Daniel Kahn

Radioimmunoscintigraphy with In-111-labeled capromab pendetide predicts prostate cancer response to salvage radiotherapy after failed radical prostatectomy

PURPOSEnWe investigated the ability of In-111-capromab pendetide to separate patients who have failed radical prostatectomy into categories of those who would versus those who would not respond to salvage radiotherapy.nnnMETHODSnProstate-specific antigen (PSA) levels in 32 men with prostate cancer who had failed radical prostatectomy and had undergone a whole-body In-111-capromab pendetide scan were followed-up for 13 months (median) after salvage radiotherapy to the pelvis. A logistic regression model was used to determine whether the scan findings, as well as other clinical variables, were associated with a durable complete response (DCR), a nondurable response (NDR), or no response (NR).nnnRESULTSnSixteen of 23 (70%) men with a normal scan outside the prostatic fossa achieved a DCR after salvage radiotherapy versus two of nine (22%) who had a positive scan outside the prostate fossa and pelvis (P = .0225, Fishers exact test). Predicted probability (95% confidence interval [CI]) that a DCR would be obtained with a normal scan was 0.88 (0.55 to 0.98); for men with a positive scan limited to the prostatic fossa it was 0.62 (0.42 to 0.79); and for men with a positive scan outside the pelvis it was 0.27 (0.09 to 0.58). No other variables before radiotherapy showed a significant association with the DCR rate.nnnCONCLUSIONnSalvage radiotherapy is statistically more likely to lead to a durable complete PSA response in men with prostate cancer who have failed radical prostatectomy and have a negative In-111-capromab pendetide scan outside the pelvis as compared with those who have a positive scan.

Radioimmunoscintigraphy with 111Indium Labeled Cyt-356 for the Detection of Occult Prostate Cancer Recurrence

We assessed the safety and ability of the 111indium labeled immunoconjugate 7E11-C5.3-glycyl-tyrosyl-(N,e-diethylenetriaminepentaacetic acid)-lysine (CYT-356) to detect sites of occult prostate cancer in 27 subjects who had undergone radical prostatectomy and whose only evidence of recurrent disease was an increasing (0.8 ng./ml. or greater) serum prostate specific antigen (PSA). All subjects underwent whole body scintigraphy between 2 and 4 days following the radiopharmaceutical injection. Routine blood work and human anti-mouse antibody titers were monitored. Scintigraphic findings were compared with clinical parameters, prostatic fossa biopsy results and conventional imaging techniques. Except for transient hypotension in 1 subject following the second infusion, no side effects or human anti-mouse antibody titers were detected. In 22 subjects 1 or more lesions were detected, of which 11 (50%) were confirmed by biopsy, computerized tomography or magnetic resonance imaging. Of 14 subjects with lesions in the prostatic fossa 13 had biopsies performed, 8 (62%) of which were positive. Magnetic resonance imaging confirmed tumor in the spine and chest computerized tomography findings were compatible with lesions seen in the mediastinum in 1 subject each. There was a statistically significant relationship between detecting a scan abnormality and the initial pathological stage of disease but not with the serum PSA. These data provide preliminary evidence that 111indium labeled CYT-356 can be safely administered and readministered, and it detects sites of occult prostate cancer recurrence in subjects whose PSA is increasing following radical prostatectomy.

Evaluation of various corrections to the standardized uptake value for diagnosis of pulmonary malignancy.

Objective Standard uptake values (SUVs) are widely used for quantifying the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours. The objective of this study was to evaluate the accuracy of SUVs for malignancy in lung nodules/masses and to analyse the effects of tumour size, blood glucose levels and different body weight corrections on SUV. Methods One hundred and twenty-seven patients with suspicious lung lesions imaged with 18F-FDG positron emission tomography (PET) were studied retrospectively. Pathology results were used to establish lesion diagnosis in all cases. SUVs based on maximum pixel values were obtained by placing regions of interest around the focus of abnormal 18F-FDG uptake in the lungs. The SUVs were calculated using the following normalizations: body weight (BW), lean body weight (LBW), scaled body surface area (BSA), blood glucose level (Glu) and tumour size (Tsize). Receivers operating characteristic (ROC) curves were generated to compare the accuracy of different methods of SUV calculation. Results The areas under the ROC curves for SUVBW, SUVBW+Glu, SUVLBW, SUVLBW+Glu, SUVBSA, SUVBSA+Glu and SUVBW+Tsize were 0.915, 0.912, 0.911, 0.912, 0.916, 0.909 and 0.864, respectively. Conclusion The accuracy of SUV analysis for malignancy in lung nodules/masses is not improved by correction for blood glucose or tumour size or by normalizing for body surface area or lean body weight instead of body weight.

