OBJECTIVE The aim of the present study was to perform calculation of the absorbed doses to organs... more OBJECTIVE The aim of the present study was to perform calculation of the absorbed doses to organs at risk and to neuroendocrine tumors and to determine whether hepatic intra-arterial (IA) injection of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) would achieve higher intratumoral concentrations than standard intravenous administration of 177Lu-DOTATATE. METHODS 29 patients with Grade I-II, inoperable, metastatic gastro-entero-pancreatic neuroendocrine tumor (GEPNET) were prospectively identified and enrolled for the study. 15 patients of GEPNETs with liver-dominant metastatic disease and less than 3 sites of extrahepatic metastatic disease were administered a single dose of 177Lu-DOTATATE therapy through the selective catheterization of the hepatic artery (IA group). The other 14 patients received a single dose of 177 Lu- DOTATATE through standard intravenous route (IV group). For dosimetry, whole-body γ (anterior and posterior planar acquisitions) and SPECT/CT scans of the abdomen at 2, 24 and 96 h post 177Lu-DOTATATE administration were acquired. Dosimetric calculations were done using the HERMES software. RESULTS The mean dose per unit activity (DpA) in the liver and tumor lesions in the IA group differed significantly (p < 0.05) but differed insignificantly in spleen and kidneys (p > 05) with the IV group. The mean tumor/non-tumor concentration at 96 h was 76.83 ± 7.9 (range 10.2-251.3) in the IA group whereas it was 25.6 ± 5.9 (Range: 12-55) in the IV group. There was an average threefold increase in tumoral concentration over the standard intravenous group. CONCLUSION IA administration of 177Lu-DOTATATE results in higher concentration and absorbed dose in hepatic metastases in patients of GEPNETs as compared to a single dose of PRRT administered through standard IV route, and thus seems to be a powerful tool to improve the efficacy of PRRT. ADVANCES IN KNOWLEDGE Measurement of the dose received by the tumor lesions and the critical organs is of paramount importance for the prognostication of a radionuclide therapy. Scant data exist on the dosimetric impact of IA administration of the therapy with 177Lu-DOTATATE on the tumors and other organs, and this study would add an impact towards the better treatment outcome in patients of neuroendocrine tumor with liver-dominant metastatic disease.
Nuclear Medicine and Molecular Imaging, Sep 10, 2021
Laparoscopic resection of tumor is often performed for benign and small insulinomas, or for those... more Laparoscopic resection of tumor is often performed for benign and small insulinomas, or for those located in the body or tail of the pancreas. The precise preoperative and intraoperative localization of the insulinoma is critical to minimize the surgical intervention. Conventional imaging studies, i.e., MRI, CT, and endoscopic ultrasound have limited sensitivity due to the small size of the insulinomas. Angiography, intraarterial calcium stimulation, and venous sampling are invasive procedures with concomitant risk for complications. Exendin-4 PET/CT scan has shown to be of great value in preoperative localization of insulinomas. In the absence of the traditional gold standard, i.e., intraoperative ultrasound with manual palpation, in laparoscopic surgery, a simple enucleation procedure might not be possible. Gamma probe-assisted surgery is a new method of diagnosis and treatment which allows a small area of tissue to be identified and removed, while a large area of the organ or the system remains unaffected. We present a case of a 34-year-old man with clinical suspicion of insulinoma with negative conventional imaging and successful lesion localization with 68Ga-Exendin-4 PET/CT scan in the pancreatic body, who underwent laparoscopic enucleation of the lesion with the aid of a hand-held gamma detecting probe.
Background & objectives: The prerequisite of radioimmunotherapy is stable binding of a radionucli... more Background & objectives: The prerequisite of radioimmunotherapy is stable binding of a radionuclide to monoclonal antibodies, which are specific to the tumour-associated antigen. Most B-cell lymphomas express CD20 antigen on the surface of the tumour cells, making it a suitable target for therapeutic radioactive monoclonal antibodies. In the present study, the immunoconjugate of biosimilar Rituximab (Reditux™) and macrocyclic chelator, p-SCN-Bz-DOTA, was prepared and radiolabelled with Lutetium-177 followed by quality control procedures. Methods: Rituximab(BioSim) was desalted with sodium bicarbonate (0.1M, pH 9.0) and incubated with DOTA-SCN (1:50). The effectiveness of the conjugation was evaluated by determining the number of chelators per antibody molecule. This conjugate was radiolabelled with Lutetium-177 and purified using PD10 column. The quality control parameters like pH, clarity, radiochemical purity, in vitro stability and sterility were studied. Immunoreactivity of 177 Lu-DOTA-Rituximab (BioSim) was assessed using RAMOS cells. The radioimmunoconjugate (RIC) after stringent quality assurance was injected in three patients and the biodistribution profile was analysed. Results: An average of 4.25 ± 1.04 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab (BioSim).The radiochemical purity of the labelled antibody was > 95 per cent with preserved affinity for CD20 antigen. The final preparation was stable up to about 120 h when tested under different conditions. A favourable biodistribution profile was observed with liver showing the maximum uptake of the RIC. Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim) in patients of relapsed and refractory non Hodgkin's lymphoma can be considered.
