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Biomedical subjects

H Bihl

Publications and source records attributed to H Bihl.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Somatostatin receptor scintigraphy in the primary diagnosis and follow-up care of gastrinoma].

Somatostatin receptor scintigraphy (SRS) was performed in 14 patients (five men, nine women; mean age 51.5 [20-71] years) with Zollinger-Ellison syndrome (ZES), a gastrinoma proven in 7 and suspected on clinical or biochemical grounds in 7. The results were compared with those obtained by other methods (ultrasound, computed tomography, angiography). All 12 known tumour manifestations were demonstrated by SRS in seven patients with histologically confirmed gastrinoma. In four patients previously non-localized tumour was revealed by SRS, while in seven other patients the procedure led to modification of the treatment (primary tumour resection: n = 3, resection of metastases: n = 2, percutaneous radiation or chemoembolization: one each). These results suggest the following indications for SRS: (1) staging or re-staging in histologically proven gastrinoma and (2) search for primary tumour in clinically and biochemically suspected ZES.

Adult↗
PubMed1994

Radioimmunotherapy with monoclonal antibodies. A new horizon in nuclear medicine therapy?

Radioimmunotherapy (RIT) with labeled tumor-associated monoclonal antibodies (MAbs) is a promising concept in oncology, which essentially consists of biological targeting of ionising radiation to tumors. Some encouraging clinical results have been achieved with RIT. However, there are severe problems associated with both understanding the mechanisms and predicting the effectiveness of RIT. This paper reviews the results of some major clinical trials, especially in malignant lymphomas and in some solid tumors. Furthermore, problems with RIT are described such as the significance of dose inhomogeneity and dose-rate effects, the appropriate dose calculation method, the toxicity of RIT and the development of HAMAs. It is suggested that newer technologies including chimeric antibodies, multiple-step targeting protocols, bone marrow transplantation, parallel application of external radiation, heat or bioreductive drugs will enable RIT to make an essential contribution to strategies for combating cancer.

Animals↗
PubMed1993

Improved visualization of carcinoid liver metastases by indium-111 pentetreotide scintigraphy following treatment with cold somatostatin analogue.

Five patients with hepatic metastases of midgut carcinoid underwent somatostatin receptor scintigraphy with indium-111 pentetreotide before and during treatment with octreotide. Octreotide treatment changed the biodistribution of 111In-pentetreotide significantly. Whereas the radioactivity in liver, spleen and kidney decreased, hepatic metastases showed increased contrast. In one patient, liver metastases could only be detected during octreotide treatment. These data suggest that the diagnostic reliability of somatostatin receptor scintigraphy in carcinoid liver metastases is not necessarily compromised by octreotide therapy. Because of different biodistributions, the detection of liver metastases may even be improved during octreotide therapy.

Carcinoid Tumor↗
PubMed1993

Monoclonal antibody accumulation in experimental and spontaneous lung metastases of human malignant melanoma in rodents.

Monoclonal antibody (mAb) uptake in metastatic lung lesions was depicted and evaluated by digital autoradiography. The models examined were experimental metastases of a human melanoma in nude mice and spontaneous metastases of human melanoma in immunocompromised young rats. By comparing uptake patterns in local (s.c.) tumours and in lung processes of various sizes it was found that patterns were essentially similar in both types of malignant tissue. From the point of view of visualization, however, the high blood content of lung tissue resulted in high background and low contrast. This could be overcome by the use of rapidly cleared antibody fragments.

Animals↗
PubMed1993

Monoclonal antibody uptake in B-cell lymphomas: experimental studies in nude mouse xenografts.

Accumulation of radiolabelled monoclonal antibodies (mAb) in human B-lymphoma xenografts was found to result in two distinct patterns. The basic elements leading to these patterns were elucidated by autoradiographic and immunohistological analysis applied to the nude mouse xenografts BJAB and OCI.LY1. With BJAB, accumulation occurred exclusively in peripheral cell layers of the lymphoma nodule, while central areas were not accessible irrespective of mAb dose. This feature was the consequence of an inefficient transport across intratumoral vessels together with peripheral mAb supply through a subcapsular pseudosinus. With OCI.LY1, intratumoral vessels showed generalized leakiness. Furthermore, interstitial transport was operative to a fair extent, such that in early images multiple sites of mAb extravasation were obvious, which coalesced during the course of prolonged uptake. The pattern of peripheral mAb uptake resulted in a low overall tumour uptake, while multifocal uptake yielded substantial accumulation values.

Animals↗
PubMed1993

[Somatostatin receptor scintigraphy. A new imaging procedure for the specific demonstration of carcinoids of the small intestine].

