearing nude mice. The results of this study showed low percentages of injected dose per gram tissue of this (111)In-labelled 2530 analogue in receptor-negative organs like blood, spleen, pancreas, liver, muscle and femur. Good uptake was found in the receptor-positive HT29 tumour and high uptake was present in the kidneys. Co-injection of excess unlabelled NT significantly reduced tumour uptake, showing that tumour uptake is a receptor-mediated process. With their enhanced stability, maintained high receptor affinity and rapid receptor-mediated internalisation, the (111)In-labelled DTPA- and DOTA-conjugated NT analogues are excellent candidates for imaging and therapy of exocrine pancreatic cancer, peptide 2530 being the most promising analogue.

Animals↗
PubMed2003

Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate.

Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [(90)Y-DOTA(0),Tyr(3)]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA(0),Tyr(3)]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA(0),Tyr(3)]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide (177)Lu, it has proved very successful in achieving tumour regression in animal models. The effects of (177)Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi (177)Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours. However, in view of the high success rate of therapy with (177)Lu-octreotate and the absence of serious side-effects, we advocate its use in patients with GEP tumours without waiting for tumour progression.

Abdominal Pain↗
PubMed2002

The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity.

Peptide receptor-targeted radionuclide therapy is nowadays also being performed with DOTA-conjugated peptides, such as [DOTA(0),Tyr(3)]octreotate, labelled with radionuclides like (177)Lu. The incorporation of (177)Lu is typically >/=99.5%; however, since a total patient dose can be as high as 800 mCi, the amount of free (177)Lu(3+) (= non-DOTA-incorporated) can be substantial. Free (177)Lu(3+) accumulates in bone with unwanted irradiation of bone marrow as a consequence. (177)Lu-DTPA is reported to be stable in serum in vitro, and in vivo it has rapid renal excretion. Transforming free Lu(3+) to Lu-DTPA might reroute this fraction from accumulation in bone to renal clearance. We therefore investigated: (a) the biodistribution in rats of (177)LuCl(3), [(177)Lu-DOTA(0),Tyr(3)]octreotate and (177)Lu-DTPA; (b) the possibilities of complexing the free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate to (177)Lu-DTPA prior to intravenous injection; and (c) the effects of free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate, in the presence and absence of DTPA, on the biodistribution in rats. (177)LuCl(3) had high skeletal uptake (i.e. 5% ID per gram femur, with localization mainly in the epiphyseal plates) and a 24-h total body retention of 80% injected dose (ID). [(177)Lu-DOTA(0),Tyr(3)]octreotate had high and specific uptake in somatostatin receptor-positive tissues, and 24-h total body retention of 19% ID. (177)Lu-DTPA had rapid renal clearance, and 24-h total body retention of 4% ID. Free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate could be complexed to (177)Lu-DTPA. Accumulation of (177)Lu in femur, blood, liver and spleen showed a dose relation to the amount of free (177)Lu(3+), while these accumulations could be normalized by the addition of DTPA. After labelling [DOTA(0),Tyr(3)]octreotate with (177)Lu the addition of DTPA prior to intravenous administration of [(177)Lu-DOTA(0),Tyr(3)]octreotate is strongly recommended.

Animals↗
PubMed2001

[177Lu-DOTA(0),Tyr3] octreotate for somatostatin receptor-targeted radionuclide therapy.