Given the high frequency of liver metastases in neuroendocrine tumor patients, we aimed to determ... more Given the high frequency of liver metastases in neuroendocrine tumor patients, we aimed to determine whether hepatic intraarterial administration of 90Y-DOTATOC peptide receptor radionuclide therapy (PRRT) would increase treatment efficacy while reducing systemic toxicity compared with systemic toxicity from intravenous administration as previously reported in the literature. Methods: PRRT-naïve adult neuroendocrine tumor patients with liver-dominant metastases were enrolled in a prospective single-center, open-label pilot study. The patients underwent baseline PET/CT using intravenous 68Ga-DOTATOC. Then, 3.5 ± 0.2 GBq (94.7 ± 5.4 mCi) of 90Y-DOTATOC were administered into the proper hepatic artery over 30 min. The first 5 patients also received intraarterial 68Ga-DOTATOC and underwent PET/CT. All patients were followed for response (RECIST, version 1.1) (primary aim 2, safety) and toxicity (Common Terminology Criteria for Adverse Events, version 4.0) (primary aim 1, efficacy) for at least 6 mo, with optional follow-up for up to 1 y. In the subset of 5 patients who underwent both intravenous and intraarterial 68Ga-DOTATOC PET/CT, tumor SUVmax was compared between intravenous and intraarterial administration for hepatic tumors, intrahepatic tumors, and uninvolved background organs (secondary aim, intravenous vs. intraarterial uptake). Results: The study was terminated after a planned analysis of the first 10 patients because of lack of efficacy. The best response was stable disease in 90% (9/10 patients) and progressive disease in 10% (1/10 patients) at 3 mo, and stable disease in 8 of 10 patients and progressive disease in 2 of 10 patients at 6 mo. One additional patient developed progressive disease after the 6-mo follow-up period but within the optional 1-y follow-up period. No partial response or complete response was observed. The 2 patients with the highest liver tumor burden died within 6 mo of treatment, with treatment considered a possible contributor. Patients who received intraarterial administration failed to demonstrate higher uptake by hepatic metastases than patients who received intravenous administration, with a median intraarterial-to-intravenous SUVmax ratio of 0.81 (range, 0.36–2.09) on a lesion level. Conclusion: Our study found that administration of PRRT via the proper hepatic artery did not reproduce the increase in hepatic tumor uptake that was previously reported. In addition, the single treatment using 90Y-DOTATOC did not induce tumor shrinkage, indicating that more treatment cycles may be required. Possible safety concerns in patients with a high liver tumor burden should inform patient selection for future studies.
Journal of cancer science and clinical therapeutics, 2019
Background: A sentinel lymph node (SLN) is considered to be the first lymph node which is drainin... more Background: A sentinel lymph node (SLN) is considered to be the first lymph node which is draining the tumor site. Radioactive Tc-99m labeled sulfur colloid, vital blue dye such as isosulfan blue or methylene blue, or the combination of the both is generally used for sentinel lymph node localization. In this study, we compare the sensitivity of both the methods to establish an effective method for SLN localization among early cases of breast cancer. Methods: Forty incidental cases, consulting the hospital between Jan 2015-June 2017 and diagnosed with early breast cancer (Stage T1N0M0 and T2N0M0) were subjected to sentinel lymph node detection by both radiocolloid and dye. 99m Tc-labeled are filtered sulfur colloid was administered intradermally in the periaerolar region in the tumor quadrant, 30 mins-1 h prior to the surgery. 1ml methylene blue dye, was administered, intraparenchymally, by circumareolar region during the surgery. All radioactive lymph nodes were removed until the background activity was less than one-tenth the ex-vivo value of hottest node. All the blue dye positive nodes, whether or not radiocolloid positive were excised and labeled accordingly and sent for histo-pathological examination.