Scintigraphy with a radiolabelled somatostatin analog represents a new highly specific approach in the diagnostic work-up of receptor-positive APUD tumours and their metastases. We present our preliminary results with somatostatin receptor scintigraphy in 15 patients with histologically proven midgut carcinoid. 5 out of 6 primary tumour sites (83%) and 90% of the known metastatic lesions could be detected; unknown metastatic lesions were seen in 5 patients. Compared with other nuclear medicine procedures somatostatin receptor scintigraphy is able to detect all tumour sites within hours. This advantage will promote the acceptance of this sensitive and specific imaging modality by the clinicians with regard to preoperative work-up and symptomatic therapy with a somatostatin analog.

Adult↗
PubMed1993

The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma.

In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with 111Inpentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group.

Adult↗
PubMed1993

Comparison of systemic radiotherapy with I-131-labeled monoclonal antibody BW575/9 to external beam radiotherapy in human neuroblastoma xenografts.

The therapeutic effectiveness of external beam radiotherapy (XRT) and radioimmunotherapy (RIT) was investigated in a human neuroblastoma (SK-N-SH) xenotransplanted to nude mice. This tumor model seems especially suitable for comparison of the relative biological effectiveness of RIT vs. XRT, as--in contrast to most tumor models--it shows an unusually homogenous uptake of the labeled MAb, thus providing a homogenous intratumoral dose distribution. XRT was performed using single fractions of 800, 1600, 2000 and 2400 cGy and RIT was delivered by intravenous injection of 15, 19 and 26 MBq of the I-131-labeled monoclonal antibody (MAb) BW575/9. Therapeutic efficiency of the two radiation modalities was assessed in terms of tumor volume doubling time (VDT). Miniature thermoluminescent (mini-TLD) dosimetry and MIRD-based dose calculations were used to evaluate the absorbed doses delivered by RIT and to assess the degree of homogeneity of the dose distribution. RIT with 19 MBq of the I-131 BW575/9 delivered a tumor dose of 2820 cGy measured by TLD and resulted in a tumor VDT of 32 days (vs. one day in controls). An equivalent effect on VDT was achieved by a single fraction XRT of 1600 cGy. The relative efficiency of XRT compared with RIT (ratio of dose XRT/dose RIT required to give the same VDT) was 0.57. Application of 26 MBq of the MAb (= 3200 cGy) resulted in complete tumor regression after ten days as did XRT with 2400 cGy, corresponding to a relative efficiency of 0.75.

Animals↗
PubMed1993

[Systemic radiotherapy using monoclonal antibodies. Options and problems].

Radiolabeled monoclonal antibodies (MAbs), by virtue of their tumor specificity, offer the prospect of localized, highly targeted radiation treatment of malignant tumors. To date, a large number of radioimmunotherapy (RIT) studies have been reported in experimental and clinical settings showing the potential of this therapeutic strategy. This includes RIT-trials in hepatoma, cholangiocarcinoma, ovarian carcinoma, brain tumors, melanoma, neuroblastoma and especially Hodgkin's and non-Hodgkin's lymphomas. Despite very promising results in some of these studies, radioimmunotherapy is currently still in a developmental status. Selective accumulation of MAbs at tumor sites-a prerequisite for effective radioimmunotherapy-is a complex process. Many factors such as antigen heterogeneity, distinct antibody features (affinity, subclass, fragment size, etc.), labeling techniques, tumor physiology and competing antigens were identified in the last years using theoretical and experimental tumor models. Strategies to improve these critical parameters are currently under investigation in order to increase the efficacy of radioimmunotherapy.

Female↗
PubMed1993

Biodistribution of 111In-pentetreotide and dosimetric considerations with respect to somatostatin receptor expressing tumor burden.

The general features of the biodistribution of the labeled somatostatin analog 111In-pentetreotide are already known. We describe some details of 111In-pentetreotide accumulation in the thyroid gland, mammae, spleen and gastrointestinal tract with respect to endocrine parameters, kinetics and time of imaging. In addition, dose estimations were performed for liver, spleen and kidney in patients without neuroendocrine tumor load and in patients with large tumors positive for somatostatin receptors. The overall absorbed dose turned out to be within the range reported previously. However, in patients with extensive tumor burden the radiation dose in liver, spleen and kidney tended to be lower than in patients without such malignancy. The dependence of estimated organ doses on the presence of somatostatin receptor-expressing tumors will have to be considered if radiotherapy with suitable labeled somatostatin analogs becomes available.

Biomarkers, Tumor↗
PubMed1993

Diagnostic reliability of somatostatin receptor scintigraphy during continuous treatment with different somatostatin analogs.

In order to evaluate the diagnostic reliability of somatostatin receptor scintigraphy (SRS) in patients treated with somatostatin analogs, ten patients with metastatic neuroendocrine tumors were investigated before and during continuous treatment. Different somatostatin analogs were used for therapy: five patients received octreotide (Sandostatin, Sandoz, Switzerland) and five were treated with BIM 23014 (Lanreotide, Ipsen Biotech, France) within the scope of a clinical phase II study. The SRS findings were analyzed in terms of biodistribution of the labeled somatostatin analog and tumor visualization comparing the two studies in each patient. Whereas liver, spleen, and kidney uptake were decreased during octreotide treatment and increased on lanreotide therapy, tumor accumulation was intensified in all but one patient. Our results suggest that the diagnostic value of SRS is not necessarily restricted during treatment with somatostatin analogs. Indeed, tumor visualization may even be enhanced in this therapeutic setting.

Adult↗
PubMed1993

Somatostatin receptor scintigraphy and magnetic resonance imaging in recurrent medullary thyroid carcinoma: a comparative study.

In a prospective study, 18 patients with recurrent medullary thyroid carcinoma (MTC) underwent magnetic resonance imaging (MRI) of the neck and mediastinum and somatostatin receptor scintigraphy (SRS) with 111In-labeled pentetreotide. In nine patients with macroscopic MTC, 17 corresponding lesions were found on MRI and SRS; in addition, 13 suspicious lesions were seen on SRS only. Histological confirmation was available for 19 metastatic lesions, showing MRI to be true positive in 13 metastases, SRS in 18. In minimal residual disease (n = 10), MRI and SRS were compared with the histological findings in three patients and with selective venous catheterization (SVC) in seven patients. Corresponding findings on MRI and SVC were seen in one of seven, whereas SRS and SVC showed concordant localization of tumor recurrence in five of seven. Histological examination demonstrated MTC tissue in one of three cases; MRI and SRS were false positive in one of three cases, while in the others the interpretation remained uncertain. In conclusion, SRS is a promising imaging modality for localization of MTC recurrence. MRI provides better spatial resolution and thus facilitates the planning of surgery for macroscopic metastases. In minimal residual disease, SRS turned out to be superior in detecting occult MTC recurrence, confirming SVC findings.

Adolescent↗
PubMed1993

Systemic radiotherapy with monoclonal antibodies. An experimental study with human neuroblastoma xenografts in nude mice.

In this experimental study, feasibility and efficiency of systemic radiotherapy with the I-131 labelled monoclonal antibody BW575/9 (radioimmunotherapy) are investigated using human SK-N-SH neuroblastoma transplanted into nude mice. Series of six nude mice were treated with intravenous application of 400 microCi (group 1), 700 microCi (group 2) of the I-131 labelled and of the unlabelled MAb (group 3). An untreated group (group 4) served as control. Tumors of group (3) and (4) showed an identical growth. In group (1), tumor growth was arrested for seven days. In group (2), the tumor showed complete regression after eight days which lasted for 55 days. Thereafter, the tumor started to regrow. This growth characteristics are correlated with the doses achieved in the tumor using a medical internal radiation dose (MIRD) formulation. The biodistribution data necessary for MIRD calculation were obtained by previously performed experiments with the I-125 labelled MAb. The doses assessed in the tumor turned out to be five to ten times greater than those in normal tissues (liver, bone, etc.) These results confirm feasibility, selectivity and efficiency of radioimmunotherapy in the above described model. Moreover, this in vivo model seems suitable for further investigations concerning fundamental issues of radioimmunotherapy.

Animals↗
PubMed1992

Late cervical lymph node recurrence in differentiated thyroid carcinoma. An inherent problem of 131I beta dose distribution in small tumor deposits?

In differentiated thyroid carcinoma, postoperative radioiodine therapy is an undisputed element of the integral therapeutic concept. Sometimes, however, and years after initial diagnosis and therapy, cervical lymph node metastases occur without any evidence of local relapse or distant metastases, indicating that radioiodine therapy has not achieved definite tumor cell sterilization. A Monte Carlo computer simulation of the spatial energy dose distribution of 131I in small functioning tumor manifestations was performed to explain this phenomenon. It appeared that only a small fraction of the total beta-energy dose can be deposited inside the tumor if the latter becomes smaller than 1 mm in diameter: for tumors with homogeneous 131I uptake and diameters of 1.0, 0.5, 0.2, 0.1, 0.05 and 0.02 mm, this value does not exceed 86, 73, 39, 16, 8 and 4%, respectively. These data suggest a potential therapeutic gap for small tumor manifestations not apparent at the time of initial diagnosis and could explain the occasional occurrence of late cervical lymph node metastases.

Combined Modality Therapy↗