Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1996
We prospectively studied the diagnostic potential of 201Tl and 99mTc-sestamibi (MIBI) SPECT for e... more We prospectively studied the diagnostic potential of 201Tl and 99mTc-sestamibi (MIBI) SPECT for evaluating the extent of primary disease and differentiating residual/recurrent disease from post-therapy changes in patients with nasopharyngeal carcinoma (NPC). Fifty patients (20 initial presentation, 30 post-therapy evaluation) underwent 201Tl and MIBI imaging. The findings were correlated with CT/MRI results. Tumor-to-background ratios were obtained. Biopsy confirmation (14 patients) and/or 6-12 mo clinical follow-up data (16 patients) were available in the post-therapy group. All primary disease sites were accurately detected by both imaging studies in the pretherapy group. However, MIBI-SPECT was superior to 201Tl SPECT (p = 0.0057) in detecting regional metastases (sensitivities of 95% versus 68%). In the post-therapy group, MIBI and 201Tl imaging were true-positive in 14 of 16 patients with proven residual/recurrent. In 17 patients who had no evidence of residual/recurrent tumor....
Objective: Choice and positioning of the prosthesis is a fundamental element in successful operat... more Objective: Choice and positioning of the prosthesis is a fundamental element in successful operations for otosclerosis. The present study compares two different techniques for placing a prosthesis when undertaking surgery for otosclerosis. Materials and Methods: A retrospective review was undertaken of records from 50 cases of individuals (33 women, 17 men) undergoing stapedotomy between the years 2009 and 2016. Two alternative procedures were used: in the “reverse” technique, placement of the prosthesis preceded stapes removal; in the “conventional” technique, placement of the prosthesis followed stapes removal. These groups were labeled groups 1 and 2, respectively. There were 25 cases in each. The two groups were compared for hearing outcome and incidence of complications. Results: An air-bone gap below 20 dB was obtained in 80% of cases following the reverse technique, and 76% of cases after conventional surgery. The difference between the two techniques lacked statistical significance (p>0.05). A single case in group 1 required a revision procedure since the prosthesis was taken out 4 months post-surgery. In group 2, a single case sustained an injury to the chorda tympani. Vertigo symptoms occurred in 7 individuals in group 1, and 8 in group 2. Conclusion: There is no significant difference between treatments in terms of improved auditory function or fewer complications. The authors suggest clinicians' experience is the key factor in deciding which technique to favor.
Kulak burun boğaz ihtisas dergisi : KBB = Journal of ear, nose, and throat
Primary squamous cell carcinoma of the nasal septum is an extremely rare malignancy. In this arti... more Primary squamous cell carcinoma of the nasal septum is an extremely rare malignancy. In this article, we report a case of 52-year-old female with a complaint of nasal obstruction along with occasional nasal bleeding for one year. Endoscopy showed a 2.5x2 cm perforation originating from the anterior nasal septum. Incisional biopsy result was reported as squamous cell carcinoma. The tumor was removed by functional endoscopic surgery. Histopathological examination revealed squamous cell carcinoma with safe surgery borders. No recurrence and complications were noticed after one year of follow-up. The functional impact of the treatment with high mortality rates highlights the importance of early diagnosis. We recommend the differential diagnosis of septal perforation and early wide surgical excision for such cases.
Frontal sinus back table fractures are seen rarely; also, typical presentation of frontal sinus e... more Frontal sinus back table fractures are seen rarely; also, typical presentation of frontal sinus encephalocele as a delayed complication of frontal sinus fracture is seen more rarely. We present a case of frontal encephalocele and recurrent meningitis as delayed complications of craniofacial trauma. Diagnosis, management, and treatment approaches of these complications are discussed.
Internal carotid artery (ICA) pseudoaneurysm is a rare complication of endoscopic endonasal surge... more Internal carotid artery (ICA) pseudoaneurysm is a rare complication of endoscopic endonasal surgery occurring in 0.4-1.1% of cases. Pseudoaneurysms can subsequently result in other complications, such as subarachnoid hemorrhage, epistaxis, and caroticocavernous fistula with resultant death or permanent neurologic deficit. In this case, we illustrate endovascular treatment with a flow-diverting stent for an ICA pseudoaneurysm after endoscopic endonasal surgery for a pituitary adenoma in a 56-year-old male. Surgery was complicated by excessive intraoperative bleeding and emergent CT angiography confirmed an iatrogenic pseudoaneurysm on the anteromedial surface of the ICA. The pseudoaneurysm was treated endovascularly with flow-diverting stent implantation only. Follow-up CT angiography after three months demonstrated occlusion of the pseudoaneurysm.