Effects of Intravenous Amino Acid Administration with Y-90 DOTA-Phe1-Tyr3-Octreotide (SMT487[OctreoTher™]) Treatment

Y-90-DOTA-Phe1-Tyr3-Octreotide (90Y-SMT 487, OctreoTher) has shown potential for effectively treating patients with neuroendocrine tumors. The dose-limiting organ for this agent is the kidney. The purpose of this work is to assess the effectiveness of a commercially available amino acid solution on reducing renal uptake of 90Y-SMT 487 and determine the safety profile of this solution. Subjects with In-111 pentetreotide positive tumors and normal creatinine levels were treated with 3 cycles of 90Y-SMT 487, 120 mCi/cycle, at 6-9 week intervals. During each treatment two liters of an amino acid solution containing arginine and lysine (Aminosyn II 7%, Abbott Laboratories, Abbott Park, IL) were infused IV over 4 hours. Adverse events were recorded. To assess the effect of Aminosyn II on renal uptake of 90Y-SMT 487, a subgroup of subjects underwent bremsstrahlung imaging 24 hours following infusion. Kidney to liver (K/L) count density ratios were generated from the baseline In-111 pentetreotide images (performed without amino acid infusion) and the 90Y bremsstrahlung images. Follow-up creatinine levels were obtained. Thirty-seven subjects received a total of 89 90Y-SMT 487 treatments. The number of amino-acid infusions associated with one or more episodes of emesis was 53 (62%). During 13 (15%) of these infusions, the Aminosyn II rate had to be reduced because of severe nausea and vomiting. Symptomatic flushing occurred during 16 (18%) of the infusions. One subject experienced a near syncopal event shortly after completing the infusion. Creatinine levels remained normal in 34 of 36 subjects during a mean follow-up period of 9.8 months. Fourteen subjects underwent bremsstrahlung imaging following infusion of 90Y-SMT 487. Kidney uptake appeared to decrease with administration of the amino acid solution in 13 of 14 subjects. For the 28 individual kidneys, the mean percent decrease in the Kidney/Liver uptake ratio with the amino acid solution was found to be 32%. We conclude that 2 L of Aminosyn II 7% infused over 4 hours appears to notably reduce renal uptake of 90Y-SMT 487. Aminosyn is generally well tolerated, particularly at lower infusion rates with occasional moderate to severe nausea and vomiting at higher rates.

Enhanced uptake of 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone treatment: potential for increasing delivery of therapeutic agents.

Following androgen ablation therapy, skeletal metastases from prostate cancer appear in some instances to show an increase in 99Tcm-methylene diphosphonate (99Tcm-MDP) uptake. Such a phenomenon could represent a mechanism to increase delivery of bone-seeking therapeutic agents to skeletal metastatic sites. The aim of this study was to characterize more precisely the potential increase in 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone therapy. Baseline bone scans were performed within 1 week of onset of hormone therapy in patients with stage D2 prostate cancer followed by multiple repeat bone scans for up to 4-6 weeks. The count density within metastatic lesions was divided by the average count density from several areas of normal bone to obtain a lesion to normal bone uptake ratio (L/N) for each lesion in each scan. Altogether, 61 skeletal metastases were identified on bone scans from five subjects. Eighty-four percent (51/61) of these lesions showed an increase in 99Tcm-MDP activity relative to normal bone following initiation of hormone therapy with a mean peak increase of 39%. Thirty-nine of these 51 metastatic lesions showed maximum uptake at 3 weeks post-onset of hormone treatment. From our findings, it appears that approximately 3 weeks following initiation of hormone blockade, most skeletal metastases from prostate cancer will demonstrate significantly enhanced 99Tcm uptake relative to normal bone. Consequently, it may be possible to improve the uptake and effectiveness of therapeutic bone-seeking radiopharmaceuticals by administering these agents following hormone therapy in patients with prostate cancer metastases.

Crossed cerebellar diaschisis associated with balloon test occlusion of the carotid artery

99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomographic (SPECT) brain imaging performed in conjunction with balloon test occlusion of the carotid artery has been used to assess risk of neurologic sequelae that might follow permanent surgical ligation of the artery. The predictive value of cortical hypoperfusion during temporary carotid occlusion for adverse neurologic events has been debated in previous publications. We believe that the risk of an adverse event is greater when a reduction in cortical perfusion during balloon test occlusion is associated with crossed cerebellar diaschisis (CCD). To test our hypothesis we evaluated the results of 27 99Tcm-HMPAO SPECT brain studies obtained in association with balloon test occlusions of the carotid artery. In each case we correlated clinical outcome with the presence or absence of regional decreases in cerebral perfusion and CCD. All of the 27 patients were free of neurologic symptoms during the balloon test occlusion. Seventeen of the 27 scintigraphic studies were felt to be abnormal, showing cortical perfusion defects all on the side of the occlusion. Among these 17 patients, five demonstrated CCD. Four of these five CCD patients showed evidence for cerebral cortical ischaemia on the side of the temporary carotid occlusion either shortly after the procedure or following carotid artery sacrifice. Of the remaining 12 patients with regionally reduced cerebral perfusion and no CCD, none showed evidence for cortical ischaemia in association with balloon test occlusion, and five of these 12 patients had carotid ligation without subsequent neurologic sequelae. Our results provide evidence to support our hypothesis that when CCD accompanies regional hypoperfusion on a brain SPECT study obtained after injection of 99Tcm-HMPAO during balloon test occlusion of the carotid artery, the patient is likely to be at increased risk of adverse neurologic sequelae following carotid sacrifice.

