M. Keyaerts - Academia.edu (original) (raw)
Papers by M. Keyaerts
Journal of Nuclear Medicine, 2013
Nanobodies are the smallest fully functional antigen-binding antibody fragments possessing ideal ... more Nanobodies are the smallest fully functional antigen-binding antibody fragments possessing ideal properties as probes for molecular imaging. In this study we labeled the anti-human epidermal growth factor receptor type 2 (HER2) Nanobody with 68 Ga via a 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) derivative and assessed its use for HER2 iPET imaging. Methods: The 2Rs15dHis 6 Nanobody and the lead optimized current-good-manufacturing-practice grade analog 2Rs15d were conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) to enable fast and efficient 68 Ga labeling. Biodistribution and PET/CT studies were performed on HER2-positive and -negative tumor xenografts. The effect of injected mass on biodistribution was evaluated. The biodistribution data were extrapolated to calculate radiation dose estimates for the adult female using OLINDA software. A single-dose extended-toxicity study for NOTA-2Rs15d was performed on healthy mice up to a dose of 10 mg/kg. Results: Radiolabeling was quantitative (.97%) after 5 min of incubation at room temperature; specific activity was 55-200 MBq/nmol. Biodistribution studies showed fast and specific uptake (percentage injected activity [%IA]) in HER2positive tumors (3.13 6 0.06 and 4.34 6 0.90 %IA/g for 68 Ga-NOTA-2Rs15dHis 6 and 68 Ga-NOTA-2Rs15d, respectively, at 1 h after injection) and high tumor-to-blood and tumor-to-muscle ratios at 1 h after injection, resulting in high-contrast PET/CT images with high specific tumor uptake. A remarkable finding of the biodistribution studies was that kidney uptake was reduced by 60% for the Nanobody lacking the C-terminal His 6 tag. The injected mass showed an effect on the general biodistribution: a 100-fold increase in NOTA-2Rs15d mass decreased liver uptake from 7.43 6 1.89 to 2.90 6 0.26 %IA/g whereas tumor uptake increased from 2.49 6 0.68 to 4.23 6 0.99 %IA/g. The calculated effective dose, based on extrapolation of mouse data, was 0.0218 mSv/MBq, which would yield a radiation dose of 4 mSv to a patient after injection of 185 MBq of 68 Ga-NOTA-2Rs15d. In the toxicity study, no adverse effects were observed after injection of a 10 mg/kg dose of NOTA-2Rs15d.
JBR-BTR : organe de la Société royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR)
JBR-BTR : organe de la Société royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR)
JBR-BTR : organe de la Société royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR)
Erdheim-Chester disease (ECD) is a rare non-Langerhans' cell histiocytosis. Mild but permanen... more Erdheim-Chester disease (ECD) is a rare non-Langerhans' cell histiocytosis. Mild but permanent juxta-articular bone pain in mainly knees and ankles is the most frequent associated symptom. Despite the pathognomonic radiographic findings, most cases are still diagnosed by the pathologist.The lesions consist of lipid-storing CD 68 +/CD 1a--non-Langerhans' cell histiocytes, most frequently localized in bone but also involving multiple organ systems in the body. We present a case report in which the diagnosis of ECD was established with 99mTc MDP bone SPECT/CT.
