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P P van Rijk

Publications and source records attributed to P P van Rijk.

At least 19 recordsLinked to original sources
PubMed2006

Production of GMP-grade radioactive holmium loaded poly(L-lactic acid) microspheres for clinical application.

Radioactive holmium-166 loaded poly(L-lactic acid) microspheres are promising systems for the treatment of liver malignancies. The microspheres are loaded with holmium acetylacetonate (HoAcAc) and prepared by a solvent evaporation method. After preparation, the microspheres (Ho-PLLA-MS) are activated by neutron irradiation in a nuclear reactor. In this paper, the aspects of the production of a (relatively) large-scale GMP batch (4 g, suitable for treatment of 5-10 patients) of Ho-PLLA-MS are described. The critical steps of the Ho-PLLA-MS production process (sieving procedure, temperature control during evaporation and raw materials) were considered and the pharmaceutical quality of the microspheres was evaluated. The pharmaceutical characteristics (residual solvents, possible bacterial contaminations and endotoxins) of the produced Ho-PLLA-MS batches were in compliance with the requirements of the European Pharmacopoeia. Moreover, neutron irradiated Ho-PLLA-MS retained their morphological integrity and the holmium remained stably associated with the microspheres; it was observed that after 270h (10 times the half-life of Ho-166) only 0.3+/-0.1% of the loading was released from the microspheres in an aqueous solution. In conclusion, Ho-PLLA-MS which are produced as described in this paper, can be clinically applied, with respect to their pharmaceutical quality.

Brachytherapy↗
PubMed2005

Lanthanide bearing microparticulate systems for multi-modality imaging and targeted therapy of cancer.

The rapid developments of high-resolution imaging techniques are offering unique possibilities for the guidance and follow up of recently developed sophisticated anticancer therapies. Advanced biodegradable drug delivery systems, e.g. based on liposomes and polymeric nanoparticles or microparticles, are very effective tools to carry these anticancer agents to their site of action. Elements from the group of lanthanides have very interesting physical characteristics for imaging applications and are the ideal candidates to be co-loaded either in their non-radioactive or radioactive form into these advanced drug delivery systems because of the following reasons: Firstly, they can be used both as magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and for single photon emission computed tomography (SPECT). Secondly, they can be used for radionuclide therapies which, importantly, can be monitored with SPECT, CT, and MRI. Thirdly, they have a relatively low toxicity, especially when they are complexed to ligands. This review gives a survey of the currently developed lanthanide-loaded microparticulate systems that are under investigation for cancer imaging and/or cancer therapy.

Animals↗
PubMed2002

Simultaneous (99m)Tc/(201)Tl dual-isotope SPET with Monte Carlo-based down-scatter correction.

In simultaneous technetium-99m/thallium-201 dual-isotope (DI) single-photon emission tomography (SPET), down-scatter of (99m)Tc photons contaminates the (201)Tl image, which leads to a decrease in lesion contrast and loss of quantitative accuracy. Correction for down-scatter can be achieved by first reconstructing the (99m)Tc activity distribution. Subsequently, the (99m)Tc down-scatter in the (201)Tl photopeak window is simulated and used for correction during iterative reconstruction of the (201)Tl image. In this work, the down-scatter projections are calculated using a dedicated Monte Carlo simulator which is able to efficiently model the detection of lead X-rays from the collimator. An anthropomorphic torso phantom with a cardiac insert with and without cold lesions was used for evaluation of the proposed method. Excellent agreement in lesion contrast and quantitative accuracy was found between the down-scatter corrected DI-SPET (201)Tl image and the virgin (i.e. separately acquired) (201)Tl image, in particular when the effects of lead X-rays were included. Compensation for the noise added by down-scatter to the (201)Tl image can be achieved by using a 15% lower dose of (99m)Tc, a 15% increase in scan time and a 12% increase in (201)Tl dose. In conclusion, the Monte Carlo-based down-scatter correction recovers lesion contrast and quantitative accuracy in DI-SPET (201)Tl images almost perfectly. In addition, degradations due to the added noise of down-scatter in simultaneous DI-SPET can be prevented by slight adaptations to the data acquisition protocol.

Humans↗
PubMed2002

Influence of neutron irradiation on holmium acetylacetonate loaded poly(L-lactic acid) microspheres.

