Oncological outcomes of open, laparoscopic and robotic colectomy in patients with transverse colon cancer.

BACKGROUND: Literature concerning surgical management of transverse colon cancer is scarce, since many key trials excluded transverse colon cancer. The aim of this study was to evaluate clinical and oncological outcomes comparing open, laparoscopic and robotic transverse colon cancer resection. METHODS: Consecutive patients who underwent elective surgery for transverse colon cancer between December 2005 and July 2021 were included. Data were kept in a prospective database approved by the institutional ethics committee. Primary outcome was overall and disease-free survival. Secondary outcomes included complications, operative time, length of stay and lymph node harvest. Statistical analysis was corrected for age and tumour localisation. RESULTS: Two hundred and forty-six (38 robotic, 71 open and 137 laparoscopic resections) were recruited in this study. There were five conversions during laparoscopic procedures. Operative time was significantly shorter in robotic vs laparoscopic procedures (195 vs 238 min, p = 0.005) and length of stay was shorter in robotic vs laparoscopic and open group (7 vs 9 vs 15 days, p < 0.001). There was no difference in overall complications. R0 resections were similar. Lymph node harvest was highest in the robotic group vs. laparoscopic or open (32 vs. 29 vs. 21, p < 0.001). Overall survival was 97%, 85% and 60% (p < 0.001) and disease-free survival was 91%, 78% and 56% (p < 0.001) for the robotic, laparoscopic and open groups, respectively. CONCLUSIONS: Minimally invasive surgery for transverse colon cancer is safe and offers good clinical and oncological outcomes. Robotic resection is associated with significantly shorter operating times, higher lymph node harvest, lower conversion rate and does not increase morbidity. Differences in disease-free and overall survival should be further explored in randomised controlled trials.

Laparoscopic Versus Robot-Assisted Versus Transanal Low Anterior Resection: 3-Year Oncologic Results for a Population-Based Cohort in Experienced Centers.

BACKGROUND: Laparoscopic, robot-assisted, and transanal total mesorectal excision are the minimally invasive techniques used most for rectal cancer surgery. Because data regarding oncologic results are lacking, this study aimed to compare these three techniques while taking the learning curve into account. METHODS: This retrospective population-based study cohort included all patients between 2015 and 2017 who underwent a low anterior resection at 11 dedicated centers that had completed the learning curve of the specific technique. The primary outcome was overall survival (OS) during a 3-year follow-up period. The secondary outcomes were 3-year disease-free survival (DFS) and 3-year local recurrence rate. Statistical analysis was performed using Cox-regression. RESULTS: The 617 patients enrolled in the study included 252 who underwent a laparoscopic resection, 205 who underwent a robot-assisted resection, and 160 who underwent a transanal low anterior resection. The oncologic outcomes were equal between the three techniques. The 3-year OS rate was 90% for laparoscopic resection, 90.4% for robot-assisted resection, and 87.6% for transanal low anterior resection. The 3-year DFS rate was 77.8% for laparoscopic resection, 75.8% for robot-assisted resection, and 78.8% for transanal low anterior resection. The 3-year local recurrence rate was in 6.1% for laparoscopic resection, 6.4% for robot-assisted resection, and 5.7% for transanal procedures. Cox-regression did not show a significant difference between the techniques while taking confounders into account. CONCLUSION: The oncologic results during the 3-year follow-up were good and comparable between laparoscopic, robot-assisted, and transanal total mesorectal technique at experienced centers. These techniques can be performed safely in experienced hands.

Comparison of laparoscopic versus robot-assisted versus transanal total mesorectal excision surgery for rectal cancer: a retrospective propensity score-matched cohort study of short-term outcomes.

