Biokinetics and dosimetry in patients administered with 111In-DOTA-Tyr3-octreotide: implications for internal radiotherapy with 90Y-DOTATOC

Recent advances in receptor-mediated tumour imaging have resulted in the development of a new somatostatin analogue, DOTA-dPhe¹-Tyr³-octreotide. This new compound, named DOTATOC, has shown high affinity for somatostatin receptors, ease of labelling and stability with yttrium-90 and favourable biodistribution in animal models. The aim of this work was to evaluate the biodistribution and dosimetry of DOTATOC radiolabelled with indium-111, in anticipation of therapy trials with ⁹⁰Y-DOTATOC in patients. Eighteen patients were injected with DOTATOC (10 μg), labelled with 150–185 MBq of ¹¹¹In. Blood and urine samples were collected throughout the duration of the study (0–2 days). Planar and single-photon emission tomography images were acquired at 0.5, 3–4, 24 and 48 h and time-activity curves were obtained for organs and tumours. A compartmental model was used to determine the kinetic parameters for each organ. Dose calculations were performed according to the MIRD formalism. Specific activities of >37 GBq/ μmol were routinely achieved. Patients showed no acute or delayed adverse reactions. The residence time for ¹¹¹In-DOTATOC in blood was 0.9±0.4 h. The injected activity excreted in the urine in the first 24 h was 73%±11%. The agent localized primarily in spleen, kidneys and liver. The residence times in source organs were: 2.2±1.8 h in spleen, 1.7±1.2 h in kidneys, 2.4±1.9 h in liver, 1.5±0.3 h in urinary bladder and 9.4±5.5 h in the remainder of the body; the mean residence time in tumour was 0.47 h (range: 0.03–6.50 h). Based on our findings, the predicted absorbed doses for ⁹⁰Y-DOTATOC would be 7.6±6.3 (spleen), 3.3±2.2 (kidneys), 0.7±0.6 (liver), 2.2±0.3 (bladder), 0.03±0.01 (red marrow) and 10.1 (range: 1.4–31.0) (tumour) mGy/MBq. These results indicate that high activities of ⁹⁰Y-DOTATOC can be administered with low risk of myelotoxicity, although with potentially high radiation doses to the spleen and kidneys. Tumour doses were high enough in most cases to make it likely that the disired therapeutic response desired would be obtained. Received 17 February and in revised form 22 April 1999     

^111In—DTPA—octreotide在生长抑素受体表达阳性肿瘤的初步临床应用

目的评价自制111In-DTPA-octreotide在生长抑素受体表达阳性肿瘤显像中的应用价值.材料和方法36例患者行111In-DTPA-octreotide显像.包括神经内分泌性肿瘤15例,非神经内分泌性肿瘤14例以及7例肺部良性病变.静注111In-DTPA-octreotide 185Mq后于4、24h行局部及全身显像,部分病例行断层显像.结果13例神经内分泌肿瘤、12例非神经内分泌性肿瘤和3例肺部良性病变显像阳性.2例神经内分泌肿瘤、2例非神经内分泌性肿瘤和4例肺部良性病变显像阴性.肺癌患者显像均为阳性.本研究灵敏度86.2%,特异性57.1%,准确性80.6%.结论111In-DTPA-octreotide对生长抑素受体表达阳性肿瘤肿瘤显像均有较高的诊断价值,但肺部良恶性病变的特异性不高.     

Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumours: comparison of 86Y-DOTATOC and 111In-DTPA-octreotide