Holmium-loaded microspheres are useful systems in radio-embolization therapy of liver metastases. For administration to a patient, the holmium-loaded microspheres have to be irradiated in a nuclear reactor to become radioactive. In this paper. the influence of neutron irradiation on poly(L-lactic acid) (PLLA) microspheres and films, with or without holmium acetylacetonate (HoAcAc), is investigated, in particular using differential scanning calorimetry (MDSC), scanning electron microscopy, gel permeation chromatography (GPC), infrared spectroscopy, and X-ray diffraction. After irradiation of the microspheres, only minor surface changes were seen using scanning electron microscopy, and the holmium complex remained immobilized in the polymer matrix as reflected by a relatively small release of this complex. GPC and MDSC measurements showed a decrease in molecular weight and crystallinity of the PLLA, respectively, which can be ascribed to radiation induced chain scission. Irradiation of the HoAcAc loaded PLLA matrices resulted in evaporation of the non-coordinated and one coordinated water molecule of the HoAcAc complex, as evidenced by MDSC and X-ray diffraction analysis. Infrared spectroscopy indicated that some degradation of the acetylacetonate anion occurred after irradiation. Although some radiation induced damage of both the PLLA matrix and the embedded HoAcAc-complex occurs, the microspheres retain their favourable properties (no marginal release of Ho, preservation of the microsphere size), which make these systems interesting candidates for the treatment of tumours by radio-embolization.

Calorimetry, Differential Scanning↗
PubMed2002

Advances in nuclear oncology: microspheres for internal radionuclide therapy of liver tumours.

Liver metastases cause the majority of deaths from colorectal cancer, and response to chemotherapy and external radiotherapy is poor. An alternative is internal radionuclide therapy using (90)Y labeled microspheres. These microspheres are very stable and have a proven efficacy in the field of treatment of primary or metastatic hepatic cancer. Whilst these glass spheres showed encouraging results in patients, their high density is a serious drawback. Currently, other materials with lower densities and other radioisotopes are being investigated in order to optimize this promising new therapy. Three major radiolabeled microsphere materials, viz. glass, resin-based and polymer-based, are now available for therapy or are being tested in animals. In this review the preparation, stability and degradation of these spheres are discussed.

Animals↗
PubMed2001

F-18-fluoro-deoxy-glucose positron-emission tomography scanning in detection of local recurrence after radiotherapy for laryngeal/ pharyngeal cancer.

BACKGROUND: The objective of this investigation was to determine whether F18-fluoro-deoxy-glucose (FDG) positron-emission tomography (PET) could differentiate between local recurrence and late radiation effects after radiotherapy for laryngeal/pharyngeal cancer. METHODS: In a prospective study of 75 patients (67 larynx, eight oro/hypopharynx), 160 laryngoscopies and 109 FDG PET scans were performed on the head and neck region. The mean follow-up time after the first FDG PET scan was 23 months (minimum 1 year). RESULTS: Local recurrence was diagnosed in 37 patients: 19 after the first biopsy and 18 after follow-up biopsies. For all of the negative initial FDG scans (27), the biopsies that were taken at the same time were negative and no recurrence was seen for at least 1 year. The first FDG scan was a true positive in 34 of 48 patients. In 12 of the 14 patients with false-positive results, FDG scans were repeated; a decreased FDG uptake was found in 9 of the 12. The sensitivity and specificity of the first scan were respectively 92% and 63%; including subsequent FDG scans, the rates were 97% and 82%, respectively. CONCLUSIONS: When a local recurrence is suspected after radiotherapy for cancer of the larynx/pharynx, an FDG PET scan should be the first diagnostic step. No biopsy is needed if the scan is negative. If the scan is positive and the biopsy negative, a decreased FDG uptake measured in a follow-up scan indicates that a local recurrence is unlikely.

Adult↗
PubMed2001

Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin.

Serum thyroglobulin (Tg) is usually the best marker of residual or metastatic disease after treatment of differentiated thyroid cancer. We evaluated the effect of so-called blind therapeutic doses of iodine-131 in patients with detectable Tg during suppressive levothyroxine treatment (Tg-on), and in patients with a negative diagnostic scintigram but detectable Tg during the hypothyroid phase (Tg-off). Twenty-two patients with differentiated thyroid carcinoma underwent total thyroidectomy and radioiodine ablation. During the follow-up, six patients with detectable Tg-on and 16 patients with detectable Tg-off were identified. All patients were treated with a blind therapeutic dose of 7,400 MBq iodine-131. Diagnostic scintigrams were compared with post-treatment scintigrams. Tg-off was measured in 16 cases, 1 year after the administration of the blind therapeutic dose, at the time of the follow-up diagnostic scintigram. Six patients were followed up by Tg-on only. Post-therapy scintigrams revealed previously undiagnosed local recurrence or distant metastases in 13/22 cases (59%); the remaining nine post-therapy scintigrams were negative. At the time of the blind therapeutic doses, Tg-off values ranged from 8 to 608 microg/l. After 1 year of follow-up, Tg-off decreased in 14/16 (88%) patients. In all patients who were followed by Tg-on only (n=6), a decrease in Tg values was measured. It is concluded that blind therapeutic doses resulted in a decrease in Tg levels in the majority of patients with suspected recurrence or metastases. The post-treatment scintigrams revealed pathological uptake in 59% of patients.