BACKGROUND: Laparoscopic total mesorectal excision (TME) surgery for rectal cancer has important technical limitations. Robot-assisted and transanal TME (TaTME) may overcome these limitations, potentially leading to lower conversion rates and reduced morbidity. However, comparative data between the three approaches are lacking. The aim of this study was to compare short-term outcomes for laparoscopic TME, robot-assisted TME and TaTME in expert centres. METHODS: Patients undergoing rectal cancer surgery between 2015 and 2017 in expert centres for laparoscopic, robot-assisted or TaTME were included. Outcomes for TME surgery performed by the specialized technique in the expert centres were compared after propensity score matching. The primary outcome was conversion rate. Secondary outcomes were morbidity and pathological outcomes. RESULTS: A total of 1078 patients were included. In rectal cancer surgery in general, the overall rate of primary anastomosis was 39.4, 61.9 and 61.9 per cent in laparoscopic, robot-assisted and TaTME centres respectively (P < 0.001). For specialized techniques in expert centres excluding abdominoperineal resection (APR), the rate of primary anastomosis was 66.7 per cent in laparoscopic, 89.8 per cent in robot-assisted and 84.3 per cent in TaTME (P < 0.001). Conversion rates were 3.7 , 4.6 and 1.9 per cent in laparoscopic, robot-assisted and TaTME respectively (P = 0.134). The number of incomplete specimens, circumferential resection margin involvement rate and morbidity rates did not differ. CONCLUSION: In the minimally invasive treatment of rectal cancer more primary anastomoses are created in robotic and TaTME expert centres.

The results of this study showed similar and acceptable short-term results for laparoscopic, robot-assisted and transanal total mesorectal excision performed in expert centres. In centres with robot-assisted or transanal technique, more primary anastomoses were made.

Partial liver resection because of bile duct injury.

AIM: To analyze the outcome of partial liver resection (PHx) after bile duct injury (BDI) in patients after multimodality treatment. METHODS: Between 1990 and 2012, 800 BDI patients were referred to our tertiary center. Patient characteristics and long-term outcomes were described. RESULTS: PHx was performed in 11 patients (1.4%), mean age 48.3 years (range 29.3-83.5 years), mainly because of complex injury [Amsterdam classification type D (n = 10, 91%), Strasberg type E (n = 7, 64%) and Bismuth type IV (n = 8, 73%)]. In 7 patients (64%), concomitant vasculobiliary injury had occurred in the right hepatic artery (n = 3), proper hepatic artery (n = 1), portal vein (PV; n = 2) and the right hepatic artery and PV simultaneously (n = 1). Early PHx was performed in 2 patients and delayed resection in 9 patients after a median of 57.8 months (range 3.9-183.4 months). The in-hospital mortality was 18% (n = 2) and long-term mortality 9% (n = 1). There were no significant differences in postoperative complications between early and late resection. CONCLUSIONS: Indications for PHx after BDI in patients referred to a tertiary center are relatively low (1.4%) and generally apply to vasculobiliary injury. The implications for treatment are important, so it is worthwhile to classify vascular injuries in the management of BDI.

Do videos improve website satisfaction and recall of online cancer-related information in older lung cancer patients?

OBJECTIVE: This study investigated the effects of personalized audiovisual information in addition to text on website satisfaction and recall of cancer-related online information in older lung cancer patients. METHODS: An experiment using a 3 (condition: text only vs. text with nonpersonalized video vs. text with personalized video) by 2 (age patient: younger [<65 yrs] vs. older [≥65 yrs]) between-subjects factorial design was conducted. Patients were randomly assigned to one of the three information conditions stratified by age group. RESULTS: Patients were more satisfied with the comprehensibility, attractiveness, and the emotional support from the website when information was presented as text with personalized video compared to text only. Text with personalized video also outperformed text with nonpersonalized video regarding emotional support from the website. Furthermore, text with video improved patients' recall of cancer-related information as compared to text only. Older patients recalled less information correctly than younger patients, except when we controlled for Internet use. CONCLUSION: Text with personalized audiovisual information can enhance website satisfaction and information recall. Internet use plays an important role in explaining recall of information. PRACTICE IMPLICATIONS: The results of this study can be used to develop effective health communication materials for cancer patients.

Combined fractures of the distal radius and scaphoid.

Combined fractures of the distal radius and scaphoid are uncommon, are usually the result of a high-energy trauma and there is no consensus regarding their optimal management. We present a retrospective study of ten patients, out of whom nine underwent internal fixation of their fractures. Open reduction and internal fixation were performed in six of the eight intraarticular fractures of the distal radius. After a mean follow-up of 40 months, eight patients reported no pain and the mean range of wrist motion was 55 degrees flexion and 71 degrees extension. Our current management protocol is outlined. Emphasis on treatment of this combined fracture should be placed on the management of the distal radius fracture. Internal fixation of both fractures, followed by early rehabilitation, optimises outcomes. Cast treatment is indicated only in patients with completely undisplaced fractures of both the radius and the scaphoid.