225Ac-PSMA-617 therapy has shown good response in many recent studies. We report our experience o... more 225Ac-PSMA-617 therapy has shown good response in many recent studies. We report our experience of targeted alpha therapy with 225Ac-PSMA-617 in mCRPC patients who have failed therapy with taxanes. Thirty-eight patients with CRPC with progressive disease following at least one taxane-based chemotherapy received 225Ac-PSMA-617 between July 2017 and Nov 2019. Primary end point was a composite 50% PSA and radiological response. Secondary endpoints were PFS, OS, and changes in QOL. The differences in outcomes between patients with skeletal and lymph-node metastases versus those with visceral metastases were also studied. A composite response by predetermined criteria was observed in 25 (66%) of 38 patients. The median PFS was 8 months (95% CI 5.3–10.6 months). Median overall survival was 12 months (95% CI 9.1–14.9) with 16 patients alive at the time of censorship. There was no difference in response rates or survival statistics between patients with visceral metastases versus those with only bone and lymph-node metastases (Chi-square 1.51, df 1, Sig 0.218). The most common adverse effect was xerostomia. On the QOL Symptom score, Pain, Fatigue Insomnia, and constipation showed a significant improvement as compared to baseline. 225Ac-PSMA-617 is a safe and tolerable treatment option for mCRPC that demonstrates marked anti-tumour activity with improvement in quality of life even in patients of metastatic CRPC who have been previously treated with taxane-based chemotherapy.
This is an open access article distributed under the terms of the Creative Commons Attribution-No... more This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
Prostatic malignancy is the most common type of nonskin cancer and associated with significant mo... more Prostatic malignancy is the most common type of nonskin cancer and associated with significant morbidity and mortality. Early androgen deprivation therapy (ADT) is the treatment of choice in metastatic prostate cancer, whereas ADT delays progression of disease, but it is associated with significant adverse effects and frequently impairs the quality of life. Therefore, there is growing interest in treatments to postpone ADT while achieving a good progression-free survival. We present a case of oligometastatic prostate cancer, who was treated upfront with 177Lu-labeled PSMA radioligand therapy and demonstrated excellent response to a single dose of 177Lu-PSMA-617.
Dosimetric analysis of patients with gastro entero pancreatic neuroendocrine tumors (NETs) treate... more Dosimetric analysis of patients with gastro entero pancreatic neuroendocrine tumors (NETs) treated with PRCRT (peptide receptor chemo radionuclide therapy) using Lu-177 DOTATATE and capecitabine/ temozolomide (CAP/TEM).
OBJECTIVE The aim of the present study was to perform calculation of the absorbed doses to organs... more OBJECTIVE The aim of the present study was to perform calculation of the absorbed doses to organs at risk and to neuroendocrine tumors and to determine whether hepatic intra-arterial (IA) injection of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) would achieve higher intratumoral concentrations than standard intravenous administration of 177Lu-DOTATATE. METHODS 29 patients with Grade I-II, inoperable, metastatic gastro-entero-pancreatic neuroendocrine tumor (GEPNET) were prospectively identified and enrolled for the study. 15 patients of GEPNETs with liver-dominant metastatic disease and less than 3 sites of extrahepatic metastatic disease were administered a single dose of 177Lu-DOTATATE therapy through the selective catheterization of the hepatic artery (IA group). The other 14 patients received a single dose of 177 Lu- DOTATATE through standard intravenous route (IV group). For dosimetry, whole-body γ (anterior and posterior planar acquisitions) and SPECT/CT scans of the abdomen at 2, 24 and 96 h post 177Lu-DOTATATE administration were acquired. Dosimetric calculations were done using the HERMES software. RESULTS The mean dose per unit activity (DpA) in the liver and tumor lesions in the IA group differed significantly (p < 0.05) but differed insignificantly in spleen and kidneys (p > 05) with the IV group. The mean tumor/non-tumor concentration at 96 h was 76.83 ± 7.9 (range 10.2-251.3) in the IA group whereas it was 25.6 ± 5.9 (Range: 12-55) in the IV group. There was an average threefold increase in tumoral concentration over the standard intravenous group. CONCLUSION IA administration of 177Lu-DOTATATE results in higher concentration and absorbed dose in hepatic metastases in patients of GEPNETs as compared to a single dose of PRRT administered through standard IV route, and thus seems to be a powerful tool to improve the efficacy of PRRT. ADVANCES IN KNOWLEDGE Measurement of the dose received by the tumor lesions and the critical organs is of paramount importance for the prognostication of a radionuclide therapy. Scant data exist on the dosimetric impact of IA administration of the therapy with 177Lu-DOTATATE on the tumors and other organs, and this study would add an impact towards the better treatment outcome in patients of neuroendocrine tumor with liver-dominant metastatic disease.