The somatostatin analogue ⁹⁰Y-DOTATOC (yttrium-90 DOTA-D-Phe¹-Tyr³-octreotide) is used for treatment of patients with neuroendocrine tumours. Accurate pretherapeutic dosimetry would allow for individual planning of the optimal therapeutic strategy. In this study, the biodistribution and resulting dosimetric calculation for therapeutic exposure of critical organs and tumour masses based on the positron emission tomography (PET) tracer ⁸⁶Y-DOTATOC, which is chemically identical to the therapeutic agent, were compared with results based on the tracer commonly used for somatostatin receptor scintigraphy, ¹¹¹In-DTPA-octreotide (indium-111 DTPA-D-Phe¹-octreotide, OctreoScan). Three patients with metastatic carcinoid tumours were investigated. Dynamic and static PET studies with 77-186 MBq ⁸⁶Y-DOTATOC were performed up to 48 h after injection. Serum and urinary activity were measured simultaneously. Within 1 week, but not sooner than 5 days, patients were re-investigated by conventional scintigraphy with ¹¹¹In-DTPA-octreotide (110-187 MBq) using an equivalent protocol. Based on the regional tissue uptake kinetics, residence times were calculated and doses for potential therapy with ⁹⁰Y-DOTATOC were estimated. Serum kinetics and urinary excretion of both tracers showed no relevant differences. Estimated liver doses were similar for both tracers. Dose estimation for organs with the highest level of radiation exposure, the kidneys and spleen, showed differences of 10.5%-20.1% depending on the tracer. The largest discrepancies in dose estimation, ranging from 23.1% to 85.9%, were found in tumour masses. Furthermore, there was a wide inter-subject variability in the organ kinetics. Residence times (F_organs) for ⁹⁰Y-DOTATOC therapy were: F_liver 1.59-2.79 h; F_spleen 0.07-1.68 h; and F_kidneys 0.55-2.46 h (based on ⁸⁶Y-DOTATOC). These data suggest that dosimetry based on ⁸⁶Y-DOTATOC and ¹¹¹In-DTPA-octreotide yields similar organ doses, whereas there are relevant differences in estimated tumour doses. Individual pretherapeutic dosimetry for ⁹⁰Y-DOTATOC therapy appears necessary considering the large differences in organ doses between individual patients. If possible, the dosimetry should be performed with the chemically identical tracer ⁸⁶Y-DOTATOC.     

Biokinetics and dosimetry in patients administered with (111)In-DOTA-Tyr(3)-octreotide: implications for internal radiotherapy with (90)Y-DOTATOC.

Recent advances in receptor-mediated tumour imaging have resulted in the development of a new somatostatin analogue, DOTA-dPhe(1)-Tyr(3)-octreotide. This new compound, named DOTATOC, has shown high affinity for somatostatin receptors, ease of labelling and stability with yttrium-90 and favourable biodistribution in animal models. The aim of this work was to evaluate the biodistribution and dosimetry of DOTATOC radiolabelled with indium-111, in anticipation of therapy trials with (90)Y-DOTATOC in patients. Eighteen patients were injected with DOTATOC (10 microg), labelled with 150-185 MBq of (111)In. Blood and urine samples were collected throughout the duration of the study (0-2 days). Planar and single-photon emission tomography images were acquired at 0.5, 3-4, 24 and 48 h and time-activity curves were obtained for organs and tumours. A compartmental model was used to determine the kinetic parameters for each organ. Dose calculations were performed according to the MIRD formalism. Specific activities of >37 GBq/ micromol were routinely achieved. Patients showed no acute or delayed adverse reactions. The residence time for (111)In-DOTATOC in blood was 0.9+/-0.4 h. The injected activity excreted in the urine in the first 24 h was 73%+/-11%. The agent localized primarily in spleen, kidneys and liver. The residence times in source organs were: 2.2+/-1.8 h in spleen, 1.7+/-1.2 h in kidneys, 2.4+/-1.9 h in liver, 1.5+/-0.3 h in urinary bladder and 9. 4+/-5.5 h in the remainder of the body; the mean residence time in tumour was 0.47 h (range: 0.03-6.50 h). Based on our findings, the predicted absorbed doses for (90)Y-DOTATOC would be 7.6+/-6.3 (spleen), 3.3+/-2.2 (kidneys), 0.7+/-0.6 (liver), 2.2+/-0.3 (bladder), 0.03+/-0.01 (red marrow) and 10.1 (range: 1.4-31.0) (tumour) mGy/MBq. These results indicate that high activities of (90)Y-DOTATOC can be administered with low risk of myelotoxicity, although with potentially high radiation doses to the spleen and kidneys. Tumour doses were high enough in most cases to make it likely that the desired therapeutic response desired would be obtained.     