Adult↗
PubMed2001

Quantitative baseline renography 48 hours after renal transplantation predicts long-term graft survival.

Technetium-99m mercaptoacetylglycine (99mTc-MAG3) renography is a successful non-invasive method for the evaluation of renal transplants. In this study we prospectively studied 256 patients after renal transplantation, using the MAG3 uptake capacity in the first 10 min (MUC10), which is an index of renal function representing kidney activity as a fraction of the injected dose. Renal scintigraphy was performed in all patients within 48 h of transplantation. Renograms were obtained over 20 min, after bolus injection of +/-100 MBq 99mTc-MAG3. MUC10 ranged between 0.0 and 94.9. The patients were divided into five groups: group 1, MUC10 <1; group 2, 1< or =MUC10 < 5; group 3, 5 < or = MUC10 <10; group 4, 10 < or = MUC10 < 30; group 5, MUC10 > or =30. In 235 patients, follow-up for 5 years was completed. Considering all the renal transplants, 30% of the grafts ceased functioning within the first 5 years. Six grafts showed a MUC10 of < 1, and none survived the first year. After 5 years, 43% of the grafts with a MUC10 of 1-5 still functioned, as compared with 63% of those with a MUC10 of 5-10, 72% of those with a MUC10 of 10-30 and 83% of those with a MUC10 of > or =30. Kaplan-Meier survival analysis showed significant differences between the five different patient groups based on MUC10 in terms of the percentage of kidneys that ceased to function within 5 years. The period of cold ischaemia and the donor age were known in 178 patients. In contrast to cold ischaemia time, the MUC10 and the donor age showed a significant effect (P<0.05) on graft survival. This study indicates that the MUC10 early after renal transplantation is useful as a prognostic factor in the evaluation of kidney transplants and that a MUC10 of <1 indicates a dismal prognosis for the renal transplant.

Adult↗
PubMed2001

Characterization of poly(L-lactic acid) microspheres loaded with holmium acetylacetonate.

Holmium-loaded PLLA microspheres are useful systems in radioembolization therapy of liver metastases because of their low density, biodegradability and favourable radiation characteristics. Neutron activated Ho-loaded microspheres showed a surprisingly low release of the relatively small holmium complex. In this paper factors responsible for this behaviour are investigated, in particular by the use of differential scanning calorimetry, scanning electron microscopy, infrared spectroscopy and X-ray diffraction. The holmium complex is soluble in PLLA up to 8% in films and 17% in microspheres. Interactions between carbonyl groups of PLLA, and the Ho-ion in the HoAcAc complex, explain very satisfactorily the high stability of holmium-loaded microspheres.

Biocompatible Materials↗
PubMed2001

Impact of delayed gastric emptying on the outcome of antireflux surgery.

OBJECTIVE: To study the effect of Nissen fundoplication on the pattern of gastric emptying and intragastric distribution of symptoms in patients with normal and delayed gastric emptying before surgery, especially in those with delayed emptying before surgery. SUMMARY BACKGROUND DATA: Gastroesophageal reflux disease is associated with delayed gastric emptying and dyspeptic symptoms in approximately 40% of the patients. After Nissen fundoplication, dyspeptic symptoms are also not uncommon. METHODS: Thirty-six patients (26 men, 10 women, mean age 43.1) were studied before and 3 months after Nissen fundoplication. Gastric emptying (dual-isotope, expressed in lag phase, emptying rate, T50, and intragastric distribution) was not included in the decision for surgery. Reflux-related and dyspeptic symptoms were scored before and at 3, 6, and 12 months after surgery. RESULTS: Twenty-six patients had normal and 10 had delayed gastric emptying before surgery. Nissen fundoplication on average enhanced gastric emptying for solids in both subgroups by a combination of a decrease in mean lag phase, emptying rate, and T50. The preoperative difference in intragastric distribution between patients with and without delayed gastric emptying was abolished by fundoplication. Patients with normal gastric emptying before surgery showed an increase in early postprandial satiety; in those with delayed emptying, this was not observed. A correlation was found between preoperative T50 for liquid gastric emptying and postoperative nausea at 3 months in patients with normal gastric emptying. In patients with delayed emptying, preoperative correlations between lag phase for liquids and nausea respectively early satiety were significant, as well as for T50 for liquids and vomiting. CONCLUSIONS: Nissen fundoplication equalizes the preoperative difference in intragastric distribution and accelerates gastric emptying without an effect on symptoms in patients with preexisting delayed gastric emptying, but with an increase in early satiety in patients with normal gastric emptying. Delayed gastric emptying is not a contraindication for antireflux surgery.