Nuclear Medicine and Molecular Imaging, Sep 10, 2021
Laparoscopic resection of tumor is often performed for benign and small insulinomas, or for those... more Laparoscopic resection of tumor is often performed for benign and small insulinomas, or for those located in the body or tail of the pancreas. The precise preoperative and intraoperative localization of the insulinoma is critical to minimize the surgical intervention. Conventional imaging studies, i.e., MRI, CT, and endoscopic ultrasound have limited sensitivity due to the small size of the insulinomas. Angiography, intraarterial calcium stimulation, and venous sampling are invasive procedures with concomitant risk for complications. Exendin-4 PET/CT scan has shown to be of great value in preoperative localization of insulinomas. In the absence of the traditional gold standard, i.e., intraoperative ultrasound with manual palpation, in laparoscopic surgery, a simple enucleation procedure might not be possible. Gamma probe-assisted surgery is a new method of diagnosis and treatment which allows a small area of tissue to be identified and removed, while a large area of the organ or the system remains unaffected. We present a case of a 34-year-old man with clinical suspicion of insulinoma with negative conventional imaging and successful lesion localization with 68Ga-Exendin-4 PET/CT scan in the pancreatic body, who underwent laparoscopic enucleation of the lesion with the aid of a hand-held gamma detecting probe.
Background & objectives: The prerequisite of radioimmunotherapy is stable binding of a radionucli... more Background & objectives: The prerequisite of radioimmunotherapy is stable binding of a radionuclide to monoclonal antibodies, which are specific to the tumour-associated antigen. Most B-cell lymphomas express CD20 antigen on the surface of the tumour cells, making it a suitable target for therapeutic radioactive monoclonal antibodies. In the present study, the immunoconjugate of biosimilar Rituximab (Reditux™) and macrocyclic chelator, p-SCN-Bz-DOTA, was prepared and radiolabelled with Lutetium-177 followed by quality control procedures. Methods: Rituximab(BioSim) was desalted with sodium bicarbonate (0.1M, pH 9.0) and incubated with DOTA-SCN (1:50). The effectiveness of the conjugation was evaluated by determining the number of chelators per antibody molecule. This conjugate was radiolabelled with Lutetium-177 and purified using PD10 column. The quality control parameters like pH, clarity, radiochemical purity, in vitro stability and sterility were studied. Immunoreactivity of 177 Lu-DOTA-Rituximab (BioSim) was assessed using RAMOS cells. The radioimmunoconjugate (RIC) after stringent quality assurance was injected in three patients and the biodistribution profile was analysed. Results: An average of 4.25 ± 1.04 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab (BioSim).The radiochemical purity of the labelled antibody was > 95 per cent with preserved affinity for CD20 antigen. The final preparation was stable up to about 120 h when tested under different conditions. A favourable biodistribution profile was observed with liver showing the maximum uptake of the RIC. Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim) in patients of relapsed and refractory non Hodgkin's lymphoma can be considered.
Given the high frequency of liver metastases in neuroendocrine tumor patients, we aimed to determ... more Given the high frequency of liver metastases in neuroendocrine tumor patients, we aimed to determine whether hepatic intraarterial administration of 90Y-DOTATOC peptide receptor radionuclide therapy (PRRT) would increase treatment efficacy while reducing systemic toxicity compared with systemic toxicity from intravenous administration as previously reported in the literature. Methods: PRRT-naïve adult neuroendocrine tumor patients with liver-dominant metastases were enrolled in a prospective single-center, open-label pilot study. The patients underwent baseline PET/CT using intravenous 68Ga-DOTATOC. Then, 3.5 ± 0.2 GBq (94.7 ± 5.4 mCi) of 90Y-DOTATOC were administered into the proper hepatic artery over 30 min. The first 5 patients also received intraarterial 68Ga-DOTATOC and underwent PET/CT. All patients were followed for response (RECIST, version 1.1) (primary aim 2, safety) and toxicity (Common Terminology Criteria for Adverse Events, version 4.0) (primary aim 1, efficacy) for at least 6 mo, with optional follow-up for up to 1 y. In the subset of 5 patients who underwent both intravenous and intraarterial 68Ga-DOTATOC PET/CT, tumor SUVmax was compared between intravenous and intraarterial administration for hepatic tumors, intrahepatic tumors, and uninvolved background organs (secondary aim, intravenous vs. intraarterial uptake). Results: The study was terminated after a planned analysis of the first 10 patients because of lack of efficacy. The best response was stable disease in 90% (9/10 patients) and progressive disease in 10% (1/10 patients) at 3 mo, and stable disease in 8 of 10 patients and progressive disease in 2 of 10 patients at 6 mo. One additional patient developed progressive disease after the 6-mo follow-up period but within the optional 1-y follow-up period. No partial response or complete response was observed. The 2 patients with the highest liver tumor burden died within 6 mo of treatment, with treatment considered a possible contributor. Patients who received intraarterial administration failed to demonstrate higher uptake by hepatic metastases than patients who received intravenous administration, with a median intraarterial-to-intravenous SUVmax ratio of 0.81 (range, 0.36–2.09) on a lesion level. Conclusion: Our study found that administration of PRRT via the proper hepatic artery did not reproduce the increase in hepatic tumor uptake that was previously reported. In addition, the single treatment using 90Y-DOTATOC did not induce tumor shrinkage, indicating that more treatment cycles may be required. Possible safety concerns in patients with a high liver tumor burden should inform patient selection for future studies.
