Kooij, P.P.M.

Bone marrow dosimetry in peptide receptor radionuclide therapy with [ 177Lu-DOTA0,Tyr3]octreotate (Article)

2009-07-01T00:00:00Z

Purpose: Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called "remainder of the body" to the bone marrow. Methods: Bone marrow aspirates were drawn in 15 patients after treatment with [177Lu-DOTA0,Tyr3]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment. Results: A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (r=0.914, p<0.001). No correlation between the calculated absorbed dose in the bone marrow and the change in platelets was found. There was a considerable contribution from other organs and the remainder of the body to the bone marrow absorbed dose. Conclusion: (1) After PRRT with [177Lu-DOTA0,Tyr3]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone marrow dose is significant; and (4) There is considerable variation in bone marrow absorbed dose between patients. These findings imply that for individual dose optimization, individual calculation of the bone marrow absorbed dose is necessary.

Comparison of three radiolabelled peptide analogues for CCK-2 receptor scintigraphy in medullary thyroid carcinoma (Article)

2009-03-06T00:00:00Z

Purpose: Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in a high percentage of medullary thyroid carcinomas (MTC). Analogous to somatostatin receptors, CCK-2 receptors might be viable targets for radionuclide scintigraphy and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed, and some have been carried through into clinical studies. However, these studies are mostly limited and difficult to compare. The aim of this study was to evaluate the diagnostic and therapeutic potential of three promising CCK-2 receptor-binding radiopeptides in patients with MTC. Methods: 111In-DOTA-(D)Asp-Tyr-Nle-Gly-Trp-Nle- Asp-Phe-NH2 (111In-DOTA-CCK), a CCK analogue, and the gastrin-based ligands 99mTc-N4-Gly-(D)Glu-(Glu) 5-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (99mTc- demogastrin 2) and 111In-DOTA-(D)Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe- NH2 (111In-DOTA-MG11) were each administered to the same group of six patients. Planar images made at 3-5, 7 and 24 h p.i. were used for comparison of tumour visualisation and renal uptake. Results: 99mTc-demogastrin 2 scintigraphy visualised all known lesions and new lesions in four of six patients. 111In-DOTA-CCK and 111In-DOTA-MG11 on the other hand missed several lesions; tumour uptake of these two radiopharmaceuticals was quite low. Comparison of retention of renal activity showed no major differences between the three radiopeptides. Conclusion: 99mTc-demogastrin 2 scintigraphy appeared most promising as a diagnostic tool in patients with MTC. Further studies are required to evaluate its value in patient management. Direct comparisons of the compounds studied strongly suggests that 111In-DOTA-CCK and 111In-DOTA-MG11 have less potential as imaging agents than 99mTc-demogastrin 2. These DOTA-linked compounds are considered unlikely to be useful for radionuclide therapy because of low tumour uptake.

Treatment with the radiolabeled somatostatin analog [177Lu- DOTA0,Tyr3]octreotate: Toxicity, efficacy, and survival (Article)

2008-09-22T00:00:00Z

Purpose: Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slowgrowing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients. Patients and Methods: Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients. Results: Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Complete and partial tumor remissions occurred in 2% and 28% of 310 GEPNET patients, respectively. Minor tumor response (decrease in size > 25% and < 50%) occurred in 16%. Median time to progression was 40 months. Median OS from start of treatment was 46 months, median OS from diagnosis was 128 months. Compared with historical controls, there was a survival benefit of 40 to 72 months from diagnosis. Conclusion: Treatment with [177Lu-DOTA0, Tyr3]octreotate has few adverse effects. Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities. Compared with historical controls, there is a benefit in OS from time of diagnosis of several years.

Somatostatin receptor subtype 2-mediated uptake of radiolabelled somatostatin analogues in the human kidney (Article)

2007-11-01T00:00:00Z

Purpose: Renal irradiation is a dose-limiting factor in peptide receptor radionuclide therapy using radiolabelled somatostatin analogues. This irradiation is mainly caused by reabsorption of radiolabelled peptides in the proximal tubule. In the human kidney, somatostatin receptors are expressed in the vasa recta, tubuli and glomeruli. It is not clear to what extent these receptors contribute to the total kidney radioactivity uptake. Methods: Retrospectively, [111In-DTPA0]octreotide scans of ten selected patients with carcinoids (well-differentiated gastrointestinal endocrine tumour) with liver metastases were evaluated. For each patient, two scans were obtained: one scan was performed without (control) and one during treatment with unlabelled octreotide. Kidney, tumour, spleen and liver uptake was measured in both scans. Results: The interval between the two scans per patient varied from 50 to 397 days. Octreotide treatment substantially lowered kidney [111In-DTPA0]octreotide uptake in eight out of ten patients. Kidney uptake in all patients was reduced to 82%±15% of control, (p<0.01). A correlation between kidney uptake and spleen uptake was found (r=0.67, p<0.05). Serum creatinine was unchanged. Surprisingly, tumour and liver [111In-DTPA0]octreotide uptake was not significantly influenced by unlabelled octreotide therapy, but spleen uptake was significantly lowered by treatment (30.6% of control, p<0.002). Conclusion: We conclude that the somatostatin receptor plays a role in the total renal uptake of radiolabelled somatostatin analogues. The long interval between scans might explain the finding that tumour and liver metastasis uptake of [111In-DTPA0]octreotide was unchanged. Further studies are needed to confirm and eludicate the results of this study.

Clinical validation of fully automated computation of ejection fraction from gated equilibrium blood-pool scintigrams (Article)

1983-01-01T00:00:00Z

A fully automated procedure for the computation of left-ventricular ejection fraction (EF) from cardiac-gated Tc-99m blood-pool (GBP) scintigrams with fixed, dual, and variable ROI methods is described. By comparison with EF data from contrast ventriculography in 68 patients, the dual-ROI method (separate end-diastolic and end-systolic contours) was found to be the method of choice; processing time was 2 min. Success score of dual-ROI procedure was 92% as assessed from 100 GBP studies. Overall reproducibility of data acquisition and analysis was determined in 12 patients. Mean value and standard deviation of differences between repeat studies (average time interval 27 min) were 0.8% and 4.3% EF units, respectively, (r = 0.98). We conclude that left-ventricular EF can be computed automatically from GBP scintigrams with minimal operator-interaction and good reproducibility; EFs are similar to those from contrast ventriculography.