Receptor-targeted scintigraphy using radiolabeled somatostatin analogs such as octreotate is being used with great success to demonstrate the in vivo presence of somatostatin receptors on various tumors. A new and promising application for these analogs is radionuclide therapy. Radionuclides suitable for this application include the Auger electron-emitter (111)In and the beta-emitters (90)Y (high energy) and (177)Lu (low energy). We investigated [DOTA(0),Tyr(3)]octreotate, labeled with the lanthanide (177)Lu, in biodistribution and radionuclide therapy experiments using male Lewis rats bearing the somatostatin receptor-positive rat CA20948 pancreatic tumor. Biodistribution studies in Lewis rats showed the highest uptake in the rat pancreatic CA20948 tumor and sst(2)-positive organs, which include the adrenals, pituitary and pancreas, of [(177)Lu-DOTA(0),Tyr(3)]octreotate in comparison with (88)Y- and (111)In-labeled analogs. Kidney uptake of [(177)Lu-DOTA(0),Tyr(3)]octreotate could be reduced by approximately 40% by co-injection of 400 mg/kg D-lysine. In radionuclide therapy studies, a 100% cure rate was achieved in the groups of rats bearing small (< or =1 cm(2)) CA20948 tumors after 2 doses of 277.5 MBq or after a single dose of 555 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate. A cure rate of 75% was achieved after a single administration of 277.5 MBq. In rats bearing larger (> or =1 cm(2)) tumors, 40% and 50% cure rates were achieved in the groups that received 1 or 2 277.5 MBq injections of [(177)Lu-DOTA(0),Tyr(3)]octreotate, respectively. After therapy with [(177)Lu-DOTA(0),Tyr(3)]octreotide in rats bearing small tumors, these data were 40% cure after 1 injection with 277.5 MBq and 60% cure after 2 repeated injections. In conclusion, [(177)Lu-DOTA(0),Tyr(3)]octreotate has demonstrated excellent results in radionuclide therapy studies in rats, especially in animals bearing smaller tumors. This candidate molecule shows great promise for radionuclide therapy in patients with sst(2)-expressing tumors.

Animals↗
PubMed2001

Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives.

In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, "new" radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy.

Humans↗
PubMed2001

[177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients.

The somatostatin analogue [DOTA0,Tyr3]octreotate has a nine-fold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA0, Tyr3]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide lutetium-177, this compound has been shown to have a very favourable impact on tumour regression and animal survival in a rat model. Because of these reported advantages over the analogues currently used for somatostatin receptor-mediated radiotherapy, we decided to compare [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) with [111In-DTPA0]octreotide (111In-octreotide) in six patients with somatostatin receptor-positive tumours. Plasma radioactivity after 177Lu-octreotate expressed as a percentage of the injected dose was comparable with that after 111In-octreotide. Urinary excretion of radioactivity was significantly lower than after 111In-octreotide, averaging 64% after 24 h. The uptake after 24 h, expressed as a percentage of the injected dose of 177Lu-octreotate, was comparable to that after 111In-octreotide for kidneys, spleen and liver, but was three- to fourfold higher for four of five tumours. The spleen and kidneys received the highest absorbed doses. The doses to the kidneys were reduced by a mean of 47% after co-infusion of amino acids. It is concluded that in comparison with the radionuclide-coupled somatostatin analogues that are currently available for somatostatin receptor-mediated radiotherapy, 177Lu-octreotate potentially represents an important improvement. Higher absorbed doses can be achieved to most tumours, with about equal doses to potentially dose-limiting organs; furthermore, the lower tissue penetration range of 177Lu as compared with 90Y may be especially important for small tumours.

Adolescent↗
PubMed2001

Somatostatin receptor imaging, therapy and new strategies in patients with neuroendocrine tumours.

BACKGROUND: Somatostatin receptors have been found on a variety of neuroendocrine tumours, such as carcinoids and paragangliomas, as well as on most pancreatic endocrine and breast tumours. Somatostatin receptor scintigraphy with a radionuclide-labelled somatostatin analogue, [111Indium- diethylenetriaminopenta-acetic acid]octreotide, is a sensitive and specific technique for visualizing in vivo the presence of somatostatin receptors on various tumours. METHODS: Material was identified from previous review articles, references cited in original papers and a Medline search of the literature. Additional material was obtained from recently published abstracts of meetings. RESULTS AND CONCLUSION: Somatostatin receptor imaging of neuroendocrine tumours is essential in the diagnostic evaluation of most of these tumours. The expression of somatostatin receptors in vivo not only predicts the outcome of somatostatin analogue treatment but also opens the possibility of new therapeutic strategies. Because better information about spread of the disease can be obtained, more justifiable options for therapy can be proposed.

