A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3-5 days later by 100-150 micrograms of indium-111 streptavidin, at the specific activity of 280-370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1-8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1-30:1) and 45:1 (range 12:1-120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1-30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01-0.3) for recurrences and 0.05 for primary tumour (range 0.005-0.2). Over 24-48 h 14% i.d. (range 8-18% i.d.) was found in the urine, 14% i.d. (range 6-29% i.d.) in the blood and 63% i.d. (range 56-70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer.

Positron emission tomography/computed tomography (PET/CT) with 11C-choline is an established diagnostic tool for restaging prostate cancer patients with biochemical failure after primary treatment. In the present case, 11C-choline PET/CT was performed in a prostate cancer patient with skeletal metastases, treated with hormonal therapy. In addition to the detection of pathologic uptake at prostate and vertebra, 11C-choline uptake occurred in the neck. The finding was suggestive for a parathyroid adenoma on subsequent ultrasound, then finally confirmed by parathyroid scintigraphy and histopathological analysis performed after hemithyroidectomy.

Synovial metaplasia was seen in the capsular tissue from both types of implant, but more so from capsules surrounding polyurethane implants more than 5 years old. The density and orientation of the collagen fibers and the foreign body reaction were very similar for the two types of implant.

The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24-36 h, 5 mg avidin Was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15-20 mCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection.[99mTc]PnAO-biotin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1-2 h after the administration of [99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti-tenascin MoAb BC2, avidin and [99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.

A method was set up for single-photon emission tomographic (SPET) quantification of radioactivity concentration in small anatomical structures. The method is based on the theoretical model proposed by Kessler et al. (J. Comput Assist Tomogr 1984; 8: 514-522) describing the effects of spatial resolution (partial volume effect and spillover) on the quantification of radioactivity concentration in small spherical objects. The model was validated here in SPET, by phantom experimental measurements, in relation to object size and source/background contrast. Good agreement was found between model-predicted and SPET-measured radioactivity concentration ratios in hot spots in hot background experiments. Accuracy of the method was assessed for comparison of model-corrected and true radioactivity concentration ratios and was found to be within 8.5% over the full range of object size (9.4-36.5 mm). The good agreement found indicates that the model can be used to correct for partial volume effect and spillover in specific clinical situations, when the anatomical structure under study can be approximated by a sphere of known size (e.g. neuroreceptor and tumour studies). The method was applied to a representative SPET monoclonal antibody patient study for the quantification of radioactivity concentration in ocular melanoma.

Diagnosis and experimental therapy of cancer have been performed with encouraging results using radiolabelled monoclonal antibodies. However, the high background due to non-specific uptake by normal tissue and blood is a major drawback in antibody-guided tumor detection. Various strategies have been proposed to overcome this problem, such as computed background subtraction, use of a second antibody, and local delivery. An antibody is a slow "bullet" for tumor targeting, since in many lesions it requires two or three days to accumulate. The use of fragments such as F(ab')2 or Fab, which display a faster blood clearance than whole antibody, improves tumor localization to a sufficient extent (hours) to allow the use of the most suitable radionuclides, e.g. 99m-Tc. In therapeutic applications we are still far away from the optimal condition in terms of the absolute amount of radioactivity delivered to the tumor. The high specificity of antibodies could be exploited at its best by delaying the delivery of the label to a time when the ratio tumor-bound to non-tumor-bound antibody has reached its maximum value. To obtain this goal, the label should display a fast clearance and should be captured by the antibody already targeted onto tumor cells. These considerations have led to strategies of tumor pretargeting where antibody and label are administered separately. One of these strategies, based on the avidin-biotin system, has already been used extensively for several years in immunohistochemistry and in ELISA. Due to the flexibility of this system, several alternative protocols are possible.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent 68Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing 68Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with 68Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, 68Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by 68Ga-PSMA, and 68Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase.

Summary To evaluate the use of pretargeted immunoscintigraphy (ISG) in the diagnosis and follow-up of patients with medullary thyroid carcinoma (MTC), we studied 25 patients with histologically proven disease; ISG was repeated after surgery in two patients. The antibody, either an anticarcinoembryonic antigen (CEA) or an antichromogranin A (CgA) biotinylated monoclonal antibody (MAb) or a cocktail of the two biotinylated MAbs was first injected. After 24 h, avidin was administrated i.v., followed by "'In-labelled biotin 24 h later. Fifty-two lesions were visualised. Six primary tumours, diagnosed by increased calcitonin levels, were all correctly diagnosed; 47 recurrences, also suspected by blood tumour markers, were detected and confirmed by cytology or histology. In one case, single photon emission tomography allowed the detection of small lymph nodes with a diameter of 4 -7 mm. These lesions, not judged neoplastic by ultrasound, were confirmed to be neoplastic by fine needle aspiration. Pretargeted ISG correctly localises primary tumours and recurrences in MTC patients, when the only marker of relapse is serum elevation of calcitonin. With this three-step pretargeting method, cocktails of potentially useful MAbs can be used, avoiding false-negative studies that may occur when CEA or CgA are not expressed.Keywords: medullary thyroid carcinoma; monoclonal antibody; avidin-biotin Medullary thyroid carcinoma (MTC) arises from calcitoninsecreting parafollicular cells in the thyroid. Both the sporadic and the familial form are treated by surgery (Chong et al., 1975;Rossi et al., 1980), as the efficacy of radiotherapy is limited (Samaan et al., 1988) and chemotherapy is ineffective (Rougier et al., 1983;Brunt and Wells, 1987). Early diagnosis of recurrence or metastasis and accurate localisation of recurrent disease are very important prerequisites for successful surgical excision.Elevated serum calcitonin (Ct) is considered to be a marker for MTC. High serum levels of Ct and carcinoembryonic antigen (CEA) can often be found in patients with recurrent disease several years before it becomes clinically apparent, but, at present, no efficient and specific method is available for the localisation of recurrences.Morphological imaging techniques (ultrasonography, US; computerised tomography, CT; magnetic resonance imaging, MRI) are routinely used to confirm and localise a biologically detected recurrence but are not always adequate because of topographic polymorphism and the small size of tumour recurrences at an early stage of development (Schwerk et al., 1985;Frank et al., 1987;Crow et al., 1989).Several methods based on tumour avidity of non-specific radiopharmaceuticals such as [99"Tc](V)DMSA, '3I11231-MIBG and 20'T1 have also been designed for this purpose, with variable results (Arnstein et al., 1986;Hilditch et al., 1986;Baulieu et al., 1987;Clarke et al., 1987;Hilditch, 1987; Clarke et al., 1988;Hoefnagel et al., 1988;Guerra et al., 1989;Adams et al., 1990;Charkes et al., 1990;Udelsman et al., 1993).In the attem...