Captopril-enhanced 99tcm-mag3 renal scintigraphy in subjects with suspected renovascular hypertension

This pilot study was undertaken to generate preliminary data on the accuracy of captopril-enhanced renal scintigraphy with a relatively new radiopharmaceutical, 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) for detecting significant renal artery stenosis. Truth data was based either on arteriographic or outcome criteria (blood pressure response to therapy). Twenty-seven subjects with suspected renovascular hypertension were studied with baseline and captopril-enhanced 99Tcm-MAG3 renal scintigraphy and renal arteriography. Scan interpretations were expressed as a probability of a significant renal artery stenosis. Scan interpretations were compared with renal arteriographic results, renal vein renin levels, blood pressure values after renal artery repair, and blood pressure control after 4–26 months of clinical follow-up. Using ≥50% luminal obstruction on arteriography as the reference standard for renal artery stenosis and a high probability scan representing a positive test, the test sensitivity and specificity were 33 and 97%, respectively (using high or indeterminate probability to represent a positive scan, the test sensitivity and specificity were 67 and 83%, respectively). The negative predictive value of a low probability scan for renal artery stenosis was 80%. However, including a measure of renovascular hypertension (blood pressure response to renal artery repair) as the reference standard, the accuracy of the scan improves, with the negative predictive value of a low probability scan for renovascular hypertension increasing to 97%. Scintigraphic results were also positively correlated with renal vein renin values in a statistically significant fashion (two-tailed Fisher exact test statistic = 6.43, P=0.0219). Captopril-enhanced 99Tcm-MAG3 renal scintigraphy is a moderately accurate technique for detecting renal artery stenosis. More importantly, our preliminary findings suggest that the scintigraphic technique using 99Tcm-MAG3 appears to predict the blood pressure response to renal artery repair in subjects with suspected renovascular hypertension, thereby separating subjects with haemodynamically insignificant renal artery stenosis from those with renovascular hypertension.

Incidental Meningioma Detected on 18F-Fluoride With PET/CT During Initial Staging for Prostate Cancer.

A 72-year-old man with recently diagnosed high-grade prostate adenocarcinoma with a Gleason score of 7 and PSA of 3.7 underwent ¹⁸F-fluoride PET/CT bone scan. The ¹⁸F-fluoride PET/CT bone scan showed increased uptake in the brain in the right frontal lobe. The follow-up MRI revealed a right frontal meningioma.

Samarium-153-EDTMP in the treatment of refractory rheumatoid arthritis

We examined the preliminary safety and efficacy of intravenous samarium-153-EDTMP (Sm-153) in the treatment of refractory rheumatoid arthritis (RA). In an open-label sequential group comparison of 0.5, 1.0, and 2.0 mCi/kg, Sm-153 was administered as a single intravenous infusion to 24 patients with refractory disease. Across treatment doses, the frequency of American College of Rheumatology (ACR) 20% responses was 25%, 29%, 25%, and 33% at 2, 4, 8, and 12 weeks, respectively. Expected significant declines in absolute neutrophil count, hemoglobin, and platelet counts were observed with nadirs seen between 2&4 weeks. Sm-153, at doses of 0.5 and 1.0 mCi/kg, is well tolerated but minimally effective in the treatment of refractory RA as measured using ACR response criteria.We examined the preliminary safety and efficacy of intravenous samarium-153-EDTMP (Sm-153) in the treatment of refractory rheumatoid arthritis (RA). In an open-label sequential group comparison of 0.5, 1.0, and 2.0 mCi/kg, Sm-153 was administered as a single intravenous infusion to 24 patients with refractory disease. Across treatment doses, the frequency of American College of Rheumatology (ACR) 20% responses was 25%, 29%, 25%, and 33% at 2, 4, 8, and 12 weeks, respectively. Expected significant declines in absolute neutrophil count, hemoglobin, and platelet counts were observed with nadirs seen between 2-4 weeks. Sm-153, at doses of 0.5 and 1.0 mCi/kg, is well tolerated but minimally effective in the treatment of refractory RA as measured using ACR response criteria.