Nuclear Medicine Communications, 2007
Several authors have shown in animal studies that D-enantiomeric amino acid analogues can have be... more Several authors have shown in animal studies that D-enantiomeric amino acid analogues can have better tumour imaging properties compared to their L-analogues. In our group, the D and L isomers of 2-[I]iodo-phenylalanine were identified as tumour-specific tracers in rat and mouse tumour models, with an advantage for the D-isomer. Here we compare, intra-individually, the normal biodistribution and dosimetry of both tracers in healthy human subjects. Five male volunteers received both the L- and D-enantiomers, ranging from 84 to 114 MBq, with a 1 week interval between the tracers, allowing intra-individual comparison. Whole-body scans were performed and blood and urine samples were collected and analysed up to 24 h. Dosimetry was calculated using OLINDA 1.0 software. The biodistributions of the tracers are comparable as both show a moderate uptake in heart and the liver, a marked uptake in muscle tissue and clearance via the renal system. However, due to faster clearance, from 2.5 h, the uptake of the D-enantiomer was significantly lower compared to the L-isomer in all organs. The radiation dose estimations showed an effective dose of, respectively, 0.0120+/-0.0020 mSv x Bq(-1) and 0.0106+/-0.0038 mSv x Bq(-1) for 2-123I-L-Phe and 2-123I-D-Phe (P=0.18). In both cases the organ receiving the highest dose was the bladder wall. Both 2-123I-L-Phe and 2-123I-D-Phe show comparable moderate uptake in all organs. 2-123I-D-Phe is the more promising tracer, as it shows a faster clearance resulting in a lower dose and a lower background, favouring tumour imaging with respect to the tumour/background ratio.
Journal of Nuclear Medicine, 2008
European Journal of Nuclear Medicine and Molecular Imaging, 2007
Purpose 123 I-2-iodo-tyrosine ( 123 I-2IT) has been identified as a promising new amino acid trac... more Purpose 123 I-2-iodo-tyrosine ( 123 I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. Methods For the biodistribution study, six male volunteers received 60-95 MBq 123 I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of 123 I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumourto-background (T/B) ratios were calculated for semiquantitative analysis. The results were correlated with clinical and MRI follow-up data or histology.
Journal of Nuclear Medicine, 2015
The HER2-status is one of the major tumor characteristics in breast cancer to guide therapy. Anti... more The HER2-status is one of the major tumor characteristics in breast cancer to guide therapy. Anti-HER2 treatment has clear survival advantages in HER2-positive breast carcinoma patients. Heterogeneity in HER2 expression has repeatedly been described between primary tumor and metastasis, resulting in the need to reassess HER2-status during the disease course. In order to avoid repeated biopsy with potential bias due to tumor heterogeneity, nanobodies directed against HER2 have been developed as probes for molecular imaging. Nanobodies are the smallest antigen-binding antibody fragments derived from unique heavy-chain-only antibodies, with ideal characteristics for positron emission tomography (PET) imaging. the primary aims were assessment of safety, biodistribution and dosimetry. The secondary aim was to investigate tumor targeting potential. In total, 20 female patients with primary or metastatic breast carcinoma (HER2 IHC 2+ or 3+) were included. Anti-HER2 Nanobody is labeled with (68)Ga via a NOTA derivative. Administered activities were 53-174 MBq (average 107 MBq). PET/CT scans (for dosimetry assessment) were obtained at 10, 60 and 90 min post administration. Physical evaluation and blood analysis were performed for safety evaluation. Biodistribution was analyzed for 11 organs using MIM software; dosimetry was assessed using OLINDA/EXM. Tumor targeting potential was assessed in primary and metastatic lesions. No adverse reactions occurred. A fast blood clearance was observed, with only 10% of injected activity remaining in the blood at 1h post injection. Uptake was mainly seen in kidneys, liver, and intestines. The effective dose was 0.043 mSv/MBq, resulting in an average of 4.6 mSv per patient. The critical organ was the urinary bladder wall with a dose of 0.406 mGy/MBq. In patients with metastatic disease, tracer accumulation well above background was demonstrated in the majority of identified sites of disease. Primary lesions were more variable in tracer accumulation. (68)Ga--HER2-Nanobody PET/CT is a safe procedure with a radiation dose comparable to other routinely used PET tracers. Its biodistribution is favorable, with the highest uptake in kidneys, liver and intestines, but very low background levels in all other organs that typically house primary breast carcinoma or tumor metastasis. Tracer accumulation in HER2-positive metastases is high, compared to normal surrounding tissues, and warrants further assessment in a phase II trial.