Genetic Therapy↗
PubMed2001

Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability.

Although it was originally believed that thyroid hormones enter target cells by passive diffusion, it is now clear that cellular uptake is effected by carrier-mediated processes. Two stereospecific binding sites for each T4 and T3 have been detected in cell membranes and on intact cells from humans and other species. The apparent Michaelis-Menten values of the high-affinity, low-capacity binding sites for T4 and T3 are in the nanomolar range, whereas the apparent Michaelis- Menten values of the low-affinity, high-capacity binding sites are usually in the lower micromolar range. Cellular uptake of T4 and T3 by the high-affinity sites is energy, temperature, and often Na+ dependent and represents the translocation of thyroid hormone over the plasma membrane. Uptake by the low-affinity sites is not dependent on energy, temperature, and Na+ and represents binding of thyroid hormone to proteins associated with the plasma membrane. In rat erythrocytes and hepatocytes, T3 plasma membrane carriers have been tentatively identified as proteins with apparent molecular masses of 52 and 55 kDa. In different cells, such as rat erythrocytes, pituitary cells, astrocytes, and mouse neuroblastoma cells, uptake of T4 and T3 appears to be mediated largely by system L or T amino acid transporters. Efflux of T3 from different cell types is saturable, but saturable efflux of T4 has not yet been demonstrated. Saturable uptake of T4 and T3 in the brain occurs both via the blood-brain barrier and the choroid plexus-cerebrospinal fluid barrier. Thyroid hormone uptake in the intact rat and human liver is ATP dependent and rate limiting for subsequent iodothyronine metabolism. In starvation and nonthyroidal illness in man, T4 uptake in the liver is decreased, resulting in lowered plasma T3 production. Inhibition of liver T4 uptake in these conditions is explained by liver ATP depletion and increased concentrations of circulating inhibitors, such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, indoxyl sulfate, nonesterified fatty acids, and bilirubin. Recently, several organic anion transporters and L type amino acid transporters have been shown to facilitate plasma membrane transport of thyroid hormone. Future research should be directed to elucidate which of these and possible other transporters are of physiological significance, and how they are regulated at the molecular level.

Animals↗
PubMed2001

Tumor response after [(90)Y-DOTA(0),Tyr(3)]octreotide radionuclide therapy in a transplantable rat tumor model is dependent on tumor size.

UNLABELLED: A promising application of radiolabeled somatostatin analogs is peptide receptor-targeted radionuclide therapy of somatostatin receptor-expressing tumors. A suitable radionuclide is (90)Y, which emits high-energy beta-particles with a pathlength of several millimeters in tissue, making it especially promising for treatment of large tumors. METHODS: We investigated the radiotherapeutic effect of different activities (111 and 370 MBq) of [(90)Y-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)(0),Tyr(3)]octreotide in Lewis rats bearing somatostatin receptor-positive rat pancreatic CA20948 tumors of different size (0.08-15 cm(2)) in their flank. RESULTS: Dose-dependent radiotherapeutic effects of (90)Y-labeled octreotide in this rat tumor model were found. Tumor control (100% complete response) was found in animals bearing tumors of 3-9 cm(2) (mean, 7.8 cm(2)) after intravenous injection of the highest activity (370 MBq [(90)Y-DOTA(0),Tyr(3)]octreotide). In rats bearing tumors of < or =1 cm(2) or > or =14 cm(2), the effects were less pronounced (50% and 0% complete response, respectively). In tumors of < or =1 cm(2) the (90)Y radiation energy will not be absorbed completely in the tumor, whereas in tumors of > or =14 cm(2) the increased number of clonogenic and probably hypoxic tumor cells may explain the failure to reach a cure. CONCLUSION: This study shows the ability of [(90)Y-DOTA(0),Tyr(3)]octreotide to control tumor growth, especially in medium-sized tumors. The effect of radionuclide therapy appeared to be dependent on tumor size at the onset of therapy.