Biokinetics and dosimetry for 195Au,evaluated in an animal model

The use of the generator produced radionuclide ^195mAu, half life 30 s, has become feasible for several different investigations, e.g. cardiac studies. To assess the absorbed dose from the long lived radionuclide ¹⁹⁵Au (the daughter of ^195mAu, half life 183 days), a biodistribution study of ¹⁹⁵Au was performed in animals. Seven rabbits were injected with eluate from a ^195mHg-^195mAu generator and the retention and the biodistribution of the long lived gold isotope was investigated. The activity was localized mainly in the liver and the kidneys. Transforming the data to man resulted in an absorbed dose from ¹⁹⁵Au from 1 elution (approximately 925 MBq ^195mAu) of 2.2 mGy to the kidney and 1.3 mGy to the liver and an effective dose equivalent of 0.26 mSv. The total effective dose equivalent from all radionuclides in the eluate (^195mAu, ¹⁹⁵Au, ^195mHg and ¹⁹⁵Hg), was estimated to be 0.65 mSv for a single injection (925 MBq ^195mAu).     

Biokinetics and dosimetry for 195Au, evaluated in an animal model

The use of the generator produced radionuclide 195mAu, half life 30 s, has become feasible for several different investigations, e.g. cardiac studies. To assess the absorbed dose from the long lived radionuclide 195Au (the daughter of 195mAu, half life 183 days), a biodistribution study of 195Au was performed in animals. Seven rabbits were injected with eluate from a 195mHg-195mAu generator and the retention and the biodistribution of the long lived gold isotope was investigated. The activity was localized mainly in the liver and the kidneys. Transforming the data to man resulted in an absorbed dose from 195Au from 1 elution (approximately 925 MBq 195mAu) of 2.2 mGy to the kidney and 1.3 mGy to the liver and an effective dose equivalent of 0.26 mSv. The total effective dose equivalent from all radionuclides in the eluate (195mAu, 195Au, 195mHg and 195Hg), was estimated to be 0.65 mSv for a single injection (925 MBq 195mAu).     

Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumours: comparison of (86)Y-DOTATOC and (111)In-DTPA-octreotide.

The somatostatin analogue (90)Y-DOTATOC (yttrium-90 DOTA- D-Phe(1)-Tyr(3)-octreotide) is used for treatment of patients with neuroendocrine tumours. Accurate pretherapeutic dosimetry would allow for individual planning of the optimal therapeutic strategy. In this study, the biodistribution and resulting dosimetric calculation for therapeutic exposure of critical organs and tumour masses based on the positron emission tomography (PET) tracer (86)Y-DOTATOC, which is chemically identical to the therapeutic agent, were compared with results based on the tracer commonly used for somatostatin receptor scintigraphy, (111)In-DTPA-octreotide (indium-111 DTPA- D-Phe(1)-octreotide, OctreoScan). Three patients with metastatic carcinoid tumours were investigated. Dynamic and static PET studies with 77-186 MBq (86)Y-DOTATOC were performed up to 48 h after injection. Serum and urinary activity were measured simultaneously. Within 1 week, but not sooner than 5 days, patients were re-investigated by conventional scintigraphy with (111)In-DTPA-octreotide (110-187 MBq) using an equivalent protocol. Based on the regional tissue uptake kinetics, residence times were calculated and doses for potential therapy with (90)Y-DOTATOC were estimated. Serum kinetics and urinary excretion of both tracers showed no relevant differences. Estimated liver doses were similar for both tracers. Dose estimation for organs with the highest level of radiation exposure, the kidneys and spleen, showed differences of 10.5%-20.1% depending on the tracer. The largest discrepancies in dose estimation, ranging from 23.1% to 85.9%, were found in tumour masses. Furthermore, there was a wide inter-subject variability in the organ kinetics. Residence times (tau(organs)) for (90)Y-DOTATOC therapy were: tau(liver) 1.59-2.79 h; tau(spleen) 0.07-1.68 h; and tau(kidneys) 0.55-2.46 h (based on (86)Y-DOTATOC). These data suggest that dosimetry based on (86)Y-DOTATOC and (111)In-DTPA-octreotide yields similar organ doses, whereas there are relevant differences in estimated tumour doses. Individual pretherapeutic dosimetry for (90)Y-DOTATOC therapy appears necessary considering the large differences in organ doses between individual patients. If possible, the dosimetry should be performed with the chemically identical tracer (86)Y-DOTATOC.     