Adult↗
PubMed2001

Captopril renography and the relevance of abnormal but bilateral identical curves in the diagnosis of renal artery stenosis.

BACKGROUND: Captopril renography (CR) has been shown to improve the effectiveness of renal scintigraphy in renovascular hypertension, by inhibiting angiotensin-converting enzyme. CR is particularly sensitive and specific in unilateral renal artery stenosis (RAS), but results in patients with bilateral RAS are less favourable. The aim of this study was to investigate the meaning of abnormal but identical renographic curves in the diagnosis of RAS. PATIENTS AND METHODS: One hundred and fifty-eight patients clinically suspected for renovascular hypertension underwent CR, using 50 MBq (99)Tc(m)-mercaptoacetyltriglycine ((99)Tc(m)-MAG(3)), prior to performing renal angiography. CR was performed 1 h after captopril administration. Renograms were analysed according to the consensus criteria. All patients underwent angiography, considered as the "gold standard" in the detection of the presence of RAS (stenosis >50% was defined as significant). All kidneys were categorized into three groups, scintigraphically as well as angiographically: no stenosis, unilateral stenosis and bilateral stenosis. RESULTS: Out of 158 patients 100 (63%) showed a RAS on angiography (58 (37%) unilateral, 42 (26%) bilateral). The sensitivity and specificity of CR evaluated by patient was 83% and 75%, respectively. Thirty patients with completely identical curves were identified, 21 patients with normal curves and nine patients with abnormal identical curves. All but one patient showed no RAS on the angiogram. In this single patient a unilateral stenosis was found. CONCLUSION: Identical curves on the renogram generally suggest no RAS and are probably due to intrinsic parenchymal disease.

Adult↗
PubMed2000

Preoperative evaluation of patients with primary head and neck cancer using dual-head 18fluorodeoxyglucose positron emission tomography.

OBJECTIVE: To evaluate the value of 18fluorodeoxyglucose (FDG) positron emission tomography (PET) in primary head and neck cancer. BACKGROUND DATA: Head and neck carcinomas tend to metastasize to regional lymph nodes rather than to spread hematogenously. With nodal metastases, cure rates decrease by approximately 50%. Moreover, in approximately 3% of the patients, a second primary tumor is found at initial presentation. METHODS: Fifty-four consecutive patients (31 men and 23 women; mean age 60 years, range 34-81 years) with previously untreated squamous cell carcinomas of the oral cavity or oropharynx were studied. Before surgery and within a period of 3 weeks, clinical examination, chest x-ray, computed tomography (CT), ultrasonography with fine-needle aspiration cytology (US/ FNAC), and FDG-PET were performed. All study results were scored per neck side and were also classified as 0 (no metastases), 1 (single metastasis), or 2 (multiple metastases). RESULTS: The sensitivity for the detection of lymph node metastases per neck side was 96%, 85%, and 64% for FDG-PET, CT, and US/FNAC, respectively. The specificity was 90%, 86%, and 100% for FDG-PET, CT, and US/FNAC, respectively. In terms of the classification, FDG-PET showed the best correlation with the histologic data. Finally, in nine patients (17%), a second primary tumor was detected by FDG-PET and confirmed by histologic evaluation. CONCLUSION: Because of the high prevalence of second primary tumors detected by FDG-PET and the decreased error rate in the assessment of lymph node involvement compared with CT and US, FDG-PET should be routinely performed in patients with primary head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed2000

Minimizing liver, bowel, and gastric activity in myocardial perfusion SPECT.