Animals↗
PubMed2000

Evaluation of a radiolabelled cyclic DTPA-RGD analogue for tumour imaging and radionuclide therapy.

Tumours depend on sufficient blood supply for their growth. They are able to promote new blood vessel formation (neoangiogenesis) via angiogenic factors. Inhibition of this process results in tumour involution or necrosis. RGD (Arg-Gly-Asp) peptides are described to antagonise neoangiogenesis, e.g., by binding to alpha(v)beta(3) receptors on blood vessels. In order to visualise neoangiogenesis in tumours in vitro and in vivo, we introduced and tested an RGD analogue [c(Arg-Gly-Asp-D-Tyr-Lys)], coupled to the chelator diethyleletriamepentaacetic acid (DTPA). This analogue can be radiolabelled with both (111)In and (125)I. In autoradiography and immunohistochemistry studies, the (125)I-labelled analogue appeared to bind specifically and with high affinity to alpha(v)beta(3) receptors on neovascular blood vessel sections of different major human cancers, like prostate and breast cancer, which express these receptors. This radioiodinated radiopharmaceutical also bound to and internalised in human carcinoid Bon cells and rat pancreatic CA20948 tumour cells. Internalisation was receptor-specific and appeared to be time and temperature dependent. In vivo in rats, we investigated administration of different peptide amounts (0.1, 0.5, and 100 microg). The best amount of the radiolabelled analogue to be administered to rats appeared to be 0.1 microg/rat, as uptake decreased with increasing peptide amount. We also found receptor-specific accumulation of the (111)In-labelled analogue in the transplantable pancreatic tumour CA20948. The introduction of the DTPA group in this peptide resulted in renal clearance of the radiopharmaceutical, in contrast to the non-DTPA-conjugated compound that is cleared predominantly via the liver. (111)In emits Auger and conversion electrons besides gamma radiation, therefore, this radiopharmaceutical is suitable not only for tumour scintigraphy but also has potential for radionuclide therapy of major human cancers as well. Moreover, after coupling to the chelator DOTA, the analogue could be radiolabelled in a stable way with beta-emitters, e.g., (90)Y and (177)Lu, enlarging its potential. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 186-198 (2000).

Animals↗
PubMed2000

The role of radioactive somatostatin and its analogues in the control of tumor growth.

Peptide receptor scintigraphy with the radioactive somatostatin analogue [111In-DTPA-D-Phe1]octreotide is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumors. With this technique primary tumors and metastases of neuroendocrine cancers as well as of many other cancer types can be localized. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy with repeated administration of high doses of [111In-DTPA-D-Phe1]octreotide. 111In emits Auger and conversion electrons, having a tissue penetration of 0.02-10 microns and 200-500 microns, respectively. Thirty end-stage patients with mostly neuroendocrine progressing tumors were treated with [111In-DTPA-D-Phe1]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase-I trial. There were no major clinical side effects after up to 2 years of treatment, except that in a few patients a transient decline in platelet counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production, and tumor proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight showed stabilization of disease and six others a reduction in tumor size. There is a tendency towards better results in patients whose tumors have a higher accumulation of the radioligand. Peptide receptor radionuclide therapy is also feasible with 111In as the radionuclide. Theoretically, depending on the homogeneity of distribution of tumor cells expressing peptide receptors and the size of the tumor, beta-emitting radionuclides, e.g., 90Y, labeled to DOTA-chelated peptides may be more effective than 111In for peptide receptor radionuclide therapy. The first peptide receptor radionuclide therapy trials with [90Y-DOTA-Tyr3]octreotide started recently.

Cell Division↗