Megalin is essential for renal proximal tubule reabsorption of (111)In-DTPA-octreotide.

Radiolabeled somatostatin analogs have been shown to be important radiopharmaceuticals for tumor diagnosis and radionuclide therapy. The kidney has appeared to be the critical organ during radionuclide therapy because of peptide reabsorption and retention in the proximal tubules after glomerular filtration. The molecular mechanism of renal reabsorption of these analogs has not been clarified. A possible receptor candidate is megalin, a multiligand scavenger receptor in the renal proximal tubules. The objective of this study was to investigate the role of megalin in tubular reabsorption of radiolabeled somatostatin analogs by using kidney-specific megalin-deficient mice versus mice with normal renal megalin expression. [(111)In-Diethylenetriaminepentaacetic acid (DTPA)]octreotide was used as a practical model of peptide. METHODS: Renal uptake of [(111)In-DTPA]octreotide was determined by animal SPECT scintigraphy at different time points after injection of the tracer and by measurement of radioactivity after isolation of the organs. Furthermore, ex vivo autoradiography of renal sections revealed the zonal distribution of radioactivity in the megalin-deficient and megalin-expressing kidneys. RESULTS: SPECT scintigraphy of [(111)In-DTPA]octreotide at 3 and 24 h after injection clearly showed lower renal radioactivity in megalin-deficient kidneys than in megalin-expressing kidneys, both in male and in female mice, in accordance with counts obtained after isolation of the organ (70%-85% reduction of uptake in the megalin-deficient kidneys, P < 0.001). Renal uptake of [(111)In-DTPA]octreotide was significantly higher in female than in male kidneys (P < 0.001). Ex vivo autoradiograms clearly showed that renal radioactivity was not homogeneously distributed in the megalin-expressing kidneys but localized in the renal cortex. Quantification of the autoradiogram data confirmed the reduced radioactivity in the renal cortex of megalin-deficient kidneys. CONCLUSION: This study revealed the molecular mechanism of [(111)In-DTPA]octreotide uptake in renal proximal tubules involving the receptor megalin. Identification of megalin may be crucial for further research into strategies to reduce renal uptake.     

An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors.

The aim of this study was to compare the imaging abilities of the recently developed somatostatin analog, (99m)Tc-hydrazinonicotinyl-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC [(99m)Tc-TOC]), with (111)In-diethylenediaminepentaacetic acid-D-Phe(1)-octreotide ((111)In-OCT [Octreoscan]) in patients undergoing routine somatostatin receptor (SSTR) scintigraphy. METHODS: Forty-one patients (20 men, 21 women; age range, 29-75 y; mean age, 56.7 y) with either histologically proven or biologically and clinically suspected endocrine tumors were enrolled in the study. Four groups were distinguished: (a) patients being evaluated for the detection and localization of neuroendocrine tumors (n = 6), (b) tumor staging (n = 19), (c) patients being investigated to determine the SSTR status of tumor lesions (n = 11), and (d) patient follow-up studies (n = 5). Each patient received a mean activity of 150 MBq (111)In-OCT and 350-400 MBq (99m)Tc-TOC. Scintigraphy with (99m)Tc-TOC was performed 4 h after injection and scintigraphy with (111)In-OCT was performed 4 and 24 h after injection. SPECT studies of areas of interest were performed 4 h after injection for both tracers as well as at 24 h after injection for (111)In-OCT. The time interval between the studies using each tracer ranged from 2 to 22 d (mean interval, 9.3 d). RESULTS: (111)In-OCT and (99m)Tc-TOC showed an equivalent scan result in 32 patients (78%), 9 cases showed discrepancies (22%), false-negative results with (111)In-OCT were seen in 6 cases (14.6%), whereas (99m)Tc-TOC was false-positive in 2 cases (4.9%). (111)In-OCT was true-negative in both cases. The false-positive findings of the (99m)Tc-TOC studies were caused by nonspecific uptake in the bowel. In 1 case, (99m)Tc-TOC correctly identified a metastasis in the lumbar spine but both scan results were false-positive because of an inflammatory process. In 21 patients with SSTR-expressing tumors, the semiquantitative region-of-interest analysis showed that (99m)Tc-TOC achieved higher tumor-to-normal tissue ratios than (111)In-OCT. CONCLUSION: This study revealed a higher sensitivity of (99m)Tc-TOC as compared with (111)In-OCT as an imaging agent for the localization of SSTR-expressing tumors. To avoid false-positive findings with (99m)Tc-OCT due to nonspecific tracer accumulation, additional scanning at 1-2 h after injection should be done.     

