Comparison of 111In-[DTPA0]Octreotide Versus Non Carrier Added 177Lu- [DOTA0,Tyr3]-Octreotate Efficacy in Patients With GEP-NET Treated Intra-arterially for Liver Metastases.

AIM: In patients with progressive, metastatic neuroendocrine tumors (NET), intra-arterial radionuclide infusions with high activities of In-[DTPA]-octreotide and more recently with non-carrier added (nca) Lu-[DOTA,Tyr]-octreotate have been performed with encouraging results. However, the affinity profiles (IC50) of these radiopeptides for human sst2 receptors are markedly different (In-[DTPA]-octreotide, 22 ± 3.6 nM and nca Lu-[DOTA,Tyr]-octreotate, 1.5 ± 4.0 nM). The total administered activity is determined by organ dose limits (kidneys and bone marrow), and our aim therefore was to compare and evaluate the therapeutic efficacy of both radiopeptides in metastatic NETs. METHODS: Thirty patients with gastroenteropancreatic (GEP) somatostatin-positive NETs with liver metastases confirmed on biopsy and In-pentetreotide scan were included. They were treated with In-[DTPA]-octreotide (n = 17) or nca Lu-[DOTA,Tyr]-octreotate (n = 13). Blood samples were collected 2, 4, 8, and 24 hours postadministration to calculate residence time in blood and in red marrow. The maximum percentage uptake in organs and tumors was estimated by region of interest analysis, and tumor dosimetry calculations were performed using OLINDA/EXM/ 1.0 software. RESULTS: ncaLu-[DOTA,Tyr3]-octreotate blood radioactivity, expressed as a percentage of the injected dose, was significantly lower than In-[DTPA]-octreotide (P < 0.05), as clearly depicted from the time-activity curves; the background-corrected tumor uptake was significantly higher than In-[DTPA]-octreotide but without any significant difference in other organs (spleen, kidneys, and liver). CONCLUSIONS: Using Lu-[DOTA,Tyr]-octreotate, a 3-fold higher absorbed dose to tumor tissue was achieved compared with In-[DTPA] octreotide. Residence time of nca Lu-[DOTA,Tyr]-octreotate results in a significantly higher absorbed dose to bone marrow compared with In-[DTPA]-octreotide. However, a drawback of In-[DTPA]-octreotide therapy is that the number of administrations would need to be almost doubled to achieve an equal therapeutic outcome as compared with Lu-[DOTA,Tyr]-octreotate.

Super-selective hepatic arterial infusions as established technique ('ARETAIEION' Protocol) of [177Lu]DOTA-TATE in inoperable neuroendocrine liver metastases of gastro-entero-pancreatic (GEP) tumors.

AIM: Aim of this study was to evaluate the effectiveness of non-carrier added (n. c. a.) [177Lu]DOTA-TATE in inoperable liver metastases, positive for sst2 receptor overexpression (verified by Octreoscan and confirmed by biopsy) due to neuroendocrine gastroenteropancreatic (GEP) tumors. [177Lu]DOTA-TATE has been infused after selective catheterization of the hepatic artery, minimising in parallel the toxicity of non-target tissues. METHODS: The dose per session administered to each patient (12 cases in total) was 7400 MBq (200 mCi). Repetitions did not exceed 6-fold with treatment intervals of 5-8 weeks. Response assessment was classified according to the therapeutic benefit. Absorbed doses delivered to metastases, kidneys and red marrow were calculated according to OLINDA 1.1 program and the derived values were correlated to the Response Evaluating Criteria in Solid Tumors (RECIST). CT/MRI scans were performed as baseline before, during and after the end of treatment and monthly ultrasound images for follow-up estimation and measurements. Toxicity (World Health Organization criteria) was measured using blood and urine tests of renal, hepatic and bone marrow function. RESULTS: None of the patients resulted complete response (0.0%); partial response was assessed in 8 (66.7%), disease stabilization in 3 (25%) and progressive disease in 1(8.3%). A 14-month median survival time was estimated for all patients, so far. Eight of 12 (66.7%) showed a mean target diameter shrinkage ranging from 33% to 45%. The organ average radiation dose estimation was found as follows: a) liver tumor 20.8 mGy/MBq; b) liver 0.14 mGy/MBq; c) kidneys 0.41 mGy/MBq; d) spleen 1.4 mGy/MBq; and f) bone marrow 0.022 mGy/MBq. The average absorbed dose per session to a tumor for a spherical mass of 20 g was estimated to be 20.8 mGy/MBq, depending on the histotype of the tumor. WHO toxicity grade 2 to 3 erythro-, leuko- and thrombo-cytopenia occurred in 9 (75%) cases observed about after the third session. CONCLUSION: In unresectable metastatic liver lesions positive for somatostatin receptors repeated, trans-hepatic high doses of [177Lu]DOTA-TATE resulted in a more than promising therapeutic outcome with a partial response in 75% of the treated patients. Given the loco-regional modality character of the administration technique, no nephro-toxicity has been so far observed whereas a remarkable myelotoxicity was noticed.