UNLABELLED: When using 99mTc-tetrofosmin for myocardial perfusion SPECT, increased liver, intestinal, or gastric activity may create a major problem in the visual and quantitative interpretation Of the inferoposteroseptal walls, particularly at rest. The aim of this study was to determine what measures were required to minimize this extracardial activity. METHODS: Ninety-seven patients had a SPECT scan at rest without attenuation correction. They were divided into 3 groups. Preparation consisted of no action taken (group 1), 150 mL whole milk 10 min after administration of tetrofosmin (group 2), or 450 mL water 10 min before acquisition (group 3). A further 55 patients had a SPECT scan at rest with attenuation correction. They were also divided into 3 groups, and preparation consisted of 150 mL whole milk 10 min after administration of tetrofosmin (group 4), 450 mL water 10 min before acquisition (group 5), or both whole milk and water (group 6). The presence of activity in liver, bowel, and stomach was determined visually on reconstructed images. Activity was defined as interfering when it might result in either an underestimation or an overestimation of the uptake in the myocardial wall. RESULTS: Interfering activity was seen in 83% of the patients in group 1, in 74% in group 2, in 33% in group 3, in 61% in group 4, in 67% in group 5, and in 20% of group 6. CONCLUSION: The interpretation of inferoposteroseptal wall activity on myocardial rest SPECT images is facilitated by having the patient drink both whole milk and water at specified times before data acquisition.

Adult↗
PubMed1999

18F-fluorodeoxyglucose dual-head positron emission tomography as a procedure for detecting simultaneous primary tumors in cases of head and neck cancer.

BACKGROUND: Second primary tumors are a leading cause of death among patients with head and neck cancer; therefore, early detection of these tumors is necessary. In the current study, the authors aimed to evaluate the diagnostic capacity of (18)F-fluorodeoxyglucose dual-head positron emission tomography (FDG-PET) for detecting second primary tumors in patients presenting with primary head and neck cancer. METHODS: The authors prospectively studied a case series of 68 consecutive patients with a primary tumor in the oral cavity or oropharynx. Within a period of 3 weeks, clinical examination, chest X-ray, computed tomography, and ultrasonography of the head and neck were performed on all patients. Irrespective of the results, patients underwent FDG-PET of the head, neck, and chest. Due to its low yield in the detection of second primary tumors, panendoscopy was not used in this study. All patients were followed up for at least 6 months to assess the number of simultaneous and synchronous tumors missed by FDG-PET. RESULTS: In 12 of 68 patients (18%; 95% confidence interval [CI]: 8-28%), a second simultaneous primary malignant tumor was found by FDG-PET. Five of these tumors (7%; 95% CI: 1-13%) were also detected by clinical or radiologic examination (P = 0.016). With one exception, all tumors were found in the epithelium of the upper digestive and respiratory tract. However, even when the patient with a second primary tumor in the thyroid was excluded from evaluation, FDG-PET significantly improved the detection rate of second primaries (P = 0.031). In none of the 68 patients studied were additional simultaneous or synchronous primary tumors found during follow-up. CONCLUSIONS: The use of FDG-PET significantly increases the rate of detection of simultaneous second primary tumors. The results of our study suggest that most of the second primary tumors are detected in an early stage.

Adult↗
PubMed1999

Towards quality assurance of the sentinel node procedure in malignant melanoma patients: a single institution evaluation and a European survey.

The status of the regional lymph node (LN) is a critical component in staging patients with malignant melanoma. Biopsy of the first tumour-draining LN (sentinel node, SN) may replace routine elective LN dissection. However, until now, the applied methods have differed widely. Therefore, the aim of this study was to formulate recommendations for the pre-operative identification and intra-operative retrieval of the SN. We present the results of an independent survey of the clinical practice of the SN procedure via a postal questionnaire among 136 nuclear physicians in different institutes throughout 16 European countries. Moreover, the results of the SN procedure in our institution in an open prospective intervention trial in 80 patients with malignant melanoma without palpable LNs are also presented. In our protocol, on average, 6 h prior to surgery, 80 MBq technetium-99m nanocolloid was injected intracutaneously around the circumference of the diagnostic excision scar of the primary melanoma. No additional blue dye procedure was used to judge the accuracy of the radioguided SN procedure on its own. For successful identification of the radiolabelled SN, dynamic and static images were performed and the skin projection of the detected SN was marked with a cobalt-57 source. For intra-operative mapping a hand-held gamma probe was used. Forty of the 83 respondents of the European-wide questionnaire (48%) performed the SN procedure. Although many different regimens are used, the following recommendations could be deduced for the SN procedure in patients with malignant melanoma and non-palpable LNs: (1) local, intradermal injection of 40 MBq 99mTc-nanocolloid around the diagnostic excision scar of the primary melanoma; (2) two-phase LS: dynamic imaging (20 frames of 60 s, 128x128 matrix, LEAP collimator) followed by static images 1-2 h later (180 s per record); (3) intra-operative retrieval of the SN with a gamma probe; (4) histopathological examination of the SN on serial sections. In our trial, surgical retrieval of the SN was successful in 95% of the cases. Dynamic lymphoscintigraphy (LS) contributed to the SN procedure by showing anatomically unpredictable lymph flow to extra-regional SNs (10% of the patients in this study) and multiple SNs. Of the 77 retrieved SNs, 13 contained metastatic disease (17%). Consequently, these patients underwent a formal LN dissection of the affected basin. In conclusion, the SN concept is a rational approach to select patients who could, theoretically, benefit from early LN dissection of the affected basin. Standardisation of the SN procedure will improve the results of this approach, and could be useful for quality control and for making comparisons with other countries in coming years.