Journal of Nuclear Medicine, 2013
Nanobodies are the smallest fully functional antigen-binding antibody fragments possessing ideal ... more Nanobodies are the smallest fully functional antigen-binding antibody fragments possessing ideal properties as probes for molecular imaging. In this study we labeled the anti-human epidermal growth factor receptor type 2 (HER2) Nanobody with 68 Ga via a 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) derivative and assessed its use for HER2 iPET imaging. Methods: The 2Rs15dHis 6 Nanobody and the lead optimized current-good-manufacturing-practice grade analog 2Rs15d were conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) to enable fast and efficient 68 Ga labeling. Biodistribution and PET/CT studies were performed on HER2-positive and -negative tumor xenografts. The effect of injected mass on biodistribution was evaluated. The biodistribution data were extrapolated to calculate radiation dose estimates for the adult female using OLINDA software. A single-dose extended-toxicity study for NOTA-2Rs15d was performed on healthy mice up to a dose of 10 mg/kg. Results: Radiolabeling was quantitative (.97%) after 5 min of incubation at room temperature; specific activity was 55-200 MBq/nmol. Biodistribution studies showed fast and specific uptake (percentage injected activity [%IA]) in HER2positive tumors (3.13 6 0.06 and 4.34 6 0.90 %IA/g for 68 Ga-NOTA-2Rs15dHis 6 and 68 Ga-NOTA-2Rs15d, respectively, at 1 h after injection) and high tumor-to-blood and tumor-to-muscle ratios at 1 h after injection, resulting in high-contrast PET/CT images with high specific tumor uptake. A remarkable finding of the biodistribution studies was that kidney uptake was reduced by 60% for the Nanobody lacking the C-terminal His 6 tag. The injected mass showed an effect on the general biodistribution: a 100-fold increase in NOTA-2Rs15d mass decreased liver uptake from 7.43 6 1.89 to 2.90 6 0.26 %IA/g whereas tumor uptake increased from 2.49 6 0.68 to 4.23 6 0.99 %IA/g. The calculated effective dose, based on extrapolation of mouse data, was 0.0218 mSv/MBq, which would yield a radiation dose of 4 mSv to a patient after injection of 185 MBq of 68 Ga-NOTA-2Rs15d. In the toxicity study, no adverse effects were observed after injection of a 10 mg/kg dose of NOTA-2Rs15d.
JBR-BTR : organe de la Société royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR)
JBR-BTR : organe de la Société royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR)
JBR-BTR : organe de la Société royale belge de radiologie (SRBR) = orgaan van de Koninklijke Belgische Vereniging voor Radiologie (KBVR)
Erdheim-Chester disease (ECD) is a rare non-Langerhans' cell histiocytosis. Mild but permanen... more Erdheim-Chester disease (ECD) is a rare non-Langerhans' cell histiocytosis. Mild but permanent juxta-articular bone pain in mainly knees and ankles is the most frequent associated symptom. Despite the pathognomonic radiographic findings, most cases are still diagnosed by the pathologist.The lesions consist of lipid-storing CD 68 +/CD 1a--non-Langerhans' cell histiocytes, most frequently localized in bone but also involving multiple organ systems in the body. We present a case report in which the diagnosis of ECD was established with 99mTc MDP bone SPECT/CT.
Nuclear Medicine Communications, 2007
Several authors have shown in animal studies that D-enantiomeric amino acid analogues can have be... more Several authors have shown in animal studies that D-enantiomeric amino acid analogues can have better tumour imaging properties compared to their L-analogues. In our group, the D and L isomers of 2-[I]iodo-phenylalanine were identified as tumour-specific tracers in rat and mouse tumour models, with an advantage for the D-isomer. Here we compare, intra-individually, the normal biodistribution and dosimetry of both tracers in healthy human subjects. Five male volunteers received both the L- and D-enantiomers, ranging from 84 to 114 MBq, with a 1 week interval between the tracers, allowing intra-individual comparison. Whole-body scans were performed and blood and urine samples were collected and analysed up to 24 h. Dosimetry was calculated using OLINDA 1.0 software. The biodistributions of the tracers are comparable as both show a moderate uptake in heart and the liver, a marked uptake in muscle tissue and clearance via the renal system. However, due to faster clearance, from 2.5 h, the uptake of the D-enantiomer was significantly lower compared to the L-isomer in all organs. The radiation dose estimations showed an effective dose of, respectively, 0.0120+/-0.0020 mSv x Bq(-1) and 0.0106+/-0.0038 mSv x Bq(-1) for 2-123I-L-Phe and 2-123I-D-Phe (P=0.18). In both cases the organ receiving the highest dose was the bladder wall. Both 2-123I-L-Phe and 2-123I-D-Phe show comparable moderate uptake in all organs. 2-123I-D-Phe is the more promising tracer, as it shows a faster clearance resulting in a lower dose and a lower background, favouring tumour imaging with respect to the tumour/background ratio.
Journal of Nuclear Medicine, 2008
European Journal of Nuclear Medicine and Molecular Imaging, 2007
Purpose 123 I-2-iodo-tyrosine ( 123 I-2IT) has been identified as a promising new amino acid trac... more Purpose 123 I-2-iodo-tyrosine ( 123 I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. Methods For the biodistribution study, six male volunteers received 60-95 MBq 123 I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of 123 I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumourto-background (T/B) ratios were calculated for semiquantitative analysis. The results were correlated with clinical and MRI follow-up data or histology.
Journal of Nuclear Medicine, 2015
The HER2-status is one of the major tumor characteristics in breast cancer to guide therapy. Anti... more The HER2-status is one of the major tumor characteristics in breast cancer to guide therapy. Anti-HER2 treatment has clear survival advantages in HER2-positive breast carcinoma patients. Heterogeneity in HER2 expression has repeatedly been described between primary tumor and metastasis, resulting in the need to reassess HER2-status during the disease course. In order to avoid repeated biopsy with potential bias due to tumor heterogeneity, nanobodies directed against HER2 have been developed as probes for molecular imaging. Nanobodies are the smallest antigen-binding antibody fragments derived from unique heavy-chain-only antibodies, with ideal characteristics for positron emission tomography (PET) imaging. the primary aims were assessment of safety, biodistribution and dosimetry. The secondary aim was to investigate tumor targeting potential. In total, 20 female patients with primary or metastatic breast carcinoma (HER2 IHC 2+ or 3+) were included. Anti-HER2 Nanobody is labeled with (68)Ga via a NOTA derivative. Administered activities were 53-174 MBq (average 107 MBq). PET/CT scans (for dosimetry assessment) were obtained at 10, 60 and 90 min post administration. Physical evaluation and blood analysis were performed for safety evaluation. Biodistribution was analyzed for 11 organs using MIM software; dosimetry was assessed using OLINDA/EXM. Tumor targeting potential was assessed in primary and metastatic lesions. No adverse reactions occurred. A fast blood clearance was observed, with only 10% of injected activity remaining in the blood at 1h post injection. Uptake was mainly seen in kidneys, liver, and intestines. The effective dose was 0.043 mSv/MBq, resulting in an average of 4.6 mSv per patient. The critical organ was the urinary bladder wall with a dose of 0.406 mGy/MBq. In patients with metastatic disease, tracer accumulation well above background was demonstrated in the majority of identified sites of disease. Primary lesions were more variable in tracer accumulation. (68)Ga--HER2-Nanobody PET/CT is a safe procedure with a radiation dose comparable to other routinely used PET tracers. Its biodistribution is favorable, with the highest uptake in kidneys, liver and intestines, but very low background levels in all other organs that typically house primary breast carcinoma or tumor metastasis. Tracer accumulation in HER2-positive metastases is high, compared to normal surrounding tissues, and warrants further assessment in a phase II trial.