Introduction of a new semi-quantitative index with predictive implications in patients with painful osseous metastases after (186)Re-HEDP therapy.

AIM: In this study, a new method has been used to predict pain response to (186)Re-HEDP therapy in patients suffering from painful osseous metastases, on the basis of a modified bone scan index and pre-therapy pain scoring. METHODS: Forty five patients received a total of 73 doses of (186)Re-HEDP during a period of pain relapse without extra-osseous disease progression. All patients were under stable regimen of zoledronic acid, far off other therapeutic manipulations. Imaging studies regarding a modified estimation of bone scan index, were applied; the value of the largest bony lesion (called mBSI), provided that it also corresponded to the most prominent site of osseous pain was taken into account, and a new semi-quantitative index called Double Product Value (DPV), equal to pre-therapy pain score times mBSI was entered in the result analyses, to investigate any possible correlations with response endpoints. RESULTS: Favourable response occurred in 35/47 evaluated therapeutic doses of (186)Re-HEDP (74.5%; excellent response in 12 doses, 25.5%). Responders had significantly lower DPV (3.4 ± 2.3 vs. 10.2 ± 6.2, P=0.0029, for non-responders). Patients with pre-therapy DPV 4, and also a longer median period of pain relief (respective mean values 5.9 versus 2.1 months, HR 2.82; P=0.0001). CONCLUSION: DPV, as developed and implemented in this study proved a valuable and reproducible pre-therapy tool for assessing degree and duration of pain response after (186)Re-HEDP therapy.

Predictive value of the clinically and scintigraphically important bone lesions in hormone-refractory prostate cancer (HRPC)

No disponible

Optimization of doses received by the hospital staff and the members of the family of patients undergoing 111In-DTPA-D-Phe1-Octreotide therapy.

According to the Euratom Directives (96/29, 97/43), the doses received by the workers as well as the family of patients and third persons during medical exposures, should conform to the dose constraint levels (DCLs), established by the authorities for each group in the context of optimisation. This study deals with the implementation of a radiation protection protocol, concerning the aforementioned group members for patients undergoing treatment with 111In-DTPA-D-Phe1-Octreotide, after intra-arterial infusion. It is shown that by applying this protocol the annual doses to the medical and technical staff are considerably reduced and remain below the established DCLs. Following the post-release behaviour instructions given to the patient, doses to the family and third persons may be kept lower than the corresponding DCLs provided by the National Regulations.

Somatostatin receptor scintigraphy of non-neuroendocrine malignancies with 111In-pentetreotide.

In-111 pentetreotide is a new radiolabelled [OctreoScan 111, Mallinckrodt Medical BV, Petten] somatostatin analog with high affinity to somatostatin receptors (SR). introduced for the in vivo imaging of SR positive tissues. In an attempt to evaluate its clinical usefulness for tissue characterization in malignancies without neuroendocrine expression in parallel with histological and radiological examinations, specific scintigraphy was performed on brain (6 cases), thyroid (6 cases) and breast (9 cases) tumors, and in lymphomas (9 cases) and melanomas (6 cases). A dose of 111MBq of In-111 pentetreotide was injected i.v. to each patient and scintimages at 6 and 22 hours (for comparison) p.i. were obtained. The primary lesion of the breast cancer population was imaged in all 9 cases as well as all the palpable axillary nodes in 4 cases. Three women with impalpable axillary lymph nodes scanned negative but had a positive biopsy. Both meningiomas were positive for SR scans: positive results were also obtained for the high grade astrocytoma and the craniopharyngioma: Two out of 6 patients with papillary thyroid cancer showed a marked radiotracer accumulation. Scintigraphy in all 5 lymphomas was positive for SR but did not detect the Tc-99m sulphur microcolloid [Lymphoscint, Solco, Basel, Suitzerland] imaged lymph nodes in 5 melanomectomized patients. When judging the imaging results of these non-neuroendocrine malignancies definite conclusions should not be drawn since the number of studied cases polymorph, was small for every cancer histotype; nevertheless SR scintigraphy does not seem to be reliable for tumor staging in non-neuroendocrine malignancies, but is more suitable for a tissue characterization and monitoring changes of SR expression during and after therapy.