Adolescent↗
PubMed1999

Preoperative assessment of cervical lymph nodes in head and neck cancer with fluorine-18 fluorodeoxyglucose using a dual-head coincidence camera: a pilot study.

The aim of this study was to investigate whether in patients with head and neck cancer, staging is possible with fluorine-18 fluorodeoxyglucose (18F-FDG) using a dual-head positron emission tomography (PET) camera. Twenty patients (ten men, ten women; mean age: 60 years) were studied using 185 MBq (5 mCi) 18F-FDG. Two of these patients who were suspected of having recurrence in the neck were restaged 19 and 12 months, respectively, after the resection of the primary tumour. The images were visually analyzed and the results were correlated with computed tomography (CT) (n = 18), ultrasonography (n = 17) and pathological findings. With respect to the primary tumour, FDG dual-head PET and CT revealed a sensitivity of 100% and 59%, respectively (P < 0.001). In seven patients lymph node metastases were found in the neck specimen. Two of them had bilateral metastases. FDG dual-head PET correctly identified all nine pathological neck sides whereas CT and ultrasonography depicted eight of nine and seven of eight pathological sides, respectively. In three patients, false-positive FDG uptake was seen, which was due to a preceding biopsy in two cases. The sensitivity of FDG dual-head PET, CT and ultrasonography in the identification of pathological neck sides was 100%, 89% and 87%, respectively, and the specificity was 90%, 93% and 50%, respectively. With knowledge of the preceding biopsies, the specificity of FDG dual-head PET would have been 97%. The smallest lymph node metastasis detected by FDG dual-head PET that was missed by CT had a diameter of 0.6 cm. Measurement of 18F-FDG with a dual-head PET camera is very sensitive in the detection of primary head and neck cancers and accurate in the preoperative assessment of lymph node metastases. The results justify a prospective study on the identification of metastases in patients with head and neck cancer. In addition, it is justified to start a study on the detection of unknown primary tumours in patients with cervical metastases.

Carcinoma, Squamous Cell↗
PubMed1999

Holmium-166 poly lactic acid microspheres applicable for intra-arterial radionuclide therapy of hepatic malignancies: effects of preparation and neutron activation techniques.

Since one of the most frequent sites of human metastatic cancer is the liver, particularly in colon and rectum carcinoma, there is a special need for the development of an effective therapy. This study describes the parameters for reproducible production of poly lactic acid (PLA) microspheres with an average diameter of 37 microm and labelled with neutron-activated holmium-166 (Emax=1.84 MeV, t1/2=26. 8 h), suitable for use in internal radionuclide therapy of liver metastases. It is demonstrated that holmium-loaded PLA microspheres can be prepared by a relatively simple method, with incorporation of 17.0%+/-0.6% holmium (n=5), and that 20 GBq can be obtained from 400 mg neutron activatable microspheres. In order to produce this high amount of activity, the microspheres must be free of water and irradiation must be performed in a polyethylene vial, with a relatively low neutron flux (5x10(13) cm-2 s-1) within 1 h. Under these well-defined conditions minor surface changes were seen which barely affected total volume and consequently total radioactivity of the microspheres with a diameter of 20-50 microm. Overall structural integrity was maintained in terms of form and size. In vitro analyses showed that >99.3% of 166Ho activity was retained in the microspheres after 192 h incubation in PBS, plasma and leucocytes, while in liver homogenate retention was still 98.4%.

Brachytherapy↗