[Invasive infection with Moraxella catarrhalis in two children with lymphatic leukemia and granulocytopenia]. / Invasieve infectie met Moraxella catarrhalis bij twee kinderen met lymfatische leukemie en granulocytopenie.

In two young children with leukaemia, a girl and a boy aged 5 and 4 years, respectively, an invasive infection due to Moraxella catarrhalis was diagnosed at the time of granulocytopenia. They were treated with antibiotics. The first child developed pneumonia and recovered, the other developed severe septic shock and died. M. catarrhalis is a Gram-negative diplococcus, frequently colonising the upper respiratory tract in young children. In childhood this pathogen mainly causes infections such as otitis media and sinusitis, while in adults it primarily causes laryngitis, bronchitis and pneumonia. Immunocompromised patients or patients with chronic cardiopulmonary disease have an increased risk of severe infections.

A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients.

Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in neuroblastoma patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG uptake and provide a relatively low number of 6,300 binding sites/cell for mAb chCE7. Tumours were treated with single injections of 131I-MIBG (110 MBq) and with 131I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with 131I-chCE7, the subcutaneous tumours nearly disappeared; treatment with 131I-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumour regrowth delay of 9 days occurred with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35, which does not bind to SK-N-SH cells, compared with a regrowth delay of 34 days with 131I-mAb chCE7 and of 24 days with 131I-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the treatments. The superior growth inhibition achieved by 131I-chCE7 compared with 131I-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chCE7 with L1-CAM present in normal human tissues was investigated by direct binding of radioiodinated mAb to frozen tissue sections. Results showed a strong reaction with normal human brain tissue and weak but detectable binding to normal adult kidney sections. Seven patients with recurrent neuroblastoma were sequentially imaged with 131I-MIBG and 131I-chCE7. The results underlined the heterogeneity of neuroblastoma and showed the two imaging modalities to be complementary. 131I-chCE7 scintigraphy may have clinical utility in detecting metastases which do not accumulate 131I-MIBG, and the antibody may hold potential for radioimmunotherapy, either by itself or in combination with 131I-MIBG.

A comparison of targetting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients.

Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent (131)I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targetting ability in neuroblastoma patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG uptake and provide a relatively low number of 6,300 binding sites/cell for mAb chCE7. Tumours were treated with single injections of (131)I-MIBG (110 MBq) and with (131)I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with (131)I-chCE7, the subcutaneous tumours nearly disappeared; treatment with (131)I-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumour regrowth delay of 9 days occurred with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35, which does not bind to SK-N-SH cells, compared with a regrowth delay of 34 days with (131)I-mAb chCE7 and of 24 days with (131)I-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the treatments. The superior growth inhibition achieved by (131)I-chCE7 compared with (131)I-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chCE7 with L1-CAM present in normal human tissues was investigated by direct binding of radioiodinated mAb to frozen tissue sections. Results showed a strong reaction with normal human brain tissue and weak but detectable binding to normal adult kidney sections. Seven patients with recurrent neuroblastoma were sequentially imaged with (131)I-MIBG and (131)I-chCE7. The results underlined the heterogeneity of neuroblastoma and showed the two imaging modalities to be complementary. (131)I-chCE7 scintigraphy may have clinical utility in detecting metastases which do not accumulate (131)I-MIBG, and the antibody may hold potential for radioimmunotherapy, either by itself or in combination with (131)I-MIBG.

Targeting of meta-iodobenzylguanidine to SK-N-SH human neuroblastoma xenografts: tissue distribution, metabolism and therapeutic efficacy.