Comparison of In-111 pentetreotide, Tc-99m (V)DMSA and I-123 mlBG scintimaging in neural crest tumors.

Three radiolabelled substances, 111In-pentetreotide, 99mTc-(V)DMSA and 123I-MIBG with different kinetics but similar tumor seeking behavior, were i.v. injected to assess and correlate their clinical value in metastatic malignant pheochromocytomas (4 patients), stage III and IV neuroblastomas (7 patients) and medullary thyroid carcinomas (6 patients). All II pheochromocytoma/neuroblastoma patients received i.v. a dose of III MBq (3 mCi) of 123I-MIBG and 185 MBq (5 mCi) of 111In-pentetreotide, within approximately weeks each other. Furthermore, in 4 of these patients as well as in all medullary thyroid carcinoma patients 111 MBq (3 mCi) of 99mTc-(V)DMSA were applied i.v. I week prior to the pentetreotide/mlBG scans. Four patients (malignant pheochromocytoma) with a total of 7 foci showing MIBG accumulation had 3 sites with pentetreotide and 1 site with (V)DMSA uptake, while in 7 patients (neuroblastora) with 15 foci showing MIBG accumulation 10 sites had detectable pentetreotide and 3 sites detectable (V)DMSA. Of the three radiotracers, 111In-pentetreotide used for somatostatin receptor identification holds promise mainly in cases where foci imaged with 123I-MIBG are negative. 111In-pentetreotide is unlikely to replace 123I-MIBG as a first-line routine diagnostic scintigraphic modality; compared to pentetreotide or MIBG, (V)DMSA seems to be highly sensitive only in medullary thyroid carcinomas.

99mTc-antigranulocyte bone marrow scintigraphy of breast and prostate skeletal metastases.

Although bone scintigraphy using Tc-99m labelled diphosphonates is a highly sensitive modality for the detection of of the extent of secondary skeletal malignancies, it is often not sufficient since possible bone marrow participation cannot be imaged We make a preliminary report on the usefulness of bone marrow immunoscintigraphy in the follow-up of patients with skeletal metastases due to breast and prostate cancer in parallel with the interpretation of conventional Tc-99m MDP bone scans. Approximately 7 to 9 months after radionuclide therapy both Tc-99m MDP [Hellenic Nuclear Research Center "Democritos". Aghia Paraskevi, Attikil and Tc-99m Anti-Granulocyte BW 250/183 [CIS Bio International, Gif sur Yvette, France] bone scans were performed on 2 prostate cancer patients and 5 women with breast cancer with disseminated bone metastases. Bone scans preceded bone marrow scans. Bone marrow defects were concordant with cortical scans in 4 cases, while they were larger in 4 sites compared to -MDP scan. Four sites in the ribs, shown on -MDP scan could not be detected on antigranulocyte scans. Bone cortex and marrow combined imaging of osseous metastases using different radiotracers increases the information on the real extent of skeletal involvement; the scintigraphic data obtained are valuable for the further decision making for the best possible management of unexpected myelosuppressive side effects as well as the follow-up of the treated cancer patients.

Two phase scintigraphic mapping of lymphatic drainage in cutaneous melanoma using 99mTc-sulfur microcolloid/99mTc antimelanoma antibody.

The purpose of lymphoscintigraphy in patients with melanoma before surgery is to image the lymphatic drainage net and particularly to detect the sentinel node; the purpose of immunolymphoscintigraphy after surgery is to map the lymphatic drainage and to detect a possible spead of the malignancy towards the lymph nodes surrounding the surgical field or more distal regions. The aim of the present study was to assess the sensitivity of a two-phase procedure with Tc-99m-Iabelled agents for exploring possible spread of melanoma after thorough resection of the primary lesion. Seven melanomectomized patients were enrolled into the study. The melanomas were situated on the head, back, arm and buttock of these patients. Intracutaneous lymphoscintigraphy with Tc-99m sulphur microcolloid [Lymphoscint, Solco, Basel, Switzerland] and i.v. immunoscrintigraphy with Tc-99m-antimelanoma antibody [Tecnemab-K-I, Sorin Biomedica Spa, Saluggia, Italy] at a dosage of 55 MBq and 740 MBq respectively, were performed in 13 patients to define possible infiltration of lymph nodes after surgery with a time interval of 1 week between the two examinations. Tc-99s sulphur microcolloid preceded the Tc-99m anti-melanoma antibody scan. The scintigrams were evaluated by three experienced nuclear physicians. The method detected 3 out of 16 suspicious nodes as malignant. Combined two-phase technique improves the diagnostic and staging accuracy of cutaneous melanoma affected population and appears extremely useful in the surgical confrontation of the lymphatic spead.

Renal cell carcinoma detection and systemic therapy with tumour-affine gallium-67 and with yttrium-90 citrate solutions.

BACKGROUND: There have been no major advances in the systemic detection of renal cell carcinoma (RCC) and its unpredictable metastases. Surgery, thus, remains the mainstay of the curative treatment for the localized disease. The propose of the present study has been to systemically detect and treat advanced RCC respectively with Ga-67 and Y-90 radiopharmaceuticals containing tumour-affine species. PATIENTS AND METHODS: Thirty-three RCC patients were imaged with Tc-99m-MDP and then with Ga-67 citrate solution in order to detect RCC and its metastases. Yttrium-90 citrate solution, containing the radionuclide species chromatographically and electrophoretically identical to those in RCC-affine Ga-67 solution, was administered i.v. for systemic therapy of advanced RCC. Total-body distribution of Y-90 was studied with a gamma-camera equipped with an ultra-high-sensitivity collimator. The efficacy of the therapy was studied by the clinical condition of the patient and by the total-body scintigraphic imaging with Tc-99m-MDP and with Ga-67 citrate solution. RESULTS: Ga-67 detects RCC bone metastases better than Tc-99m-MDP. Systemic therapy of RCC metastasized to bones, lung and brain was obtained with RCC-affine Y-90 citrate solution. CONCLUSIONS: Third group metal radionuclides, Ga-67 and Y-90, detect and treat advanced RCC.

Advanced prostate cancer diagnosis and therapy with gallium-67 and yttrium-90, respectively.

BACKGROUND: Androgen deprivation therapy remains so far the mainstay of advanced prostate cancer treatment. Although it improves the quality of life of the patient for some time, the disease progresses and soon it becomes hormonally unresponsive. The object of our research has been to find a systemic therapy for prostate cancer patients whose disease no longer responds to hormone therapy, radiation therapy, chemotherapy and immunotherapy. PATIENTS AND METHODS: Thirty-one advanced prostate cancer patients with intense bone metastasis pain, bed ridden, and with permanent urinary catheter were first examined with Ga-67 and then treated with Y-90 solutions which were chromatographically and electrophoretically analysed for the presence of both cationic and anionic species of the radionuclide. The quality of life and prostate specific antigen (PSA values) values were followed for testing the success of the therapy. RESULTS: Prostate cancer-affine Y-90 cured the advanced prostate cancer patients who regained their normal life. The uptake of the radionuclide in the primary cancer and its metastases responsible for the treatment has been confirmed by scintigraphy. CONCLUSIONS: Prostate cancer-affine Y-90 solution, containing stable cationic and anionic species of the radionuclide, is effective in the cure of advanced prostate cancer patients.

Palliative therapy using rhenium-186-HEDP in painful breast osseous metastases.

The efficacy and toxicity of treatment with 1400 +/- 100 MBq of Re-186-HEDP were evaluated in women with osseous metastatic breast cancer. The follow-up period was fourteen weeks. The efficacy of treatment was assessed by a) a pain and performance questionnaire that patients were asked to complete daily and b) a CT scan comparison of a randomly preselected osseous lesion before and 30 weeks after Re-186-HEDP i.v. application. The response to treatment was also evaluated by using the Kamofsky Index. Two out of fourteen women (14%) experienced loss of pain, 6 experienced obvious and 2 some improvement. No change was observed in 4 patients. Five patients manifested a flare response to treatment, with increase in pain within the first, 4 to 5 days after Re-186-HEDP administration. Five patients showed a decrease in platelet levels and absolute number of polymorphonuclear blood transfusion; no neurologic side effects were observed. Re-186-HEDP appears to be a useful new radiopharmaceutical for pain palliation induced by osseous metastases due to breast cancer. Compared to Sr-89 chloride efficacy, it provides longer-lasting analgesia, and when needed it can be reinjected with less risk due to its improved physico- and radiochemical properties.

Gastric uptake during Re-186 HEDP bone scintigraphy.

In bone scintigraphy extraosseous uptake of the radiopharmaceutical (TcO4-, pertechnetate) is a common finding when the stomach is abnormally observed; this may be due to the instability of the radiopharmaceutical leading to free pertechnetate within this organ. The same explanation might be inculpate rhenium 186-HEDP, due to its similarity to Tc-99m MDP's sphysicochemical properties and behavior, as both radioisotopes are Group VII metals /1/ and are labelling the same ligand (a diphosphonate moiety). We report on 186Re-HEDP uptake in the stomach in two patients with osseous metastases because of prostate and breast cancer respectively out of a series of 52 cancer affected individuals, treated with 186Re-HEDP. The thorough clinical and laboratory investigation of both patients assessed that this extraosseous radio-rhenium accumulation was multifactorial with the main cause being a disturbance of body fluid acid-balance, favoring calcium and phosphate ion precipitation and leading to 186Re-HEDP extraosseous uptake.

Effects in the testes after SPECT myocardial perfusion with Tl-201 or Tc-99m hexaMIBI.

Thallium-201 with a half-life of 73 hours, decays by electron capture and as a consequence emits numerous Auger electrons. When it localises in the cell nucleus it causes enhanced biological effects. Technetium-99m with a half-life of 6 hours, radiates gamma rays and the side effects are not as significant. Tl-201 and Tc-99m labelled with SESTAMIBI are used for the SPECT perfusion image of the heart. In this study the tissue of interest are the testes which, after irradiation, can develop stochastic effects: both somatic (cancer) and hereditary. The activities of the radiopharmaceuticals used in common practice (30 mCi of Tc-99m and 3 mCi of Tl-201) cause different probabilities for the induction of stochastic effects in the testes. The probabilities are about 30 times higher for Tl-201 than for Tc-99m. These results, in combination with the fact that the higher activity of Tc-99m yields better images within shorter time, must make the clinician carefully assess the choice of the radiopharmaceutical to be used for the studies of the heart, especially for patients of reproductive age.

Receptor scintigraphy of non-neuroendocrine cancers with In-111 pentetreotide.

Somatostatin receptors (SR) are surface markers characterizing not only APUDomas associated with neuroendocrine identities but also malignancies without neuroendocrine expression. Recently, the somatostatin analog pentetreotide was labeled with In-111 (OctreoScan 111, Mallinckrodt Medical BV, Petten, Holland) and introduced for the in vivo visualization in man of SR-positive tissues. In the present report, SR-specific scintigraphy is evaluated as a clinical tool for tissue characterization in correlation with histological and radiological examinations. Scintigraphy was focused and performed in cancer types without neuroendocrine tissue expression such as brain (n = 6) and breast tumors (n = 9) and lymphomas (n = 5). Scintigraphy was performed for comparison at 6 and 22 h after i.v. application of 111 MBq (3 mCi) of In-111-Pentetreotide. In the breast cancer group, the primary tumor was visualized in all 9 women as well as in all 4 cases with palpable axillary lymph nodes. Three women with a negative axillary node scan and impalpable nodes had positive biopsy. In two cases, mediastinal lymph node involvement was observed. So far the role of SR-positive breast cancer (BC) scans remains unknown. It is tempting to speculate that in resected women who are histologically and scintigraphically SR positive, it might be of value in the early detection of symptom-free recurrences. High densities of SR were present within both meningiomas, the high-grade astrocytoma and the craniopharyngioma. Differentiation of low- and high-grade astrocytomas could not be successfully achieved because both grades showed intense radioactivity uptake, even though high-grade tumors lack SR. The latter might be due to the damaged blood-brain barrier and the poor radioactivity washout observed in high-grade astrocytomas. All five lymphomas could be detected due to the presence of activated lymphocytes and macrophages that express SR at a sufficient density. In conclusion, SR scintigraphy in non-neuroendocrine malignancies does not seem to be reliable for an initial tumor staging but rather more suitable for a tissue characterization and extremely useful for monitoring changes of SR expression after treatment.