Biokinetics of 111In-DTPA-D-Phe(1)-octreotide in nude mice transplanted with a human carcinoid tumor

The long time biokinetics of the radiolabeled somatostatin analogues 111In-DTPA-D-Phe(1)-octreotide was studied in nude mice transplanted with the human carcinoid tumor, GOT1. The results were compared with those from the patient with the original tumor. This patient has been diagnosed and later treated with 111In-DTPA-D-Phe(1)-octreotide. The animals received about 2 MBq 111In-DTPA-D-Phe(1)-octreotide (0.1 microg) by injection into a tail vein. The animals were killed 0.5 h-14 d after injection of the radiopharmaceutical. Tumor tissue and normal tissues were collected and weighed and measured for 111In activity. The 111In uptake in the tumor was higher than in all normal tissues except the kidneys. The tumor-to-normal-tissue activity concentration, TNC, increased with time for all normal tissues studied. These data were similar to those observed for the original tumor in the patient. The similar biokinetics for 111In-DTPA-D-Phe(1)-octreotide in the tumor-bearing mice and the patient makes this animal model suitable as a model for evaluation of therapy of somatostatin receptor (sstr) expressing tumors with radiolabeled somatostatin analogues. Furthermore, the increase with time of TNC both in mice and the patient indicates that long-lived radionuclides are preferred for therapy with radiolabeled somatostatin analogues.     

Impact of 111In-DTPA-octreotide SPECT/CT fusion images in the management of neuroendocrine tumours

Purpose  Somatostatin receptor scintigraphy with [¹¹¹In]-diethylene triamine pentaacetate acid (DTPA)-octreotide is an accurate method for detecting neuroendocrine tumours (NETs) but often does not provide clear anatomical localisation of lesions. The aim of this study was to assess the clinical usefulness of anatomical-functional image fusion. Materials and methods  Fifty-four patients with known or suspected NET were included in the study. Planar and single-photon-emission computed tomography (SPECT) imaging was performed using a dual-head gamma camera equipped with an integrated X-ray transmission system, and the images were first interpreted alone by two nuclear medicine physicians and then compared with SPECT/CT fusion images together with a radiologist. The improvement provided by SPECT/CT in the interpretation of SPECT data alone and any modification in patientmanagement were recorded. Results  Fusion images improved SPECT interpretation in 23 cases, providing precise anatomical localisation of increased tracer uptake in 20 cases and disease exclusion in sites of physiological uptake in 5. In 10 patients, SPECT/CT allowed definition of the functional significance of lesions detected by diagnostic CT. SPECT/CT data modified clinical management in 14 cases by changing the diagnostic approach in 8 and the therapeutic modality in 6. Conclusions  Our study demonstrates that image fusion is clearly superior to SPECT alone, allowing precise localisation of lesions and reducing false-positive results.      

Six month follow-up after 111In-DTPA-octreotide therapy in patients with progressive radioiodine non-responsive thyroid cancer: a pilot study

BACKGROUND AND AIM: 111In-DTPA-octreotide is internalized by thyroid and neuroendocrine cancer cells via somatostatin receptor subtypes and can cause DNA damage by the emission of conversion and Auger electrons. The aim of the study was to determine the effect of 111In-DTPA-octreotide therapy in patients with progressive radioiodine non-responsive thyroid cancer in relation to 111In-DTPA-octreotide uptake by tumour localizations assessed on pre-treatment diagnostic octreotide scans. METHODS: Eleven consecutive patients, selected on positive pretreatment diagnostic scans, were treated with fixed doses of approx. 7400 MBq of 111In-DTPA-octreotide with an interval of 2-3 weeks between the doses. In one patient, the dose was adjusted because of sickle-cell disease. To assess the effects during treatment with 111In-DTPA-octreotide thyroglobulin levels were gathered from 2 years before treatment, during treatment and up to 1 year after treatment. A computed tomography scan was performed 3 months after the last treatment. RESULTS: Two patients died during and shortly after the treatment course. Death was due to a sepsis and an insulin overdose, respectively. In 44% of the patients, stable disease was achieved up to 6 months after the first treatment according to both criteria. All four had relative low pretreatment thyroglobulin values (mean value 275 microg.l), representing limited metastasized disease. In two patients biochemical stable disease was observed, whereas computed tomography showed tumour progression. CONCLUSION: Treatment with high doses of 111In-DTPA-octreotide in differentiated thyroid cancer results in a stable disease in a subgroup of patients. Our results suggest that a low pre-treatment thyroglobulin value, representing a small tumour load, may be a selection criterion for treatment.     

Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake.

Scintigraphy with [111In-diethylenetriamine pentaacetic acid0-D-Phe1]-octreotide (DTPAOC) is used to demonstrate neuroendocrine and other somatostatin-receptor-positive tumors. Despite encouraging results, this 111In-labeled compound is not well suited for peptide-receptor-mediated radiotherapy of somatostatin-receptor-positive tumors. Another somatostatin analog, [1,4,7,10-tetraazacyclododecane-N,N',N",N'-tetraacetic acid0, D-Phe1, Tyr3]-octreotide (DOTATOC), can be labeled with the beta-emitter 90Y in a stable manner. METHODS: We compared the distribution, kinetics and dosimetry of 111In-DTPAOC and 111In-DOTATOC in eight patients to predict the outcomes of these parameters in patients who will be treated with 90Y-DOTATOC. RESULTS: Serum radioactivity levels for the radiopharmaceuticals did not differ significantly 2-24 h after injection (P>0.05). Up to 2 h postinjection they were slightly, but significantly, lower after administration of 111In-DOTATOC (P < 0.01 at most time points). The percentage of peptide-bound radioactivity in serum did not differ after administration of either compound. Urinary excretion was significantly lower after administration of 111In-DOTATOC (P < 0.01). The visualization of known somatostatin-receptor-positive organs and tumors was clearer after administration of 111In-DOTATOC than after administration of 111In-DTPAOC. This was confirmed by significantly higher calculated uptakes in the pituitary gland and spleen. The uptake in the tumor sites did not differ significantly (P > 0.05), although in three of the four patients in whom tumor uptake could be calculated, it was higher after administration of 111In-DOTATOC. CONCLUSION: The distribution and excretion pattern of 111In-DOTATOC resembles that of 111In-DTPAOC, and the uptake in somatostatin-receptor-positive organs and most tumors is higher for 111In-DOTATOC. If 90Y-DOTATOC shows an uptake pattern similar to 111In-DOTATOC, it is a promising radiopharmaceutical for peptide-receptor-mediated radiotherapy in patients with somatostatin-receptor-positive tumors.     

Comparison of 111In-DOTA-DPhe1-Tyr3-octreotide and 111In-DOTA-lanreotide scintigraphy and dosimetry in patients with neuroendocrine tumours

Purpose Somatostatin receptor scintigraphy with ¹¹¹In-DOTA-DPhe¹-Tyr³-octreotide (¹¹¹In-DOTA-TOC) and ¹¹¹In-DOTA-lanreotide (¹¹¹In-DOTA-LAN) has been used for staging of neuroendocrine tumours (NETs). However, the comparative diagnostic value of these radioligands on a lesion basis has not yet been established. The aim of this study was to compare the diagnostic capacity of ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy in patients with NETs, evaluating whether significant differences exist in lesion imaging with these radioligands. Furthermore, dosimetric data were compared. Methods Forty-five patients with NETs were investigated with ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy. Scintigraphic results were compared with those of conventional imaging and/or surgery in each patient, and also ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in 20 patients. Results ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN scintigraphy were true positive in 42/45 (93%) and 39/45 (87%) patients, and imaged 74/91 (81%) and 73/91 (80%) tumour lesions, respectively. ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN detected liver metastases in 21 and 14 patients, mediastinal metastases in seven and 11 patients, and bone metastases in two and seven patients, respectively. These radioligands revealed lesions not seen by conventional imaging in seven and eight patients, respectively, or by ¹⁸F-FDG-PET in eight and seven patients, respectively. The estimated tumour absorbed doses for ⁹⁰Y-DOTA-TOC were higher than those for ⁹⁰Y-DOTA-LAN in 14 patients, whereas the opposite was true in 12 patients. Conclusion Both ¹¹¹In-DOTA-TOC and ¹¹¹In-DOTA-LAN are suitable for imaging tumour lesions in patients with NETs and can detect lesions that may not be seen by conventional imaging and ¹⁸F-FDG-PET. Compared with ¹¹¹In-DOTA-LAN, ¹¹¹In-DOTA-TOC has a superior diagnostic capacity for liver metastases, but a lower diagnostic capacity for metastatic lesions in mediastinum and bone.     