The clinical results of [(131)I]meta-iodobenzylguanidine (MIBG)-targeted radiotherapy in neuroblastoma patients is highly variable. To assess the therapeutic potential of [(131)I]MIBG, we used the SK-N-SH human neuroblastoma, xenografted in nude mice. The model was first characterized for basic parameters of MIBG handling in the host species. This demonstrated the presence of both strain- and nu/nu mutation-related differences in [(131)I]MIBG biodistribution. Fecal and urinary clearance rates of [(131)I]MIBG in mice roughly resemble those in humans, but mice metabolize MIBG more extensively. In both species, enzymatic deiodination in vivo was not an important metabolic route. Therapy with increasing [(131)I]MIBG doses (25-92 MBq) given as single i.v. injections resulted in proportionally increasing specific growth delay values (tumor regrowth delay/doubling time) of 1 to 5. Using gamma-camera scintigraphy for non-invasive dosimetry, the corresponding calculated absorbed tumor radiation doses ranged from 2 to 11 Gy. We also compared the therapeutic effects of a single [(131)I]MIBG administration with those resulting from a more protracted exposure by fractionating the dose in 2 to 6 injections or with high dose rate external-beam irradiation. No therapeutic advantage of a fractionated schedule was observed, and 5.5 Gy delivered by low dose-rate [(131)I]MIBG endo-irradiation was equi-effective with 5.0 Gy X-rays. The SK-N-SH neuroblastoma xenograft model thus appears suitable to evaluate possible treatment improvements to reach full potential of MIBG radiotherapy.

[(131)I] and [(125)I] metaiodobenzylguanidine therapy in macroscopic and microscopic tumors: a comparative study in SK-N-SH human neuroblastoma and PC12 rat pheochromocytoma xenografts.

[(131)I]Metaiodobenzylguanidine ([(131)I]MIBG) targeted radiotherapy is effective in debulking childhood neuroblastoma. The high-energy beta-emitter [(131)I]MIBG is, however, not very well suited to treat submillimeter tumors. The [(125)I]MIBG emission is more fully absorbed in small target volumes and therefore advocated for treatment of microscopic neuroblastoma. We investigated whether i.v. [(125)I]MIBG can have a therapeutic advantage over i.v. [(131)I]MIBG in realistic animal models. We used BALB/c nu/nu mice, bearing neuroadrenergic xenografts which differ in MIBG handling, i.e., extragranular vs. granular MIBG storage in the SK-N-SH human neuroblastoma and PC12 rat pheochromocytoma, respectively. Groups of 4-9 animals were treated with 10-100 MBq radioiodinated MIBG. Responses were calibrated against the effect of 4-5 Gy of external beam X-rays. SUBCUTANEOUS XENOGRAFTS: Due to the more extensive MIBG accumulation, the estimated MIBG exposure of the PC12 tumor was nearly 20-fold higher compared with the SK-N-SH xenograft which corresponded with a marked, i.e., nine-fold increased tumor growth delay after radioiodinated MIBG therapy. Both xenografts were equally sensitive to high-dose rate local irradiation. In neuroblastoma as well as pheochromocytoma, the therapeutic efficacy of [(131)I]MIBG was 6 times higher compared to the [(125)I]MIBG which is in reasonable agreement with the reported "131-I over 125-I" ratio of approximately 9 for the calculated absorbed radiation doses per unit of radioactivity. Apparently, the neuroblastoma was not relatively more sensitive to the (ultra)short range emitter [(125)I]MIBG than the pheochromocytoma, indicating that its therapeutic efficacy is independent of the intracellular MIBG storage mode. MICROSCOPIC TUMORS: The pheochromocytoma model consisted of widespread disease after i.v. cell injection with survival as endpoint. For the neuroblastoma, we induced focal intrahepatic microscopic tumors by intrasplenic injection and evaluated total liver weights 26 days after therapy. Theoretically, the therapeutic potential of [(125)I]MIBG at the cellular level should be at least as high as [(131)I]MIBG, but we failed to show any effect of [(125)I]MIBG therapy in both models. In contrast, measurable responses were obtained with [(131)I]MIBG, but these were lower than in the s.c. tumors when related to the responses induced by external X-rays. In conclusion, [(131)I]MIBG is decreasingly effective in microscopic disease and can therefore not be curative as a single agent. Our results strongly argue against the clinical use of [(125)I]MIBG and indicate that conventional total body irradiation was superior to [(131)I]MIBG for microscopic neuroblastoma. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 312-325 (2000).

Improved effect of 131I-MIBG treatment by predosing with non-radiolabeled MIBG in carcinoid patients, and studies in xenografted mice.