[Long term biokinetics of 169Yb following injection as citrate, hydroxyethylethylenediaminetetraacetate and nitrilotriacetate]. / Langzeitbiokinetik des 169Yb nach Injektion als Zitrat, Hydroxyethylethylen-diamintetraazetat und Nitrilotriazetat.

169Yb complexes with known biokinetics in tumour-bearing mice up to 48 h p.i. were injected into healthy mice to study the radionuclide biodistribution in various organs and tissues for 672 h after injection, in order to obtain reliable biokinetic data in an animal model, not affected by tumour-growth, as a basis for the calculation of biological half-life and dose distribution. The results demonstrated the existence of at least two components with different biological half-lives in the organs and tissues investigated. The effective half-lives of these components decreased with increasing stability of the complexes administered. The effective half-life of the fast component was a few hours and that of the slow one between about 200 and 800 h.

[The effect of ethylenediaminetetramethylenephosphonate on the biodistribution of tumor-seeking radionuclides]. / Der Einfluss von Ethylendiamintetramethylenphosphonat auf die Bioverteilung tumoraffiner Radionuklide.

It is well known that after application of radioactive complexes for tumour diagnosis or therapy, such as 67Ga-citrate or radiolanthanide complexes (167Tm- or 169Yb-nitrilotriacetate, -citrate, -alpha-hydroxyisobutyrate, 90Y-citrate, etc.) activity is accumulated not only in the tumour but also in other organs, above all liver and bone. This is the main obstacle to their medical use. Recently published results encouraged us to use ethylenediaminetetramethylene phosphonate (EDTMP) for the reduction of extratumoural liver activity. The results show that even small amounts of EDTMP (1-2 mg/kg BW) reduce the activity deposition in the liver by about one order of magnitude. EDTMP provoked elimination of activity from tumour, skeleton and other tissues but not to the same extent as from the liver. Tumor/liver activity ratios > 5 are achievable in this manner.

[The effect of bone-seeking metal salts on the biodistribution of tumor-seeking heavy metal complexes]. / Der Einfluss von knochenaffinen Metallsalzen auf die Bioverteilung tumoraffiner Schwermetallkomplexe.

This work attempted to overcome the problem of unwanted bone radioactivity after injection of tumour-affine heavy-metal compounds (prototype 169Yb-citrate) by pre-application of stable yttrium- and calcium-compounds into tumour-bearing mice in doses of 1 mg metal/kg body weight. The pre-application of stable yttrium and calcium resulted in a smaller bone radioactivity. The most favourable results were achieved by injecting the metal salts simultaneously at or within 5 h before the 169Yb-citrate. On the other hand a strong radioactivity increase in the RES (liver and spleen) by a factor of 2 to 4 was observed after yttrium-preapplication.

[The effect of Ca-diethylenetriamine pentaacetate on the bio-behavior of tumor-affine metal complexes]. / Der Einfluss von Ca-Diethylentriaminpentaacetat auf das Bioverhalten tumoraffiner Metallkomplexe.

The complexon CaDTPA was injected into tumour-bearing mice in concentrations of 0.05, 0.1, 0.3, and 0.6 mole/l (pH:6) 30 min after the 169Yb-injection. 100 microliters of a 0.3 M CaDTPA solution were injected at different time points (simultaneously, 2, 5, 10, 20, 30, 40 and 50 min, 1, 1.25, 1.5, 2.5 and 10 h) after 169Yb-citrate injection. The animals were killed 24 h after radionuclide administration. A strong radioactivity decrease was observable 24 h p.i. not only in blood, liver, spleen, muscle and bone but also in the tumour if CaDTPA was administered within the first 2 h after ytterbium injection. Thereafter no change in radioactivity could be achieved by DTPA. A time phase in which the Yb could be eliminated from the tissues by means of DTPA (time intervals < 2 h) was distinguishable from a time phase in which it was not attainable for DTPA (time intervals > 5 h). This indicates that the incorporation of Yb into the cells is completed after 5 h and that the metals are intracellularly bound, probably to the lysosomes. Improvements of the scintigraphic tumour detection cannot be expected from the use of complexons.