1. Nephron. 1993;63(3):363-4. Short-and long-term effects of felodipine on circulating endothelin... more 1. Nephron. 1993;63(3):363-4. Short-and long-term effects of felodipine on circulating endothelin and atrial natriuretic peptide levels in essential hypertension. Erbas B, Ozdemir O, Pasaoglu I, Ugur O, Varoglu E, Koray Z, Yorgancioglu C, Hazan E, Oram E, Bekdik CF. ...
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2006
In this study we hypothesized that if timing of gamma probe-guided parathyroidectomy were individ... more In this study we hypothesized that if timing of gamma probe-guided parathyroidectomy were individualized according to an optimal-time-to-surgery technique, in vivo characterization of parathyroid lesions would be possible. We compared our findings with an ex vivo counting method ("20% rule") and frozen section results. Thirty-five patients who were referred for surgical treatment of hyperparathyroidism were studied. Maximum parathyroid to thyroid sestamibi uptake ratio (UR(max)) was measured by use of preoperative dynamic scintigraphy. The interval between sestamibi injection and UR(max) was defined as the optimal time to surgery. On the day of surgery, the patients received the same dose of sestamibi and were taken to the operating room at UR(max) as determined by preoperative scintigraphy. Intraoperative in vivo gamma probe counts from parathyroid lesions were compared with in vivo contralateral background thyroid counts (in vivo/Bkg) and to ex vivo parathyroid counts re...
Hepatic artery perfusion scintigraphy is a routine procedure for patient evaluation before Y-90 r... more Hepatic artery perfusion scintigraphy is a routine procedure for patient evaluation before Y-90 radiomicrosphere therapy and mostly used for prediction of extrahepatic leakage. Moreover, it also displays perfusion pattern of tumours, which is an important parameter on success of the therapy. The aim of this study is to assess the relation between the perfusion pattern on hepatic artery perfusion scintigraphy and radiomicrosphere therapy response. A total of 99 radiomicrosphere therapy applications were carried out in 80 patients (M/F: 55/25). Heterogeneous and diffuse perfusion patterns were observed in 47 patients and 52 patients, respectively. The patients with diffuse perfusion pattern had better therapy response both on FDG PET/CT (p= 0.04) and CT (p=0.008) when compared to those with heterogenous perfusion pattern. Perfusion pattern observed on hepatic artery perfusion scintigraphy may be a successful predictor of early response to radiomicrosphere therapy. None declared.
Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Th... more Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for The Endocrinologist. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is ...
Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Nuclear Medicine ... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Nuclear Medicine Communications. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is ...
Medullary thyroid cancer (MTC) originates from parafollicular C cells of the thyroid and accounts... more Medullary thyroid cancer (MTC) originates from parafollicular C cells of the thyroid and accounts for 3-12% of all thyroid cancers. As opposed to other types of dedifferentiated thyroid tumours, MTC cells are highly functional, producing and secreting high amounts of calcitonin and carcinoembryonic antigen. As parafollicular C cells are of neural crest origin, MTC acts as a neuroendocrine tumour also and expresses somatostatin receptors. Although conventional radiological methods such as ultrasonography, computed tomography and magnetic resonance imaging are widely used in the primary diagnosis and staging, they often fail to localize the residual or recurrent disease because the majority of MTC recurrence presents as occult disease. Thus, owing to functional characteristics of MTC, functional imaging modalities of nuclear medicine play a major role in the diagnostic and therapeutic strategies for MTC. Among nuclear medicine modalities, Tc(V) -dimercaptosuccinic acid, In-octreotide and I/I-meta-iodobenzylguanidine are commonly used in the diagnostic and even more in postoperative work-up of MTC. Alternatively, F-fluorodeoxyglucose and other positron emission tomography radiopharmaceuticals such as F-fluorodopa or F-fluorodopamine as well as radiolabelled antibodies such as Tc/I/I anticarcinoembryonic antigen, antigastrin, and anticholecystokinin-B have promising results. Functional imaging has a great advantage for nuclear medicine techniques in the routine work-up of MTC patients and also has a wide use in experimental studies.
The initial treatment of differentiated thyroid cancer is thyroidectomy, followed by remnant abla... more The initial treatment of differentiated thyroid cancer is thyroidectomy, followed by remnant ablation with iodine-131 (I-131) in some patients. However, controversy exists concerning the appropriate radioiodine dose. The aim of the study is to compare the success rate of low and high activities of I-131 for postoperative remnant ablation. A total of 108 nonmetastatic low-risk patients (mean age: 46, 85% women) with papillary and follicular carcinoma had I-131 ablation for the postoperative thyroid remnant. Fifty-three patients received a low dose (L) (800 MBq) and 55 patients received a high dose (H) (3700 MBq) of I-131. After total thyroidectomy, thyroid bed I-131 uptake (RAIU) and neck ultrasonography (USG) were performed to determine the remnant volume and the iodine avidity, which were used to calculate the dose delivered to the remnant tissue. The success rate of I-131 ablation was assessed with four different criteria based on serum thyroglobulin (Tg) and USG with and without the utilization of I-131 diagnostic whole-body scintigraphy (DxWBS). Ablation was considered to be successful if patients fulfilled all of the following criteria. (a) Strict criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or up to 0.2% RAIU, and (iii) Tg < 0.2 ng/ml; (b) lax criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or ≤ 0.2% RAIU, and (iii) Tg < 2 ng/ml; (c) strict criteria based on two tests: (i) USG negative and (ii) Tg < 0.2 ng/ml; (d) lax criteria based on two test: (i) USG negative and (ii) Tg < 2 ng/ml. When three tests were used to define successful ablation, in group L, 32 out of 53 (60%) and 43 out of 53 (81%) patients were successfully treated versus 35 out of 55 (64%) and 42 out of 55 (76%) for group H on the basis of strict and lax criteria, respectively (P=NS). The differences were not statistically significant between the two groups when only two tests were used to define ablation success (62 vs. 69% with strict and 89 vs. 87% with lax criteria, respectively). Our findings suggest that remnant thyroid tissue in patients with low-risk, well-differentiated thyroid cancer after total thyroidectomy can be ablated with 800 MBq of I-131. The success rate is not different from that obtained with 3700 MBq I-131.
To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combination... more To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combinations should be used to deliver the highest tumor and the lowest normal tissue doses. In a mouse model, tumor and critical organ-absorbed doses delivered by different radioimmunoconjugates were calculated and compared. We used a Medical Internal Radiation Dosimetry (MIRD)-style mouse dosimetry model that incorporates cross-organ beta doses to make refined estimates of the radiation absorbed dose to tissues. Biodistribution data from neuroblastoma xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed dose values for 90Y-3F8, 131I-3F8 and 131I-F(ab')2 fragments. Immunoreactive fractions of the radiolabeled antibodies were comparable. Although tumor uptake of the radioiodinated and radiometal labeled 3F8 was much higher than that of the radioiodinated F(ab')2 fragments (maximum percent injected dose per gram values were 39.4, 33.2 and 20.1 for 131I-3F8, 90Y-3F8 and 131I-F(ab')2, respectively), tumor to nontumor ratios were higher for radioiodinated fragments (with the exception of tumor to kidney ratio). For the minimum tumor dose necessary for complete ablation, the bone marrow received 195, 278 and 401 cGy for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor doses were 50.1, 232 and 992 cGy/MBq for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor to bone marrow dose, which is defined as the therapeutic index, was 21.5, 14.7 and 10.4 for 131I-F(ab')2, 131I-3F8 and 90Y-3F8. 131I-F(ab')2 fragments produced the highest therapeutic index but also the lowest tumor dose for radioimmunotherapy. Radiometal conjugated IgG produced the highest tumor dose but also the lowest therapeutic index.
Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expre... more Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe1-Tyr3-octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T(1/2) =9.5 hr; beta+=56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of 66Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with 67Ga- and 68Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was > 95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0 +/- 0.7, 13.2 +/- 2.1 and 9.8 +/- 1.5 for 66Ga-, 67Ga-, and 68Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for 66Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that 66Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. 66Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the critical organ for toxicity (tumor/kidney ratio = 1.64), and high kidney uptake must be eliminated before devising a therapy protocol.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1996
We prospectively studied the diagnostic potential of 201Tl and 99mTc-sestamibi (MIBI) SPECT for e... more We prospectively studied the diagnostic potential of 201Tl and 99mTc-sestamibi (MIBI) SPECT for evaluating the extent of primary disease and differentiating residual/recurrent disease from post-therapy changes in patients with nasopharyngeal carcinoma (NPC). Fifty patients (20 initial presentation, 30 post-therapy evaluation) underwent 201Tl and MIBI imaging. The findings were correlated with CT/MRI results. Tumor-to-background ratios were obtained. Biopsy confirmation (14 patients) and/or 6-12 mo clinical follow-up data (16 patients) were available in the post-therapy group. All primary disease sites were accurately detected by both imaging studies in the pretherapy group. However, MIBI-SPECT was superior to 201Tl SPECT (p = 0.0057) in detecting regional metastases (sensitivities of 95% versus 68%). In the post-therapy group, MIBI and 201Tl imaging were true-positive in 14 of 16 patients with proven residual/recurrent. In 17 patients who had no evidence of residual/recurrent tumor....
Objective: Choice and positioning of the prosthesis is a fundamental element in successful operat... more Objective: Choice and positioning of the prosthesis is a fundamental element in successful operations for otosclerosis. The present study compares two different techniques for placing a prosthesis when undertaking surgery for otosclerosis. Materials and Methods: A retrospective review was undertaken of records from 50 cases of individuals (33 women, 17 men) undergoing stapedotomy between the years 2009 and 2016. Two alternative procedures were used: in the “reverse” technique, placement of the prosthesis preceded stapes removal; in the “conventional” technique, placement of the prosthesis followed stapes removal. These groups were labeled groups 1 and 2, respectively. There were 25 cases in each. The two groups were compared for hearing outcome and incidence of complications. Results: An air-bone gap below 20 dB was obtained in 80% of cases following the reverse technique, and 76% of cases after conventional surgery. The difference between the two techniques lacked statistical significance (p>0.05). A single case in group 1 required a revision procedure since the prosthesis was taken out 4 months post-surgery. In group 2, a single case sustained an injury to the chorda tympani. Vertigo symptoms occurred in 7 individuals in group 1, and 8 in group 2. Conclusion: There is no significant difference between treatments in terms of improved auditory function or fewer complications. The authors suggest clinicians' experience is the key factor in deciding which technique to favor.
Kulak burun boğaz ihtisas dergisi : KBB = Journal of ear, nose, and throat
Primary squamous cell carcinoma of the nasal septum is an extremely rare malignancy. In this arti... more Primary squamous cell carcinoma of the nasal septum is an extremely rare malignancy. In this article, we report a case of 52-year-old female with a complaint of nasal obstruction along with occasional nasal bleeding for one year. Endoscopy showed a 2.5x2 cm perforation originating from the anterior nasal septum. Incisional biopsy result was reported as squamous cell carcinoma. The tumor was removed by functional endoscopic surgery. Histopathological examination revealed squamous cell carcinoma with safe surgery borders. No recurrence and complications were noticed after one year of follow-up. The functional impact of the treatment with high mortality rates highlights the importance of early diagnosis. We recommend the differential diagnosis of septal perforation and early wide surgical excision for such cases.
Frontal sinus back table fractures are seen rarely; also, typical presentation of frontal sinus e... more Frontal sinus back table fractures are seen rarely; also, typical presentation of frontal sinus encephalocele as a delayed complication of frontal sinus fracture is seen more rarely. We present a case of frontal encephalocele and recurrent meningitis as delayed complications of craniofacial trauma. Diagnosis, management, and treatment approaches of these complications are discussed.
Internal carotid artery (ICA) pseudoaneurysm is a rare complication of endoscopic endonasal surge... more Internal carotid artery (ICA) pseudoaneurysm is a rare complication of endoscopic endonasal surgery occurring in 0.4-1.1% of cases. Pseudoaneurysms can subsequently result in other complications, such as subarachnoid hemorrhage, epistaxis, and caroticocavernous fistula with resultant death or permanent neurologic deficit. In this case, we illustrate endovascular treatment with a flow-diverting stent for an ICA pseudoaneurysm after endoscopic endonasal surgery for a pituitary adenoma in a 56-year-old male. Surgery was complicated by excessive intraoperative bleeding and emergent CT angiography confirmed an iatrogenic pseudoaneurysm on the anteromedial surface of the ICA. The pseudoaneurysm was treated endovascularly with flow-diverting stent implantation only. Follow-up CT angiography after three months demonstrated occlusion of the pseudoaneurysm.
1. Nephron. 1993;63(3):363-4. Short-and long-term effects of felodipine on circulating endothelin... more 1. Nephron. 1993;63(3):363-4. Short-and long-term effects of felodipine on circulating endothelin and atrial natriuretic peptide levels in essential hypertension. Erbas B, Ozdemir O, Pasaoglu I, Ugur O, Varoglu E, Koray Z, Yorgancioglu C, Hazan E, Oram E, Bekdik CF. ...
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2006
In this study we hypothesized that if timing of gamma probe-guided parathyroidectomy were individ... more In this study we hypothesized that if timing of gamma probe-guided parathyroidectomy were individualized according to an optimal-time-to-surgery technique, in vivo characterization of parathyroid lesions would be possible. We compared our findings with an ex vivo counting method ("20% rule") and frozen section results. Thirty-five patients who were referred for surgical treatment of hyperparathyroidism were studied. Maximum parathyroid to thyroid sestamibi uptake ratio (UR(max)) was measured by use of preoperative dynamic scintigraphy. The interval between sestamibi injection and UR(max) was defined as the optimal time to surgery. On the day of surgery, the patients received the same dose of sestamibi and were taken to the operating room at UR(max) as determined by preoperative scintigraphy. Intraoperative in vivo gamma probe counts from parathyroid lesions were compared with in vivo contralateral background thyroid counts (in vivo/Bkg) and to ex vivo parathyroid counts re...
Hepatic artery perfusion scintigraphy is a routine procedure for patient evaluation before Y-90 r... more Hepatic artery perfusion scintigraphy is a routine procedure for patient evaluation before Y-90 radiomicrosphere therapy and mostly used for prediction of extrahepatic leakage. Moreover, it also displays perfusion pattern of tumours, which is an important parameter on success of the therapy. The aim of this study is to assess the relation between the perfusion pattern on hepatic artery perfusion scintigraphy and radiomicrosphere therapy response. A total of 99 radiomicrosphere therapy applications were carried out in 80 patients (M/F: 55/25). Heterogeneous and diffuse perfusion patterns were observed in 47 patients and 52 patients, respectively. The patients with diffuse perfusion pattern had better therapy response both on FDG PET/CT (p= 0.04) and CT (p=0.008) when compared to those with heterogenous perfusion pattern. Perfusion pattern observed on hepatic artery perfusion scintigraphy may be a successful predictor of early response to radiomicrosphere therapy. None declared.
Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Th... more Advertisement. Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for The Endocrinologist. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is ...
Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Nuclear Medicine ... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for Nuclear Medicine Communications. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is ...
Medullary thyroid cancer (MTC) originates from parafollicular C cells of the thyroid and accounts... more Medullary thyroid cancer (MTC) originates from parafollicular C cells of the thyroid and accounts for 3-12% of all thyroid cancers. As opposed to other types of dedifferentiated thyroid tumours, MTC cells are highly functional, producing and secreting high amounts of calcitonin and carcinoembryonic antigen. As parafollicular C cells are of neural crest origin, MTC acts as a neuroendocrine tumour also and expresses somatostatin receptors. Although conventional radiological methods such as ultrasonography, computed tomography and magnetic resonance imaging are widely used in the primary diagnosis and staging, they often fail to localize the residual or recurrent disease because the majority of MTC recurrence presents as occult disease. Thus, owing to functional characteristics of MTC, functional imaging modalities of nuclear medicine play a major role in the diagnostic and therapeutic strategies for MTC. Among nuclear medicine modalities, Tc(V) -dimercaptosuccinic acid, In-octreotide and I/I-meta-iodobenzylguanidine are commonly used in the diagnostic and even more in postoperative work-up of MTC. Alternatively, F-fluorodeoxyglucose and other positron emission tomography radiopharmaceuticals such as F-fluorodopa or F-fluorodopamine as well as radiolabelled antibodies such as Tc/I/I anticarcinoembryonic antigen, antigastrin, and anticholecystokinin-B have promising results. Functional imaging has a great advantage for nuclear medicine techniques in the routine work-up of MTC patients and also has a wide use in experimental studies.
The initial treatment of differentiated thyroid cancer is thyroidectomy, followed by remnant abla... more The initial treatment of differentiated thyroid cancer is thyroidectomy, followed by remnant ablation with iodine-131 (I-131) in some patients. However, controversy exists concerning the appropriate radioiodine dose. The aim of the study is to compare the success rate of low and high activities of I-131 for postoperative remnant ablation. A total of 108 nonmetastatic low-risk patients (mean age: 46, 85% women) with papillary and follicular carcinoma had I-131 ablation for the postoperative thyroid remnant. Fifty-three patients received a low dose (L) (800 MBq) and 55 patients received a high dose (H) (3700 MBq) of I-131. After total thyroidectomy, thyroid bed I-131 uptake (RAIU) and neck ultrasonography (USG) were performed to determine the remnant volume and the iodine avidity, which were used to calculate the dose delivered to the remnant tissue. The success rate of I-131 ablation was assessed with four different criteria based on serum thyroglobulin (Tg) and USG with and without the utilization of I-131 diagnostic whole-body scintigraphy (DxWBS). Ablation was considered to be successful if patients fulfilled all of the following criteria. (a) Strict criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or up to 0.2% RAIU, and (iii) Tg < 0.2 ng/ml; (b) lax criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or ≤ 0.2% RAIU, and (iii) Tg < 2 ng/ml; (c) strict criteria based on two tests: (i) USG negative and (ii) Tg < 0.2 ng/ml; (d) lax criteria based on two test: (i) USG negative and (ii) Tg < 2 ng/ml. When three tests were used to define successful ablation, in group L, 32 out of 53 (60%) and 43 out of 53 (81%) patients were successfully treated versus 35 out of 55 (64%) and 42 out of 55 (76%) for group H on the basis of strict and lax criteria, respectively (P=NS). The differences were not statistically significant between the two groups when only two tests were used to define ablation success (62 vs. 69% with strict and 89 vs. 87% with lax criteria, respectively). Our findings suggest that remnant thyroid tissue in patients with low-risk, well-differentiated thyroid cancer after total thyroidectomy can be ablated with 800 MBq of I-131. The success rate is not different from that obtained with 3700 MBq I-131.
To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combination... more To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combinations should be used to deliver the highest tumor and the lowest normal tissue doses. In a mouse model, tumor and critical organ-absorbed doses delivered by different radioimmunoconjugates were calculated and compared. We used a Medical Internal Radiation Dosimetry (MIRD)-style mouse dosimetry model that incorporates cross-organ beta doses to make refined estimates of the radiation absorbed dose to tissues. Biodistribution data from neuroblastoma xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed dose values for 90Y-3F8, 131I-3F8 and 131I-F(ab')2 fragments. Immunoreactive fractions of the radiolabeled antibodies were comparable. Although tumor uptake of the radioiodinated and radiometal labeled 3F8 was much higher than that of the radioiodinated F(ab')2 fragments (maximum percent injected dose per gram values were 39.4, 33.2 and 20.1 for 131I-3F8, 90Y-3F8 and 131I-F(ab')2, respectively), tumor to nontumor ratios were higher for radioiodinated fragments (with the exception of tumor to kidney ratio). For the minimum tumor dose necessary for complete ablation, the bone marrow received 195, 278 and 401 cGy for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor doses were 50.1, 232 and 992 cGy/MBq for 131I-F(ab')2, 131I-3F8 and 90Y-3F8, respectively. Tumor to bone marrow dose, which is defined as the therapeutic index, was 21.5, 14.7 and 10.4 for 131I-F(ab')2, 131I-3F8 and 90Y-3F8. 131I-F(ab')2 fragments produced the highest therapeutic index but also the lowest tumor dose for radioimmunotherapy. Radiometal conjugated IgG produced the highest tumor dose but also the lowest therapeutic index.
Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expre... more Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe1-Tyr3-octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T(1/2) =9.5 hr; beta+=56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of 66Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with 67Ga- and 68Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was > 95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0 +/- 0.7, 13.2 +/- 2.1 and 9.8 +/- 1.5 for 66Ga-, 67Ga-, and 68Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for 66Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that 66Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. 66Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the critical organ for toxicity (tumor/kidney ratio = 1.64), and high kidney uptake must be eliminated before devising a therapy protocol.
Uploads
Papers by Omer Ugur