BACKGROUND: 131I-meta-iodobenzylguanidine (MIBG) has been used with success for the palliation of metastatic carcinoid. To qualify more patients for this treatment, we evaluated the effect of predosing with non-radiolabeled MIBG on 131I-MIBG tumour targeting in carcinoid patients and in mice with BON human carcinoid xenografts. PATIENTS AND METHODS: Ten carcinoid patients with a faint tumour imaging on a diagnostic 131I-MIBG scan (1 mCi = 37 MBq, 5 mg MIBG) received non-radiolabeled MIBG prior to a second scintigraphy. In case of improved tumour targeting patients were treated with 200 mCi (7.4 GBq) 131I-MIBG following a pharmacological predose of 20-40 mg/m2 MIBG. RESULTS: In six patients. highly increased 'tumour/non-tumour' ratios were seen due to reduced levels in normal tissues and increased tumour accumulation. The combined treatment applied in five patients, considerably improved symptoms in all (duration 6-12 months), accompanied by biochemical response in three. In BON carcinoid xenografted mice, MIBG was injected intraperitoneally followed by intravenous 125I-MIBG with similar findings: increased 'tumour/non-tumour' radioactivity ratios by 1.5-3-fold. CONCLUSION: Predosing with non-radiolabeled MIBG resulted in improved 131I-MIBG tumour targeting, prolonged palliation and encouragingly often biochemical responses in carcinoid.

[Carcinoid tumors of the intestines: developments in the Netherlands for diagnosis and palliative treatment]. / Carcinoïde tumoren van de darm: ontwikkelingen binnen Nederland in diagnostiek en palliatieve behandeling.

Carcinoid tumours in the intestine are slowly growing neuroendocrine tumours. Patients as a rule report symptoms of the carcinoid syndrome: attacks of diarrhoea and of flushing. When the earliest symptoms manifest themselves, metastases are already present, virtually always localized in the liver. At a late stage, heart failure may occur, difficult to treat and caused by fibrosis of the tricuspid valve in the presence of protractedly raised blood serotonin levels. To diagnose carcinoid tumours, use is made of radioactive substances binding to hormone receptors such as 131I-MIBG and 111-In-octreotide. When multiple metastases exist, only palliative treatment is possible. The drugs used are the somatostatin analog octreotide, interferon alpha, radioactive MIBG and non-radioactive MIBG; these drugs may also be used in combination. The therapies mentioned have approximately the same effect: symptoms improve in 60-80%, while 30-50% show a biochemical response, i.e. decrease of the number of breakdown products in the urine of the hormones produced by the tumour; tumour size decreases in 0-12%.

Bioavailability and toxicity after oral administration of m-iodobenzylguanidine (MIBG).

meta-iodobenzylguanidine (MIBG) radiolabelled with iodine-131 is used for diagnosis and treatment of neuroadrenergic neoplasms such as phaeochromocytoma and neuroblastoma. In addition, non-radiolabelled MIBG, administered i.v., is used in several clinical studies. These include palliation of the carcinoid syndrome, in which MIBG proved to be effective in 60% of the patients. Oral MIBG administration might be convenient to maintain palliation and possibly improve the percentage of responders. We have, therefore, investigated the feasibility of oral administration of MIBG in an animal model. Orally administered MIBG demonstrated a bioavailability of 59%, with a maximal tolerated dose of 60 mg kg(-1). The first and only toxicity encountered was a decrease in renal function, measured by a reduced clearance of [51Cr]EDTA and accompanied by histological tubular damage. Repeated MIBG administration of 40 mg kg(-1) for 5 sequential days or of 20 mg kg(-1) for two courses of 5 sequential days with a 2-day interval did not affect renal clearance and was not accompanied by histological abnormalities in kidney, stomach, intestines, liver, heart, lungs, thymus, salivary glands and testes. Because of a sufficient bioavailability in absence of gastrointestinal toxicity, MIBG is considered suitable for further clinical investigation of repeated oral administration in patients.

Chemical characterization and comparative cellular effects of meta-iodobenzyl guanidine and benzyl guanidine.

meta-Iodobenzyl guanidine (MIBG) combines the structural properties of the neuron-blocking agents bretylium and guanethidine and is being used increasingly for various clinical applications. Different samples of MIBG were assayed for possible contamination with benzyl guanidine (BG). Fast-atom-bombardment mass spectrometry (FAB-MS) analysis showed a prominent but variable m/z 150 signal, corresponding to a protonated BG. The MS/MS fragmentation pattern of these [M + H]+ ions was similar to that obtained from FAB-MS-generated, protonated BG, confirming the proposed molecule and associated structures. RP-HPLC analysis of both guanidines, however, excluded the possibility of contamination of MIBG with BG. It was therefore concluded that the BG signal was an artifact of the FAB-MS procedure. In addition, the importance of the meta-substituted iodine for the biological activity of MIBG was investigated. Three different biochemical and cell-biological properties of MIBG were compared with those of its precursor MIBA and BG. The assays used were: inhibition of the catecholamine "Uptake I" system in SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells, inhibition of mitochondrial respiration, and general cytotoxicity in L1210 leukemia cells. Of the drugs tested, MIBG was the most efficient in Uptake I inhibition and was more toxic in survival assays, but as compared with BG it was almost equipotent in inhibiting mitochondrial respiration. These findings contribute to a further elucidation of the mechanism by which MIBG exerts its various actions.

In vitro evaluation of N-(fluoro)isopropyl norephedrine as potential cardiac imaging agents for PET.

N-Isopropylnorephedrine (INE) and N-fluoroisopropylnorephedrine (FINE) were found to have a poor affinity for either beta-adrenoceptors and the norepinephrine carrier protein. The low affinity of both compounds for Uptake-1 is probably due to the introduction of a bulky substituent on the nitrogen atom. It is concluded that INE and FINE cannot be used for cardiac imaging with PET.

Meta-iodobenzylguanidine uptake in platelets, megakaryoblastic leukaemia cell lines MKPL-1 and CHRF-28-11 and erythroleukaemic cell line HEL.

The major toxicity encountered with [131I]-Meta-iodobenzylguanidine (MIBG) therapy in neuroblastoma patients is an often isolated thrombocytopenia. We believe that this results from MIBG-induced radiotoxicity of the megakaryocytes. Since it is difficult to obtain enough human megakaryocytes for uptake studies, we investigated whether the megakaryocytic cell lines, MKPL-1, CHRF-288-11 and HEL, are good models to study serotonin and MIBG accumulation in human megakaryocytes. Compared with platelets, low levels of specific MIBG accumulation (imipramine-sensitive) were shown in all cell lines, but that of serotonin was negligible in MKPL-1 and CHRF-288-11. Furthermore, the proportion of specific uptake of both MIBG and serotonin appeared greatest in the HEL cells. Although these cells seem to be good candidates to study serotonin and MIBG uptake, they are not a good model to investigate MIBG and serotonin accumulation in human megakaryocytes since they have no functional storage granules.

Uptake of the neuron-blocking agent meta-iodobenzylguanidine and serotonin by human platelets and neuro-adrenergic tumour cells.

The adrenomedulla-imaging agent meta-iodobenzylguanidine (MIBG) is concentrated by various tumours of neuroectodermal origin. Radio-iodinated [131I]MIBG is therefore increasingly used for diagnosis and therapy of these disorders. To study the cause of thrombocytopenia associated with [131I]MIBG therapy, we investigated the uptake of MIBG in human platelets in comparison with that of serotonin. Specific imipramine-sensitive uptake of [131I]MIBG was much slower than of [3H]serotonin, but after prolonged incubation high and serotonin-equivalent uptake levels were observed. Accumulation of MIBG saturated at 10- to 100-fold higher concentration than serotonin, and the affinity for uptake and intracellular storage in platelets was much higher for serotonin than for MIBG. Conversely, serotonin was not detectably concentrated by neuroadrenergic Uptake-I in SK-N-SH neuroblastoma and PC12 pheochromocytoma cells. Fluvoxamine inhibited the uptake of norepinephrine and MIBG in PC12 cells, similarly to that of serotonin in platelets. However, the drug was 100-fold more effective in inhibiting platelet transport of MIBG than of serotonin. The results indicate that MIBG uptake in platelets is not mediated by a neuro-adrenergic Uptake-I, but probably proceeds via the serotonin transport system. MIBG concentration by platelets was at least as efficient as in neuro-adrenergic tumour cells and has therefore (radio)biological potential for injuring these cells or precursor megakaryocytes. Platelet uptake of MIBG could be selectively blocked by fluvoxamine in concentrations which minimally affected its accumulation in neuro-adrenergic target cells.