Journal of cancer science and clinical therapeutics, 2019
Background: A sentinel lymph node (SLN) is considered to be the first lymph node which is drainin... more Background: A sentinel lymph node (SLN) is considered to be the first lymph node which is draining the tumor site. Radioactive Tc-99m labeled sulfur colloid, vital blue dye such as isosulfan blue or methylene blue, or the combination of the both is generally used for sentinel lymph node localization. In this study, we compare the sensitivity of both the methods to establish an effective method for SLN localization among early cases of breast cancer. Methods: Forty incidental cases, consulting the hospital between Jan 2015-June 2017 and diagnosed with early breast cancer (Stage T1N0M0 and T2N0M0) were subjected to sentinel lymph node detection by both radiocolloid and dye. 99m Tc-labeled are filtered sulfur colloid was administered intradermally in the periaerolar region in the tumor quadrant, 30 mins-1 h prior to the surgery. 1ml methylene blue dye, was administered, intraparenchymally, by circumareolar region during the surgery. All radioactive lymph nodes were removed until the background activity was less than one-tenth the ex-vivo value of hottest node. All the blue dye positive nodes, whether or not radiocolloid positive were excised and labeled accordingly and sent for histo-pathological examination.
225Ac-PSMA-617 therapy has shown good response in many recent studies. We report our experience o... more 225Ac-PSMA-617 therapy has shown good response in many recent studies. We report our experience of targeted alpha therapy with 225Ac-PSMA-617 in mCRPC patients who have failed therapy with taxanes. Thirty-eight patients with CRPC with progressive disease following at least one taxane-based chemotherapy received 225Ac-PSMA-617 between July 2017 and Nov 2019. Primary end point was a composite 50% PSA and radiological response. Secondary endpoints were PFS, OS, and changes in QOL. The differences in outcomes between patients with skeletal and lymph-node metastases versus those with visceral metastases were also studied. A composite response by predetermined criteria was observed in 25 (66%) of 38 patients. The median PFS was 8 months (95% CI 5.3–10.6 months). Median overall survival was 12 months (95% CI 9.1–14.9) with 16 patients alive at the time of censorship. There was no difference in response rates or survival statistics between patients with visceral metastases versus those with only bone and lymph-node metastases (Chi-square 1.51, df 1, Sig 0.218). The most common adverse effect was xerostomia. On the QOL Symptom score, Pain, Fatigue Insomnia, and constipation showed a significant improvement as compared to baseline. 225Ac-PSMA-617 is a safe and tolerable treatment option for mCRPC that demonstrates marked anti-tumour activity with improvement in quality of life even in patients of metastatic CRPC who have been previously treated with taxane-based chemotherapy.
This is an open access article distributed under the terms of the Creative Commons Attribution-No... more This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
Prostatic malignancy is the most common type of nonskin cancer and associated with significant mo... more Prostatic malignancy is the most common type of nonskin cancer and associated with significant morbidity and mortality. Early androgen deprivation therapy (ADT) is the treatment of choice in metastatic prostate cancer, whereas ADT delays progression of disease, but it is associated with significant adverse effects and frequently impairs the quality of life. Therefore, there is growing interest in treatments to postpone ADT while achieving a good progression-free survival. We present a case of oligometastatic prostate cancer, who was treated upfront with 177Lu-labeled PSMA radioligand therapy and demonstrated excellent response to a single dose of 177Lu-PSMA-617.
Dosimetric analysis of patients with gastro entero pancreatic neuroendocrine tumors (NETs) treate... more Dosimetric analysis of patients with gastro entero pancreatic neuroendocrine tumors (NETs) treated with PRCRT (peptide receptor chemo radionuclide therapy) using Lu-177 DOTATATE and capecitabine/ temozolomide (CAP/TEM).
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