Body surface dosimetry following re-injection of 111In-leucocytes

The dose to a young infant cared for by a parent re-injected with 111In-leucocytes was estimated from the exposure of thermoluminescent dosimeters at five sites on the chest wall of eight patients. The UK Guidance Notes recommend that patients with a residual activity exceeding 20 MBq of 111In should avoid non-essential contact with children. The results confirmed those of an earlier preliminary study which showed that re-injection of 20 MBq of 111In-leucocytes to a parent could lead to a close contact dose greater than 1 mSv. It was concluded that the 111In-leucocyte activity administered to a parent of a young infant should not exceed 10 MBq.     

In-111-labeled liposomes: dosimetry and tumor depiction

Neutral phospholipid vesicles (liposomes) were loaded with 0.5 mCi (18.5 MBq) indium-111 and administered to 24 patients with various types of cancer. The median diameter of the liposomes was 77 nm, and lipid dose was 0.78-6.25 mg/kg. Scans obtained 24 and 48 hours after injection of In-111 liposomes showed gradual blood clearance with homogeneous uptake in the normal liver and spleen. Dosimetric estimates for these organs were 2.3 +/- 1.1 and 2.3 +/- 1.4 rad (.02 +/- .01 Gy), respectively, with a whole-body estimate of 0.28 rad (.003 Gy). Radiation dose did not correlate with lipid dose. Total renal excretion of In-111 was less than 2% of the injected dose in all but two patients. Transient eosinophilia occurred in two patients. Tumor was seen in the scans of 22 of 24 patients (unbinded readings). In-111-labeled liposomes may enable the demonstration of suspected or unsuspected sites of tumor.     

Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours

Purpose  

Although somatostatin receptor positron emission tomography (PET)/CT is gaining increasing popularity and has shown its diagnostic superiority in several studies, ¹¹¹In-diethylenetriaminepentaacetic acid (DTPA)-octreotide is still the current standard for diagnosis of neuroendocrine tumours (NET). The aim of this study was to compare the costs for the two diagnostic tests and the respective consequential costs.     

The distribution and dosimetry of 111-IN-bleomycin in man.

The distribution of 111-In in the human body was studied after the injection of -111-In-bleomycin for tumour localization. Uptake in body organs was measured by quantitative scanning using a dual detector scanner. The estimated absorbed dose from an injection of 1 mCi was 0.3 rad to the whole body, and approximately 1 rad to bone marrow, kidneys, liver and spleen.     

Biokinetics and dosimetry in patients of 99mTc-EDDA/HYNIC-Tyr3-octreotide prepared from lyophilized kits.

99mTc-EDDA/HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. The aim of this study was to establish a biokinetic model for 99mTc-HYNIC-TOC prepared from lyophilized kits, and to evaluate its dosimetry as a tumor imaging agent in patients with histologically confirmed neuroendocrine tumors. Whole-body images from eight patients were acquired at 5, 60, 90, 180 min and 24 h after 99mTc-HYNIC-TOC administration obtained from instant freeze-dried kit formulations with radiochemical purities >95%. Regions of interest (ROIs) were drawn around source organs on each time frame. The same set of ROIs was used for all eight scans and the count per minute (cpm) of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate 99mTc-HYNIC-TOC time-activity curves in each organ, to adjust a biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. Images showed an average tumor/blood (heart) ratio of 4.3+/-0.7 in receptor-positive tumors at 1 h. The mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv.